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Sample records for aged non-human primates

  1. 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

  2. Impaired fasting blood glucose is associated to cognitive impairment and cerebral atrophy in middle-aged non-human primates

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    Djelti, Fathia; Dhenain, Marc; Terrien, Jérémy; Picq, Jean-Luc; Hardy, Isabelle; Champeval, Delphine; Perret, Martine; Schenker, Esther; Epelbaum, Jacques; Aujard, Fabienne

    2017-01-01

    Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper normal range are associated with memory impairment and cerebral atrophy. Due to a close evolutional similarity to Man, non-human primates may be useful to investigate the relationships between glucose homeostasis, cognitive deficits and structural brain alterations. In the grey mouse lemur, Microcebus murinus, spatial memory deficits have been associated with age and cerebral atrophy but the origin of these alterations have not been clearly identified. Herein, we showed that, on 28 female grey mouse lemurs (age range 2.4-6.1 years-old), age correlated with impaired fasting blood glucose (rs=0.37) but not with impaired glucose tolerance or insulin resistance. In middle-aged animals (4.1-6.1 years-old), fasting blood glucose was inversely and closely linked with spatial memory performance (rs=0.56) and hippocampus (rs=−0.62) or septum (rs=−0.55) volumes. These findings corroborate observations in humans and further support the grey mouse lemur as a natural model to unravel mechanisms which link impaired glucose homeostasis, brain atrophy and cognitive processes. PMID:28039490

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

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    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.

  4. Calorie restriction and resveratrol supplementation prevent age-related DNA and RNA oxidative damage in a non-human primate.

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    Marchal, J; Dal-Pan, A; Epelbaum, J; Blanc, S; Mueller, S; Wittig Kieffer, M; Metzger, F; Aujard, F

    2013-09-01

    Oxidative stress is a key factor in the aging process and in the development of age-related diseases. Because nutritional interventions such as caloric restriction (CR) delay the onset of age-related diseases and increase the lifespan of many species, the impact of a moderate CR was tested on male grey mouse lemur (Microcebus murinus), which have a median survival time of 5.7 years in captivity. The effects of CR on these lemurs were compared with a potential mimetic, resveratrol (RSV), a polyphenol naturally found in grapes. We hypothesized that both CR and RSV impact oxidative DNA and RNA damage compared to standard-fed control (CTL) animals. Adult (3-4 years old) male mouse lemurs were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day(-1)·kg(-1)). Oxidative stress was estimated after 3, 9, 15 and 21 months of treatment using the measurement of oxidized nucleosides in urine samples by mass spectrometry. The resting metabolic rate, adjusted for changes in body composition, was also measured to assess the potential relationship between oxygen consumption and oxidative damage markers. This study provides evidence for oxidative stress accumulation with age in grey mouse lemur. Dietary interventions resulted in a short-term increase in oxidative stress levels followed by reduced levels with increasing age. Moreover, in this photoperiod-dependent heterotherm primate, seasonal variations in oxidative stress were observed, which was likely due to a season-dependent, cost-benefit trade-off between torpor use and oxidative stress.

  5. 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.

  6. 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.

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

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    Liebal, Katja; Call, Josep

    2012-01-12

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

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

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    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.

  9. 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.

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

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    Shrewsbury, Marvin

    2003-04-01

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

  11. Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus.

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    Dal-Pan, Alexandre; Terrien, Jérémy; Pifferi, Fabien; Botalla, Roger; Hardy, Isabelle; Marchal, Julia; Zahariev, Alexandre; Chery, Isabelle; Zizzari, Philippe; Perret, Martine; Picq, Jean Luc; Epelbaum, Jacques; Blanc, Stéphane; Aujard, Fabienne

    2011-03-01

    A life-long follow-up of physiological and behavioural functions was initiated in 38-month-old mouse lemurs (Microcebus murinus) to test whether caloric restriction (CR) or a potential mimetic compound, resveratrol (RSV), can delay the ageing process and the onset of age-related diseases. Based on their potential survival of 12 years, mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake and a RSV group (200 mg/kg.day(-1)) fed ad libitum. Since this prosimian primate exhibits a marked annual rhythm in body mass gain during winter, animals were tested throughout the year to assess body composition, daily energy expenditure (DEE), resting metabolic rate (RMR), physical activity and hormonal levels. After 1 year, all mouse lemurs seemed in good health. CR animals showed a significantly decreased body mass compared with the other groups during long day period only. CR or RSV treatments did not affect body composition. CR induced a decrease in DEE without changes in RMR, whereas RSV induced a concomitant increase in DEE and RMR without any obvious modification of locomotor activity in both groups. Hormonal levels remained similar in each group. In summary, after 1 year of treatment CR and RSV induced differential metabolic responses but animals successfully acclimated to their imposed diets. The RESTRIKAL study can now be safely undertaken on a long-term basis to determine whether age-associated alterations in mouse lemurs are delayed with CR and if RSV can mimic these effects.

  12. High reinforcing efficacy of nicotine in non-human primates.

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    Bernard Le Foll

    Full Text Available Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine's role in reinforcing tobacco smoking. Because of ethical difficulties in inducing nicotine dependence in naïve human subjects, we explored reinforcing effects of nicotine in experimentally-naive non-human primates given access to nicotine for periods of time up to two years. Five squirrel monkeys with no experimental history were allowed to intravenously self-administer nicotine by pressing one of two levers. The number of presses on the active lever needed to obtain each injection was fixed (fixed-ratio schedule or increased progressively with successive injections during the session (progressive-ratio schedule, allowing evaluation of both reinforcing and motivational effects of nicotine under conditions of increasing response cost. Over time, a progressive shift toward high rates of responding on the active lever, but not the inactive lever, developed. The monkeys' behavior was clearly directed toward nicotine self-administration, rather than presentation of environmental stimuli associated with nicotine injection. Both schedules of reinforcement revealed a high motivation to self-administer nicotine, with monkeys continuing to press the lever when up to 600 lever-presses were needed for each injection of nicotine. Thus, nicotine, by itself, in the absence of behavioral or drug-exposure history, is a robust and highly effective reinforcer of drug-taking behavior in a non-human primate model predictive of human behavior. This supports the use of nicotinic ligands for the treatment of smokers, and this novel preclinical model offers opportunities to test future medications for the treatment of nicotine dependence.

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

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    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

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

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    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…

  15. African Non-Human Primates Host Diverse Enteroviruses

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    Mombo, Illich Manfred; Lukashev, Alexander N.; Bleicker, Tobias; Brünink, Sebastian; Berthet, Nicolas; Maganga, Gael D.; Durand, Patrick; Arnathau, Céline; Boundenga, Larson; Ngoubangoye, Barthélémy; Boué, Vanina; Liégeois, Florian; Ollomo, Benjamin; Prugnolle, Franck; Drexler, Jan Felix; Drosten, Christian; Renaud, François; Rougeron, Virginie; Leroy, Eric

    2017-01-01

    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. PMID:28081564

  16. Identification of skin immune cells in non-human primates.

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    Adam, Lucille; Rosenbaum, Pierre; Cosma, Antonio; Le Grand, Roger; Martinon, Frédéric

    2015-11-01

    The skin is a valuable target for vaccine delivery because it contains many immune cell populations, notably antigen presenting cells. Skin immune cells have been extensively described in mice and humans but not in non-human primates, which are pertinent models for immunological research in vaccination. The aim of this work was to describe immune cell populations in the epidermis, dermis and skin draining lymph nodes in cynomolgus macaques by a single 12-parameter flow cytometry protocol. Given that skin cells share several markers, we defined a gating strategy to identify accurately immune cells and to limit contamination of one immune cell population by another. The epidermis contained CD1a(+)CD1c(-) Langerhans cells (LCs), CD3(+) T cells and putative NK cells. The dermis contained CD1a(+)CD1c(-) cells, which were similar to LCs, CD1a(+)CD1c(+) dermal dendritic cells (DDCs), CD163(high)CD11b(+) resident macrophages, CD3(+) T cells and putative NK cells. The skin also contained CD66(+) polymorphonuclear cells in some animals. Thus, immune cell populations in the macaque are similar to those in humans despite some differences in phenotype. In skin draining lymph nodes, we identified migratory LCs, CD1a(+)CD1c(+) DDCs and macrophages. The simultaneous identification of these different immune cells with one panel of markers avoids the use of large amounts of precious sample and may improve the understanding of immune mechanisms in the skin after treatment or vaccination.

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

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    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

  18. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

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    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

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

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    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 pri

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

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    Van Meer, P.J.K.; Kooijman, M.; Van Der Laan, J.W.; Moors, E.H.M.; Schellekens, H.

    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 t

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

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    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…

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

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

    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), c...

  3. Trypanosomes of non-human primates from the National Centre of Primates, Ananindeua, State of Pará, Brazil

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    Ziccardi Mariangela

    2000-01-01

    Full Text Available Trypanosome infections were sought in 46 non-human primates captured principally in Amazonian Brazil. Twenty-two (47.8% were infected with four Trypanosoma species: T. cruzi, T. minasense, T. devei and T. rangeli. These preliminary results confirmed the high prevalence and diversity of natural infections with trypanosomes in primates from Brazilian Amazon and were the first formal record of simian infections with trypanosomes in the State of Acre. The presence of T. cruzi-like and T. rangeli-like parasites are recorded in four new hosts.

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

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    Chelidze, Nino

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

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

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    Merchant, Hugo; Honing, Henkjan

    2013-01-01

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

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

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    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

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

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    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.

  8. 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.

  9. Prevalence of parasitic infection in captive non human primates of Assam State Zoo, India

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    Bichitra Gopal Nath

    Full Text Available Aim: The study was conducted to know the parasitic infestation in captive non human primates of Assam State Zoo. Materials and Methods: A total of twenty two faecal samples from non human primates of different species viz. Slow loris (Nycticebus coucang (3, Pig tailed macaque (Macaca nemestrina (3, Stump-tailed macaque (Macaca arctoides (5, Assamese macaque (Macaca assamensis (1, Bonnet macaque (Macaca radiata (1, Golden langur (Trachypithecus geei (6 and Hoolock gibbon (Hylobates hoolock (3 were analysed from August, 2009 to December, 2009 by using routine sedimentation and floatation techniques as described by Georgi (1985. Identification of parasitic ova was carried out as described by Soulsby (1982 and Wallach and Boever (1983. Results: Out of 22 faecal samples examined, 1 (20% in stump-tailed macaque was found positive for Oesophagostomum spp. and 1(16.67% in golden langur and 1 (33.33% in hoolock gibbon, were found positive for the presence of Trichuris spp. Conclusion: Incidence of parasitic infection was 13.63% in captive non human primates of Assam State Zoo. [Vet World 2012; 5(10.000: 614-616

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

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    Katherine A Leighty

    Full Text Available 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.

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

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    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.

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

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    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.

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

    Science.gov (United States)

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

    2012-01-01

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

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

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    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.

  15. 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.

  16. Cloning of non-human primates: the road “less traveled by”

    Science.gov (United States)

    SPARMAN, MICHELLE L.; TACHIBANA, MASAHITO; MITALIPOV, SHOUKHRAT M.

    2011-01-01

    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. PMID:21404187

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

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    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.

  18. [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.

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

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    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.

  20. Challenges in Mucosal HIV Vaccine Development: Lessons from Non-Human Primate Models

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    Iskra Tuero

    2014-08-01

    Full Text Available An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinical studies in non-human primate models have facilitated progress in mucosal vaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosal samples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-human primate studies which have provided important information for future design of vaccine strategies, targeting of mucosal inductive sites, and assessment of mucosal immunity. Knowledge gained in these studies will inform mucosal vaccine design and evaluation in human clinical trials.

  1. 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

  2. Diffeomorphic registration with self-adaptive spatial regularization for the segmentation of non-human primate brains.

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    Risser, Laurent; Dolius, Lionel; Fonta, Caroline; Mescam, Muriel

    2014-01-01

    Cerebral aging has been linked to structural and functional changes in the brain throughout life. Here, we study the marmoset, a small non-human primate, in order to get insights into the mechanisms of brain aging in normal and pathological conditions. Imaging the brain of small animals with techniques such as MRI, quickly becomes a challenging task when compared with human brain imaging. Very often, a simple pre-processing step such as brain extraction cannot be achieved with classical tools. In this paper, we propose a diffeomorphic registration algorithm, which makes use of learned constraints to propagate the manual segmentation of a marmoset brain template to other MR images of marmoset brains. The main methological contribution of our paper is to explore a new strategy to automatically tune the spatial regularization of the deformations. Results show that we obtain a robust segmentation of the brain, even for images with a low contrast.

  3. Structural variations of the VWA locus in humans and comparison with non-human primates.

    Science.gov (United States)

    Minaguchi, K; Takenaka, O

    2000-09-11

    The HUMVWA locus was examined in 160 samples from the Japanese population. A total of 142 fragments were sequenced, and the counterpart sequences were also determined in non-human primates. In humans, 10 different alleles were found; they could be grouped into seven allelic classes based on the total number of repeats. No variation was observed in the alleles 17, 18 and 19, which showed consensus sequence structures and in the allele 14, which showed a different structure. New variation was found in alleles 15, 16, and 20, which had differences occurred in a basic (TCTA)(TCTG)(n) repeat in the 5' side. The counterpart fragments were successfully amplified in three species (chimpanzees, gorilla, and orangutan) out of four kinds of anthropoids, three species (rhesus macaques, Japanese macaques, and green monkey) out of four kinds of old world monkeys, but not in one species of either new world monkey or prosimian. The sizes of the fragments distributed from 92 to 180 bp in non-human primates and showed allelic size differences in four species. The sequence of the 5' flanking region followed by primer sequences in humans and anthropoids, which consisted of 19 bp, was identical in all, but differed from that in old world monkeys. The basic repeat motifs of humans and anthropoids consisted of TCTA, TCTG, and TCCA but that of old world monkeys consisted of TCTG, TCCG and TCCA The structures of humans and anthropoids were essentially similar, but with characteristic difference in each species. Differences in the allelic structures of old world monkeys were complex. Seven different alleles were observed in two rhesus and two Japanese macaques and one type of allele was observed in two green monkeys. Duplication of more than two repeat units of 4 bp was found in an allele of an old world monkey. These data illuminate interesting features of mutational changes in STRs during the long generations and also some insight into evolutional aspects of primates.

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

    Science.gov (United States)

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

    1986-01-01

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

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

    Science.gov (United States)

    Lefebvre, Louis

    2013-01-01

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

  6. 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.

  7. Non-human primate and rodent embryonic stem cells are differentially sensitive to embryotoxic compounds

    Directory of Open Access Journals (Sweden)

    Lauren Walker

    2015-01-01

    First, osteogenic capacity was compared between ESCs from the mouse and a New World monkey, the common marmoset. Then, cells were treated with compounds that have been previously reported to induce bone teratogenicity. Calcification and MTT assays evaluated effects on osteogenesis and cell viability, respectively. Our data indicated that marmoset ESCs responded differently than mouse ESCs in such embryotoxicity screens with no obvious dependency on chemical or compound classes and thus suggest that embryotoxicity screening results could be affected by species-driven response variation. In addition, ESCs derived from rhesus monkey, an Old World monkey, and phylogenetically closer to humans than the marmoset, were observed to respond differently to test compounds than marmoset ESCs. Together these results indicate that there are significant differences in the responses of non-human primate and mouse ESC to embryotoxic agents.

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

    Science.gov (United States)

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

    2014-01-01

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

  9. The neural bases of crossmodal object recognition in non-human primates and rodents: a review.

    Science.gov (United States)

    Cloke, Jacob M; Jacklin, Derek L; Winters, Boyer D

    2015-05-15

    The ability to integrate information from different sensory modalities to form unique multisensory object representations is a highly adaptive cognitive function. Surprisingly, non-human animal studies of the neural substrates of this form of multisensory integration have been somewhat sparse until very recently, and this may be due in part to a relative paucity of viable testing methods. Here we review the historical development and use of various "crossmodal" cognition tasks for non-human primates and rodents, focusing on tests of "crossmodal object recognition", the ability to recognize an object across sensory modalities. Such procedures have great potential to elucidate the cognitive and neural bases of object representation as it pertains to perception and memory. Indeed, these studies have revealed roles in crossmodal cognition for various brain regions (e.g., prefrontal and temporal cortices) and neurochemical systems (e.g., acetylcholine). A recent increase in behavioral and physiological studies of crossmodal cognition in rodents augurs well for the future of this research area, which should provide essential information about the basic mechanisms of object representation in the brain, in addition to fostering a better understanding of the causes of, and potential treatments for, cognitive deficits in human diseases characterized by atypical multisensory integration.

  10. 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.

  11. 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.

  12. 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.

  13. A new non-human primate model of photochemically induced cerebral infarction.

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    Satoshi Ikeda

    Full Text Available BACKGROUND AND PURPOSE: Rat models of photochemically induced cerebral infarction have been readily studied, but to date there are no reports of transcranial photochemically induced infarctions in the marmoset. In this report, we used this non-human primate as a model of cerebral thrombosis and observed the recovery process. METHODS: Five common marmosets were used. Cerebral ischemia was produced via intravascular thrombosis induced by an intravenous injection of Rose Bengal and irradiation with green light. After inducing cerebral infarction, we observed the behavior of marmosets via a continuous video recording. We evaluated maximum speed, mean speed, and distance traveled in 1 min. In addition, we evaluated scores for feeding behavior, upper limb grip, and lower limb grip. We confirmed the infarct area after cerebral infarction using 2,3,5-triphenyltetrazolium chloride staining in a separate marmoset. RESULTS: We found functional decreases 2 days after creating the cerebral infarction in all measurements. Total distance traveled, average speed, upper limb score, and feeding behavior score did not recover to pre-infarction levels within 28 days. Maximum speed in 1 min and lower limb score recovered 28 days after infarction as compared to pre-infarction levels. We confirmed the infarct area of 11.4 mm × 6.8 mm as stained with 2,3,5-triphenyltetrazolium chloride. CONCLUSION: We were able to create a primate photothrombosis-induced cerebral infarction model using marmosets and observe functional recovery. We suggest that this is a useful model for basic research of cerebral infarction.

  14. 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.

  15. 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.

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

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

    2015-01-01

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

  17. 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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    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.

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

    Science.gov (United States)

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

    2015-08-01

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

  19. On the scent of human olfactory orbitofrontal cortex: meta-analysis and comparison to non-human primates.

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    Gottfried, Jay A; Zald, David H

    2005-12-15

    It is widely accepted that the orbitofrontal cortex (OFC) represents the main neocortical target of primary olfactory cortex. In non-human primates, the olfactory neocortex is situated along the basal surface of the caudal frontal lobes, encompassing agranular and dysgranular OFC medially and agranular insula laterally, where this latter structure wraps onto the posterior orbital surface. Direct afferent inputs arrive from most primary olfactory areas, including piriform cortex, amygdala, and entorhinal cortex, in the absence of an obligatory thalamic relay. While such findings are almost exclusively derived from animal data, recent cytoarchitectonic studies indicate a close anatomical correspondence between non-human primate and human OFC. Given this cross-species conservation of structure, it has generally been presumed that the olfactory projection area in human OFC occupies the same posterior portions of OFC as seen in non-human primates. This review questions this assumption by providing a critical survey of the localization of primate and human olfactory neocortex. Based on a meta-analysis of human functional neuroimaging studies, the region of human OFC showing the greatest olfactory responsivity appears substantially rostral and in a different cytoarchitectural area than the orbital olfactory regions as defined in the monkey. While this anatomical discrepancy may principally arise from methodological differences across species, these results have implications for the interpretation of prior human lesion and neuroimaging studies and suggest constraints upon functional extrapolations from animal data.

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

    Science.gov (United States)

    Zhang, Bo

    2017-01-01

    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. PMID:28271667

  1. 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.

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

    Science.gov (United States)

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

    2015-01-29

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

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

    Science.gov (United States)

    Bailey, Jarrod; Taylor, Kathy

    2016-03-01

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

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

    Science.gov (United States)

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

    2012-11-15

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

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

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    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.

  6. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration.

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    Freeman, Willard M; Vanguilder, Heather D; Guidone, Elizabeth; Krystal, John H; Grant, Kathleen A; Vrana, Kent E

    2011-08-01

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. Two-dimensional difference in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within-subject samples collected before exposure to ethanol and after 3 months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of serum amyloid A4 (SAA4), retinol-binding protein, inter-alpha inhibitor H4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption.

  7. Manganese exposure induces α-synuclein aggregation in the frontal cortex of non-human primates.

    Science.gov (United States)

    Verina, Tatyana; Schneider, Jay S; Guilarte, Tomás R

    2013-03-13

    Aggregation of α-synuclein (α-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is associated with a neurological syndrome consisting of psychiatric symptoms, cognitive impairment and parkinsonism. In this study, we examined α-syn immunoreactivity in the frontal cortex of Cynomolgus macaques as part of a multidisciplinary assessment of the neurological effects produced by exposure to moderate levels of Mn. We found increased α-syn-positive cells in the gray matter of Mn-exposed animals, typically observed in pyramidal and medium-sized neurons in deep cortical layers. Some of these neurons displayed loss of Nissl staining with α-syn-positive spherical aggregates. In the white matter we also observed α-syn-positive glial cells and in some cases α-syn-positive neurites. These findings suggest that Mn exposure promotes α-syn aggregation in neuronal and glial cells that may ultimately lead to degeneration in the frontal cortex gray and white matter. To our knowledge, this is the first report of Mn-induced neuronal and glial cell α-syn accumulation and aggregation in the frontal cortex of non-human primates.

  8. 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.

  9. Hominin geographical range dynamics and relative brain size: Do non-human primates provide a good analogy?

    Science.gov (United States)

    MacDonald, Katharine; Smaers, Jeroen B; Steele, James

    2015-10-01

    We use climatic and satellite remote sensing data to characterize environmental seasonality in the geographical ranges of extant non-human primates in order to assess the effect of relative brain size on tolerance of more seasonal habitats. Demonstration of such an effect in living non-human primates could provide a comparative framework for modeling hominin dispersals and geographical range dynamics in the Pliocene and Pleistocene. Our analyses found no such effect: there are neither positive nor negative correlations between relative brain size and either geographical range size or the average and range of values for environmental seasonality, whether analysed at the level of all primates, or within parvorders (strepsirrhine, catarrhine, platyrrhine). Independent analyses by other researchers comparing feeding behaviour and ecology at individual primate study sites demonstrate that in seasonal environments, the year-round metabolic costs of maintaining a relatively large brain are met by adaptive behavioural/dietary strategies. However, consistent with our own results, those comparative studies found that there was no overall association, whether positive or negative, between 'raw' environmental seasonality and primate relative brain size. We must therefore look elsewhere for a comparative model of hominin geographical range dynamics in the Pleistocene.

  10. Animal Welfares of Laboratory Non-Human Primates%非人灵长类动物实验中的动物福利

    Institute of Scientific and Technical Information of China (English)

    陈乾生

    2003-01-01

    While comparing non-human primates with human beings, it is not hard to conclude certain similarities between these two based on aspects such as morphological anatomy, biochemistry functioning and so on. As a result, nonhuman primates often play an important role in life scientific researches. These primates are always used as "Stand-Ins"for human beings. In the processes of toxicological testing of new drugs, some drugs, especially drugs of genic projects or biological medicines are requiring uses of primates as part of the new drug testing. Therefore, the morality and ethics of using non-human primates have to be emphasised by people. After all, this is one of the issues that concerns with the expectations of meeting the international scientific research standards by our national laboratory animal sciences.In fact, the moral and ethical problems of non-human primates experiments is related to the matters of animal welfares.

  11. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. Grooming-at-a-distance by exchanging calls in non-human primates.

    Science.gov (United States)

    Arlet, Malgorzata; Jubin, Ronan; Masataka, Nobuo; Lemasson, Alban

    2015-10-01

    The 'social bonding hypothesis' predicts that, in large social groups, functions of gestural grooming should be partially transferred to vocal interactions. Hence, vocal exchanges would have evolved in primates to play the role of grooming-at-a-distance in order to facilitate the maintenance of social cohesion. However, there are few empirical studies testing this hypothesis. To address this point, we compared the rate of contact call exchanges between females in two captive groups of Japanese macaques as a function of female age, dominance rank, genetic relatedness and social affinity measured by spatial proximity and grooming interactions. We found a significant positive relationship between the time spent on grooming by two females and the frequency with which they exchanged calls. Our results conform to the predictions of the social bonding hypothesis, i.e. vocal exchanges can be interpreted as grooming-at-a-distance.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    NARCIS (Netherlands)

    Datson, N.A.; Morsink, M.C.; Atanasova, S.; Armstrong, V.W.; Zischler, H.; Schlumbohm, C.; Dutilh, B.E.; Huynen, M.A.; Waegele, B.; Ruepp, A.; Kloet, E.R. de; Fuchs, E.

    2007-01-01

    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 marmo

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Yaping Wang

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Using naturalistic utterances to investigate vocal communication processing and development in human and non-human primates.

    Science.gov (United States)

    Talkington, William J; Taglialatela, Jared P; Lewis, James W

    2013-11-01

    Humans and several non-human primates possess cortical regions that are most sensitive to vocalizations produced by their own kind (conspecifics). However, the use of speech and other broadly defined categories of behaviorally relevant natural sounds has led to many discrepancies regarding where voice-sensitivity occurs, and more generally the identification of cortical networks, "proto-networks" or protolanguage networks, and pathways that may be sensitive or selective for certain aspects of vocalization processing. In this prospective review we examine different approaches for exploring vocal communication processing, including pathways that may be, or become, specialized for conspecific utterances. In particular, we address the use of naturally produced non-stereotypical vocalizations (mimicry of other animal calls) as another category of vocalization for use with human and non-human primate auditory systems. We focus this review on two main themes, including progress and future ideas for studying vocalization processing in great apes (chimpanzees) and in very early stages of human development, including infants and fetuses. Advancing our understanding of the fundamental principles that govern the evolution and early development of cortical pathways for processing non-verbal communication utterances is expected to lead to better diagnoses and early intervention strategies in children with communication disorders, improve rehabilitation of communication disorders resulting from brain injury, and develop new strategies for intelligent hearing aid and implant design that can better enhance speech signals in noisy environments. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".

  4. 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

    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. PMID:28125696

  5. Reported analgesic administration to rabbits, pigs, sheep, dogs and non-human primates undergoing experimental surgical procedures.

    Science.gov (United States)

    Coulter, C A; Flecknell, P A; Richardson, C A

    2009-07-01

    Reported analgesic use following experimental surgery is low in rodents and there has been little published information on the frequency of analgesic use in other laboratory species. A structured literature review was conducted to examine analgesic administration in larger laboratory animals. The Scirus search engine was used to identify studies published in peer-reviewed journals that reported carrying out experimental surgery on 'large' laboratory animals, specifically rabbits, pigs, sheep, dogs and non-human primates. Seventy-four studies between 2000 and 2001 and 75 studies between 2005 and 2006 were included in the review. There was an increase in the reported administration of systemic analgesics to these species from 50% in 2000-2001 to 63% in 2005-2006. When all agents with analgesic properties were considered (systemic analgesics, local anaesthetics and anaesthetics with analgesic components), the proportion of papers that reported some form of analgesic administration to 'large' laboratory animals increased from 86% in 2000-2001 to 89% in 2005-2006. Overall rabbits, pigs, sheep, dogs and non-human primates were more likely to receive analgesics following potentially painful experimental procedures than has been reported in laboratory rodents but analgesic administration to 'large' laboratory species is still not optimal.

  6. Primate Innovation: Sex, Age and Social Rank

    NARCIS (Netherlands)

    Reader, S.M.; Laland, K.N.

    2001-01-01

    Analysis of an exhaustive survey of primate behavior collated from the published literature revealed significant variation in rates of innovation among individuals of different sex, age and social rank. We searched approximately 1,000 articles in four primatology journals, together with other releva

  7. 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.

  8. 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.

  9. Long-Term Two-Photon Calcium Imaging of Neuronal Populations with Subcellular Resolution in Adult Non-human Primates.

    Science.gov (United States)

    Sadakane, Osamu; Masamizu, Yoshito; Watakabe, Akiya; Terada, Shin-Ichiro; Ohtsuka, Masanari; Takaji, Masafumi; Mizukami, Hiroaki; Ozawa, Keiya; Kawasaki, Hiroshi; Matsuzaki, Masanori; Yamamori, Tetsuo

    2015-12-01

    Two-photon imaging with genetically encoded calcium indicators (GECIs) enables long-term observation of neuronal activity in vivo. However, there are very few studies of GECIs in primates. Here, we report a method for long-term imaging of a GECI, GCaMP6f, expressed from adeno-associated virus vectors in cortical neurons of the adult common marmoset (Callithrix jacchus), a small New World primate. We used a tetracycline-inducible expression system to robustly amplify neuronal GCaMP6f expression and up- and downregulate it for more than 100 days. We succeeded in monitoring spontaneous activity not only from hundreds of neurons three-dimensionally distributed in layers 2 and 3 but also from single dendrites and axons in layer 1. Furthermore, we detected selective activities from somata, dendrites, and axons in the somatosensory cortex responding to specific tactile stimuli. Our results provide a way to investigate the organization and plasticity of cortical microcircuits at subcellular resolution in non-human primates.

  10. 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.

  11. Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.

    Science.gov (United States)

    Wang, Junru; Shao, Lijian; Hendrickson, Howard P; Liu, Liya; Chang, Jianhui; Luo, Yi; Seng, John; Pouliot, Mylene; Authier, Simon; Zhou, Daohong; Allaben, William; Hauer-Jensen, Martin

    2015-11-01

    The non-human primate has been a useful model for studies of human acute radiation syndrome (ARS). However, to date structural changes in various parts of the intestine after total body irradiation (TBI) have not been systematically studied in this model. Here we report on our current study of TBI-induced intestinal structural injury in the non-human primate after doses typically associated with hematopoietic ARS. Twenty-four non-human primates were divided into three groups: sham-irradiated control group; and total body cobalt-60 (60Co) 6.7 Gy gamma-irradiated group; and total body 60Co 7.4 Gy gamma-irradiated group. After animals were euthanized at day 4, 7 and 12 postirradiation, sections of small intestine (duodenum, proximal jejunum, distal jejunum and ileum) were collected and fixed in 10% formalin. The intestinal mucosal surface length, villus height and crypt depths were assessed by computer-assisted image analysis. Plasma citrulline levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total bone marrow cells were counted and hematopoietic stem/progenitor cells in bone marrow were analyzed by flow cytometer. Histopathologically, all segments exhibited conspicuous disappearance of plicae circulares and prominent atrophy of crypts and villi. Intestinal mucosal surface length was significantly decreased in all intestinal segments on day 4, 7 and 12 after irradiation (P 0.05). Crypt depth was also significantly reduced in all segments on day 4, 7 and 12 after irradiation (P irradiation, consistent with intestinal mucosal injury. Both 6.7 and 7.4 Gy TBI reduced total number of bone marrow cells. And further analysis showed that the number and function of CD45(+)CD34(+) hematopoietic stem/progenitors in bone marrow decreased significantly. In summary, TBI in the hematopoietic ARS dose range induces substantial intestinal injury in all segments of the small bowel. These findings underscore the importance of maintaining the

  12. 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...... received increasing doses of belinostat (10-60 mg/kg) as a 30-min IV infusion. Serial blood and CSF samples were collected over 48 h. Plasma and CSF concentrations of belinostat were quantified with an LC/MS/MS assay. Pharmacokinetic parameters were calculated using non-compartmental methods, and CSF....... CSF drug exposure was drug exposure and drug exposure. CONCLUSION: IV belinostat is rapidly cleared from plasma and has limited penetration into the CSF Udgivelsesdato: 2008/8...

  13. Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates.

    Science.gov (United States)

    Lukashevich, Igor S; Carrion, Ricardo; Salvato, Maria S; Mansfield, Keith; Brasky, Kathleen; Zapata, Juan; Cairo, Cristiana; Goicochea, Marco; Hoosien, Gia E; Ticer, Anysha; Bryant, Joseph; Davis, Harry; Hammamieh, Rasha; Mayda, Maria; Jett, Marti; Patterson, Jean

    2008-09-26

    A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever.

  14. 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.

  15. 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...... 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...

  16. The rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model.

    Science.gov (United States)

    Jie, Zhijun; Sun, Wei; Wang, Shanze; Koster, Frederick; Li, Bilan; Harrod, Kevin S

    2014-01-01

    Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

  17. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

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    Vadim I Krivokrysenko

    Full Text Available There are currently no approved medical radiation countermeasures (MRC to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01 absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05 effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.

  18. Appetite enhancement and weight gain by peripheral administration of TrkB agonists in non-human primates.

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    John C Lin

    Full Text Available Loss of function mutations in the receptor tyrosine kinase TrkB pathway resulted in hyperphagia and morbid obesity in human and rodents. Conversely, peripheral or central stimulation of TrkB by its natural ligands BDNF or NT4 reduced body weight and food intake in mice, supporting the idea that TrkB is a key anorexigenic signal downstream of the melanocortin-4 receptor (Mc4r system. Here we show that in non-human primates TrkB agonists were anorexigenic when applied centrally, but surprisingly orexigenic, leading to gain in appetite, body weight, fat deposits and serum leptin levels, when given peripherally. The orexigenic and pro-obesity effects of peripherally administered TrkB agonists appear to be dose dependent, not associated with fluid retention nor with evidence of receptor down regulation. Our findings revealed that TrkB signaling exerts dual control on energy homeostasis in the primates that could be targeted for the treatment of either wasting disorders or obesity.

  19. Reference in human and non-human primate communication: What does it take to refer?

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    Sievers, Christine; Gruber, Thibaud

    2016-07-01

    The concept of functional reference has been used to isolate potentially referential vocal signals in animal communication. However, its relatedness to the phenomenon of reference in human language has recently been brought into question. While some researchers have suggested abandoning the concept of functional reference altogether, others advocate a revision of its definition to include contextual cues that play a role in signal production and perception. Empirical and theoretical work on functional reference has also put much emphasis on how the receiver understands the referential signal. However, reference, as defined in the linguistic literature, is an action of the producer, and therefore, any definition describing reference in non-human animals must also focus on the producer. To successfully determine whether a signal is used to refer, we suggest an approach from the field of pragmatics, taking a closer look at specific situations of signal production, specifically at the factors that influence the production of a signal by an individual. We define the concept of signaller's reference to identify intentional acts of reference produced by a signaller independently of the communicative modality, and illustrate it with a case study of the hoo vocalizations produced by wild chimpanzees during travel. This novel framework introduces an intentional approach to referentiality. It may therefore permit a closer comparison of human and non-human animal referential behaviour and underlying cognitive processes, allowing us to identify what may have emerged solely in the human lineage.

  20. Molecular identification and characterization of Mycobacterium avium subspecies paratuberculosis in free living non-human primate (Rhesus macaques) from North India.

    Science.gov (United States)

    Singh, S V; Singh, A V; Singh, P K; Kumar, A; Singh, B

    2011-05-01

    In recent years, Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as major animal pathogen with significant zoonotic concerns, worldwide. MAP infection is endemic in domestic and wild ruminant population in India. However, information on MAP infection in free ranging animal species and non human primates is limited. Present study aimed to estimate the status of MAP infection in free living Rhesus macaques suffering with multiple clinical conditions (coughing and loose stool). A total of 25 stool samples were collected from six colonies of Rhesus macaques from Mathura region (North India) and screened for the presence of MAP, using microscopic examination and IS900 PCR, directly from stool samples. PCR positive DNA samples were further genotyped using IS1311 PCR-restriction enzyme analysis. Of the 25 stool samples, 10 (40.0%) and 2 (8.0%) were positive for MAP using microscopic examination and direct IS900 PCR, respectively. IS900 PCR positive DNA samples were genotyped as 'Indian Bison type', which is a major MAP genotype infecting domestic and wild ruminant species and human beings in India. Prevalence of MAP in Rhesus macaques (Indian monkeys) was moderately high and confirmed interspecies sharing of MAP between domestic livestock and non-human primates. Presence of MAP in non-human primates, support the etiological role of MAP in inflammatory bowel disease patients. Indian monkeys may serve as model for understanding the role of non-human primates in sustenance, transmission and pathogenesis of MAP infection.

  1. 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.

  2. Temporal and spatial categorization in human and non-human primates.

    Science.gov (United States)

    Mendez, Juan Carlos; Prado, Luis; Mendoza, German; Merchant, Hugo

    2011-01-01

    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 toward common or at least partially overlapped neural circuits for temporal and spatial categorization in primates.

  3. 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.

  4. 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.

  5. An implicit measure of olfactory performance for non-human primates reveals aversive and pleasant odor conditioning.

    Science.gov (United States)

    Livneh, Uri; Paz, Rony

    2010-09-30

    We have little understanding of how odorants are processed in neural networks of the primate brain. Because chemo-stimuli are harder to control than physical stimuli (e.g. vision, audition), such research was limited by the temporal resolution, accuracy, and reliability of olfactometers (odor producing machines). Recent advances were able to create olfactometers that overcome these limitations, allowing their use together with neuroimaging techniques in humans. From the behavioral point of view, olfaction research requires a behavioral measure that can be used to quantify olfactory performance. This becomes a real problem when working with animals, where, unlike humans, explicit measures are harder to obtain. Furthermore, because odorants are powerful primitive reinforcers, such implicit measures can be beneficial to use in learning paradigms. Here we describe an olfactometer suitable for use in non-human primates, and an end-port design that allows the accurate measure of real-time respiratory modulations that are elicited in response to odor presentation. We demonstrate that this implicit measure is differentially modulated when experiencing pleasant or aversive odors. We then present an experimental paradigm in which monkeys learn to associate tones with odors, and show that the time delay from the conditioned stimuli to the next breath can be used to measure learning and memory expression in this paradigm. Using this construct, we reveal olfactory performance during acquisition and extinction of odor conditioning. These techniques can be used in electrophysiological recordings from relevant brain areas to shed light on neural networks involved in odor processing and reinforcement-learning.

  6. 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

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

    Science.gov (United States)

    2011-01-01

    investigate alterations in the retinal proteome as a result of diabetes, age-related macular degeneration , or glaucoma. Some studies have assessed the...13. Hollyfield JG, Salomon RG, Crabb JW. Proteomic approaches to understanding age-related macular degeneration . Adv Exp Med Biol 2003; 533:83-9...using the C18 reverse phase column (1 µl/min flow rate) in line with the mass spectrometer. Mobile phases consisted of 0.1% formic acid, 5

  8. Could an experimental dengue virus infection fail to induce solid immunity against homologous viral challenge in non-human primates?

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Lazo, Laura; Marcos, Ernesto; Martín, Jorge; Suzarte, Edith; Castro, Jorge; Romero, Yaremis; Guillén, Gerardo; Hermida, Lisset

    2016-02-01

    There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate. Some authors have tried to explain this contradiction by hypothesizing that protection rates in non-human primates (NHPs) are associated with a lack of post-challenge anamnestic immune responses. Here, we studied the protection and anamnestic response patterns after homologous challenge in NHPs previously infected with DENV-2. Two immunization schemes were used, varying the viral doses and the intervals between them. Animals developed immunity against DENV-2 that provided full protection against reinfection with a homologous virus. However, all monkeys showed a significant increase in antiviral and neutralizing antibody titers after challenge. Our results suggest that sterilizing immunity could not be induced by infection with the virus despite the lack of detectable viremia in some animals in which an increase in antibody titer was observed. For this reason, we propose that the lack of an anamnestic neutralizing antibody response after challenge, as suggested by some authors, should be carefully reviewed as a criterion for evaluating the functionality of vaccine candidates.

  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. GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells.

    Science.gov (United States)

    D'Souza, Saritha S; Maufort, John; Kumar, Akhilesh; Zhang, Jiuchun; Smuga-Otto, Kimberley; Thomson, James A; Slukvin, Igor I

    2016-02-09

    Advances in the scalable production of blood cells from induced pluripotent stem cells (iPSCs) open prospects for the clinical translation of de novo generated blood products, and evoke the need for preclinical evaluation of their efficacy, safety, and immunogenicity in large animal models. Due to substantial similarities with humans, the outcomes of cellular therapies in non-human primate (NHP) models can be readily extrapolated to a clinical setting. However, the use of this model is hampered by relatively low efficiency of blood generation and lack of lymphoid potential in NHP-iPSC differentiation cultures. Here, we generated transgene-free iPSCs from different NHP species and showed the efficient induction of mesoderm, myeloid, and lymphoid cells from these iPSCs using a GSK3β inhibitor. Overall, our studies enable scalable production of hematopoietic progenitors from NHP-iPSCs, and lay the foundation for preclinical testing of iPSC-based therapies for blood and immune system diseases in an NHP model.

  11. GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells

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    Saritha S. D'Souza

    2016-02-01

    Full Text Available Advances in the scalable production of blood cells from induced pluripotent stem cells (iPSCs open prospects for the clinical translation of de novo generated blood products, and evoke the need for preclinical evaluation of their efficacy, safety, and immunogenicity in large animal models. Due to substantial similarities with humans, the outcomes of cellular therapies in non-human primate (NHP models can be readily extrapolated to a clinical setting. However, the use of this model is hampered by relatively low efficiency of blood generation and lack of lymphoid potential in NHP-iPSC differentiation cultures. Here, we generated transgene-free iPSCs from different NHP species and showed the efficient induction of mesoderm, myeloid, and lymphoid cells from these iPSCs using a GSK3β inhibitor. Overall, our studies enable scalable production of hematopoietic progenitors from NHP-iPSCs, and lay the foundation for preclinical testing of iPSC-based therapies for blood and immune system diseases in an NHP model.

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

    Institute of Scientific and Technical Information of China (English)

    Madhusudana Girija Sanal

    2011-01-01

    Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and im-plantable bioengineered constructs. Reproducing the complex relations between different cell types, gen-eration of adequate vasculature, and immunological complications are road blocks in generation of bioengi-neered 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 lack-ing 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 ap-proach can be curative in genetic disorders as this of-fers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tet-raploid 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 sig-naling 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.

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

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    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.

  14. 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.

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

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    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

  16. Detection of antibodies to Oropouche virus in non-human primates in Goiânia City, Goiás

    OpenAIRE

    2016-01-01

    Abstract: INTRODUCTION Arboviruses are associated with human disease, and non-human primates (NHPs) are important primary hosts. This study shows the detection of antibodies to Oropouche virus (OROV) in NHPs either living in urban parks or acclimatized at the Wild Animal Screening Center, Goiânia city. METHODS: Fifty blood samples were analyzed by hemagglutination-inhibition and neutralization assays. RESULTS: Two monkeys (Alouatta caraya) had antibodies to OROV by both techniques. CONCL...

  17. On the pursuit of the brain network for proto-syntactic learning in non-human primates: conceptual issues and neurobiological hypotheses.

    Science.gov (United States)

    Petkov, Christopher I; Wilson, Benjamin

    2012-07-19

    Songbirds have become impressive neurobiological models for aspects of human verbal communication because they learn to sequence their song elements, analogous, in some ways, to how humans learn to produce spoken sequences with syntactic structure. However, mammals such as non-human primates are considered to be at best limited-vocal learners and not able to sequence their vocalizations, although some of these animals can learn certain 'artificial grammar' sequences. Thus, conceptual issues have slowed the progress in exploring potential neurobiological homologues to language-related processes in species that are taxonomically closely related to humans. We consider some of the conceptual issues impeding a pursuit of, as we define them, 'proto-syntactic' capabilities and their neuronal substrates in non-human animals. We also discuss ways to better bridge comparative behavioural and neurobiological data between humans and other animals. Finally, we propose guiding neurobiological hypotheses with which we aim to facilitate the future testing of the level of correspondence between the human brain network for syntactic-learning and related neurobiological networks present in other primates. Insights from the study of non-human primates and other mammals are likely to complement those being obtained in birds to further our knowledge of the human language-related network at the cellular level.

  18. Real-time, transcranial monitoring of safe blood-brain barrier opening in non-human primates.

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    Fabrice Marquet

    Full Text Available The delivery of drugs to specific neural targets faces two fundamental problems: (1 most drugs do not cross the blood-brain barrier, and (2 those that do, spread to the entire brain. To date, there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier (BBB opening using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500-kHz spherical transducer ultrasound setup for targeted BBB opening in the non-human primate that does not require simultaneous MRI monitoring. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. In this paper, the accuracy of this system was tested by targeting caudate nucleus and putamen of the basal ganglia in two macaque monkeys. The average lateral targeting error of the system was ∼2.5 mm while the axial targeting error, i.e., along the ultrasound path, was ∼1.5 mm. We have also developed a real-time treatment monitoring technique based on cavitation spectral analysis. This technique also allowed for delineation of a safe and reliable acoustic parameter window for BBB opening. In summary, the targeting accuracy of the system was deemed to be suitable to reliably open the BBB in specific sub-structures of the basal ganglia even in the absence of MRI-based verification of opening volume and position. This establishes the method and the system as a potentially highly useful tool for brain drug delivery.

  19. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species

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    Armstrong Dianna

    2004-12-01

    Full Text Available Abstract Background The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. Methods Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans, yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. Results In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. Conclusions The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example may relate either directly or indirectly to a lymphatic CSF absorption deficit.

  20. B-Cells and the Use of Non-Human Primates for Evaluation of HIV Vaccine Candidates.

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    Demberg, Thorsten; Robert-Guroff, Marjorie

    2015-01-01

    The RV144 clinical trial in Thailand associated vaccine-induced antibodies with protective efficacy, leading to a focus in HIV vaccine research on protective antibody induction. This has necessitated greater understanding of B cell biology in humans as well as non-human primates (NHP), the principle animal model for pre-clinical HIV/SIV vaccine research. This review covers development and maturation of NHP B cells within the framework of current knowledge of human and murine B cells. Identification of many NHP B cell subpopulations is now possible, although consensus is lacking in some cases, and better distinction of some populations is still needed. Elucidation of mechanisms that control germinal center maintenance, selection of B cells into the memory cell pool, and differentiation of B cells into long-lived plasma cells remains critical for improving vaccine design. B cell dysfunction occurs during both HIV and SIV infection. Whether the processes leading to this impairment are identical in humans and NHP is not known. Uncovering the mechanisms involved could lead to improved treatment regimens. The SIV/NHP model effectively mimics HIV infection of people, but key differences between NHP and humans in antibody characteristics such as glycosylation and structure may lead to unexpected outcomes in pre-clinical studies. Important new areas for investigation include the role of B cell cytokines in the immune system and the impact of the microbiome on B cell development and maturation. Enhanced knowledge of B cells in NHP as well as humans should enable improved vaccine design, leading to induction of potent, long-lasting protective antibodies.

  1. Mechanical Design and Analysis of a Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates.

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    Sparrey, Carolyn J; Salegio, Ernesto A; Camisa, William; Tam, Horace; Beattie, Michael S; Bresnahan, Jacqueline C

    2016-06-15

    Non-human primate (NHP) models of spinal cord injury better reflect human injury and provide a better foundation to evaluate potential treatments and functional outcomes. We combined finite element (FE) and surrogate models with impact data derived from in vivo experiments to define the impact mechanics needed to generate a moderate severity unilateral cervical contusion injury in NHPs (Macaca mulatta). Three independent variables (impactor displacement, alignment, and pre-load) were examined to determine their effects on tissue level stresses and strains. Mechanical measures of peak force, peak displacement, peak energy, and tissue stiffness were analyzed as potential determinants of injury severity. Data generated from FE simulations predicted a lateral shift of the spinal cord at high levels of compression (>64%) during impact. Submillimeter changes in mediolateral impactor position over the midline increased peak impact forces (>50%). Surrogate cords established a 0.5 N pre-load protocol for positioning the impactor tip onto the dural surface to define a consistent dorsoventral baseline position before impact, which corresponded with cerebrospinal fluid displacement and entrapment of the spinal cord against the vertebral canal. Based on our simulations, impactor alignment and pre-load were strong contributors to the variable mechanical and functional outcomes observed in in vivo experiments. Peak displacement of 4 mm after a 0.5N pre-load aligned 0.5-1.0 mm over the midline should result in a moderate severity injury; however, the observed peak force and calculated peak energy and tissue stiffness are required to properly characterize the severity and variability of in vivo NHP contusion injuries.

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

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    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.

  3. An analysis approach for high-field fMRI data from awake non-human primates.

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    Steffen Stoewer

    Full Text Available fMRI experiments with awake non-human primates (NHP have seen a surge of applications in recent years. However, the standard fMRI analysis tools designed for human experiments are not optimal for analysis of NHP fMRI data collected at high fields. There are several reasons for this, including the trial-based nature of NHP experiments, with inter-trial periods being of no interest, and segmentation artefacts and distortions that may result from field changes due to movement. We demonstrate an approach that allows us to address some of these issues consisting of the following steps: 1 Trial-based experimental design. 2 Careful control of subject movement. 3 Computer-assisted selection of trials devoid of artefacts and animal motion. 4 Nonrigid between-trial and rigid within-trial realignment of concatenated data from temporally separated trials and sessions. 5 Linear interpolation of inter-trial intervals and high-pass filtering of temporally continuous data 6 Removal of interpolated data and reconcatenation of datasets before statistical analysis with SPM. We have implemented a software toolbox, fMRI Sandbox (http://code.google.com/p/fmri-sandbox/, for semi-automated application of these processing steps that interfaces with SPM software. Here, we demonstrate that our methodology provides significant improvements for the analysis of awake monkey fMRI data acquired at high-field. The method may also be useful for clinical applications with subjects that are unwilling or unable to remain motionless for the whole duration of a functional scan.

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

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    Marie Cibot

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

  5. Differences in type I interferon signaling antagonism by dengue viruses in human and non-human primate cell lines.

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    Freddy A Medina

    2015-03-01

    Full Text Available BACKGROUND/OBJECTIVES: In vitro studies have shown that dengue virus (DENV can thwart the actions of interferon (IFN-α/β and prevent the development of an antiviral state in infected cells. Clinical studies looking at gene expression in patients with severe dengue show a reduced expression of interferon stimulated genes compared to patients with dengue fever. Interestingly, there are conflicting reports as to the ability of DENV or other flaviviruses to inhibit IFN-α/β signaling. METHODOLOGY/PRINCIPAL FINDINGS: In order to determine the relative inhibition of IFN-α/β signaling by DENVs, a method combining flow cytometry and a four-parameter logistic regression model was established. A representative isolate from DENV-1, -3 and -4 and seventeen representative isolates encompassing all DENV-2 genotypes were evaluated. All of the DENVs evaluated in this study were capable of inhibiting IFN-α/β signaling. Most of the strains were able to inhibit IFN-α/β to a degree similar to DENV strain 16681; however, DENV-2 sylvatic strains demonstrated an increased inhibition of phosphorylated signal transducer and activator of transcription (pSTAT1. Surprisingly, we were unable to observe inhibition of pSTAT1 by DENV-2 sylvatic strains or the Asian strain 16681 in non-human primate (NHP cell lines. Analysis in primary Rhesus macaque dendritic cells suggests that DENVs are capable of inhibiting IFN signaling in these cells. However, contrary to human dendritic cells, production of IFN-α was detected in the supernatant of DENV-infected Rhesus macaque dendritic cells. CONCLUSIONS: The ability of DENVs to inhibit IFN-α/β signaling is conserved. Although some variation in the inhibition was observed, the moderate differences may be difficult to correlate with clinical outcomes. DENVs were unable to inhibit pSTAT1 in NHP cell lines, but their ability to inhibit pSTAT1 in primary Rhesus macaque dendritic cells suggests that this may be a cell specific

  6. Learning at a distance II. Statistical learning of non-adjacent dependencies in a non-human primate.

    Science.gov (United States)

    Newport, Elissa L; Hauser, Marc D; Spaepen, Geertrui; Aslin, Richard N

    2004-09-01

    among learners in the types of patterned regularities they can acquire. Such studies with tamarins open interesting questions about the perceptual and computational capacities of human learners that may be essential for language acquisition, and how they may differ from those of non-human primates.

  7. Demand for nonhuman primate resources in the age of biodefense.

    Science.gov (United States)

    Patterson, Jean L; Carrion, Richardo

    2005-01-01

    The demand for nonhuman primates will undoubtedly increase to meet biomedical needs in this current age of biodefense. The availability of funding has increased the research on select agents and has created a requirement to validate results in relevant primate models. This review provides a description of current and potential biological threats that are likely to require nonhuman primates for the development of vaccines and therapeutics. Primates have been an invaluable resource in the dissection of viral disease pathogenesis as well as in testing vaccine efficacy. DNA vaccine approaches have been studied successfully for Ebola, Lassa, and anthrax in nonhuman primate models. Nonhuman primate research with monkeypox has provided insight into the role of cytokines in limiting disease severity. Biodefense research that has focused on select agents of bacterial origin has also benefited from nonhuman primate studies. Rhesus macaques have traditionally been the model of choice for anthrax research and have yielded successful findings in vaccine development. In plague research, African green monkeys have contributed to vaccine development. However, the disadvantages of current vaccines will undoubtedly require the generation of new vaccines, thus increasing the need for nonhuman primate research. Unfortunately, the current biosafety level (BSL)-3 and BSL-4 facilities equipped to perform this research are limited, which may ultimately impede progress in this era of biodefense.

  8. Comparative analysis of protocadherin-11 X-linked expression among postnatal rodents, non-human primates, and songbirds suggests its possible involvement in brain evolution.

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    Eiji Matsunaga

    Full Text Available BACKGROUND: Protocadherin-11 is a cell adhesion molecule of the cadherin superfamily. Since, only in humans, its paralog is found on the Y chromosome, it is expected that protocadherin-11X/Y plays some role in human brain evolution or sex differences. Recently, a genetic mutation of protocadherin-11X/Y was reported to be associated with a language development disorder. Here, we compared the expression of protocadherin-11 X-linked in developing postnatal brains of mouse (rodent and common marmoset (non-human primate to explore its possible involvement in mammalian brain evolution. We also investigated its expression in the Bengalese finch (songbird to explore a possible function in animal vocalization and human language faculties. METHODOLOGY/PRINCIPAL FINDINGS: Protocadherin-11 X-linked was strongly expressed in the cerebral cortex, hippocampus, amygdala and brainstem. Comparative analysis between mice and marmosets revealed that in certain areas of marmoset brain, the expression was clearly enriched. In Bengalese finches, protocadherin-11 X-linked was expressed not only in nuclei of regions of the vocal production pathway and the tracheosyringeal hypoglossal nucleus, but also in areas homologous to the mammalian amygdala and hippocampus. In both marmosets and Bengalese finches, its expression in pallial vocal control areas was developmentally regulated, and no clear expression was seen in the dorsal striatum, indicating a similarity between songbirds and non-human primates. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the enriched expression of protocadherin-11 X-linked is involved in primate brain evolution and that some similarity exists between songbirds and primates regarding the neural basis for vocalization.

  9. Evaluation of arboviruses of public health interest in free-living non-human primates (Alouatta spp., Callithrix spp., Sapajus spp.) in Brazil

    OpenAIRE

    2015-01-01

    INTRODUCTION: The aim of the present study was to evaluate the presence of arboviruses from the Flavivirus genus in asymptomatic free-living non-human primates (NHPs) living in close contact with humans and vectors in the States of Paraná and Mato Grosso do Sul, Brazil. METHODS: NHP sera samples (total n = 80, Alouatta spp. n = 07, Callithrix spp. n = 29 and Sapajus spp. n = 44) were screened for the presence of viral genomes using reverse transcription polymerase chain reaction and 10% ...

  10. [Caloric restriction in primates: how efficient as an anti-aging approach?].

    Science.gov (United States)

    Marchal, Julia; Perret, Martine; Aujard, Fabienne

    2012-12-01

    Caloric restriction (CR) is the only non-genetic intervention known to date to slow the onset of age-related diseases and increase average and maximum lifespan in several species. Its interest is continually growing, particularly for the identification of mechanisms involved in increasing longevity. Unlike studies in invertebrate and rodent models have provided some indication about the mechanisms of the CR, the efficacy of CR as an anti-aging protocol in primates has not yet been fully established. In this review we present the advantages of using non human primates as relevant models to the study of human aging in general and specifically in the context of therapeutic interventions applicable to humans, such as CR. Through the longitudinal findings in the Grey Mouse Lemur (Microcebus murinus), we stress the importance of primate studies in the context of research on aging and their potential to advance the development of molecules which can mimic the beneficial effects of CR, already observed in some species, without imposing a reduced calorie diet.

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

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    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.

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

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    Hugo eMerchant

    2014-01-01

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

  13. Establishing 'quality of life' parameters using behavioural guidelines for humane euthanasia of captive non-human primates.

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    Lambeth, Sp; Schapiro, Sj; Bernacky, Bj; Wilkerson, Gk

    2013-09-01

    Chronic pain and distress are universally accepted conditions that may adversely affect an animal's quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in the USA, a veterinarian, who has physically examined the animal and reviewed the clinical records, ultimately decides when an animal has reached a humane endpoint. To aid in the difficult process of interpreting pain and distress, we have developed specific behavioural guidelines, in addition to standard clinical information, to help define unique characteristics and traits of primates to assess and promote discussion of an individual primate's QOL, and thereby, to assist in the decision-making process regarding euthanasia. These guidelines advocate the creation of a QOL team when the animal is diagnosed with a life-threatening or debilitating chronic condition, or at the time the animal is entered into a terminal study. The team compiles a list of characteristics unique to that individual animal by utilising a questionnaire and a behavioural ethogram. This list enables the team to quantitatively assess any deviations from the established normal behavioural repertoire of that individual. Concurrently, the QOL team determines the number of behavioural deviations that are needed to trigger an immediate discussion of the necessity for humane euthanasia of the animal. The team remains intact once created, and revisits the animal's condition as frequently as deemed necessary. This process improves animal welfare by continuing the quest to optimally define QOL for captive primates, and potentially for all captive animals.

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

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    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.

  15. 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 primate...... models will be an important step in clinical development of cell therapy. Here, we analyzed cynomolgus monkey (CM) iPSC-derived midbrain dopamine neurons for up to 2 years following autologous transplantation in a Parkinson's disease (PD) model. In one animal, with the most successful protocol, we found...... that unilateral engraftment of CM-iPSCs could provide a gradual onset of functional motor improvement contralateral to the side of dopamine neuron transplantation, and increased motor activity, without a need for immunosuppression. Postmortem analyses demonstrated robust survival of midbrain-like dopaminergic...

  16. Detection of antibodies to Oropouche virus in non-human primates in Goiânia City, Goiás

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    Marize Moreira Gibrail

    2016-06-01

    Full Text Available Abstract: INTRODUCTION Arboviruses are associated with human disease, and non-human primates (NHPs are important primary hosts. This study shows the detection of antibodies to Oropouche virus (OROV in NHPs either living in urban parks or acclimatized at the Wild Animal Screening Center, Goiânia city. METHODS: Fifty blood samples were analyzed by hemagglutination-inhibition and neutralization assays. RESULTS: Two monkeys (Alouatta caraya had antibodies to OROV by both techniques. CONCLUSIONS This is the first report demonstrating the detection of OROV antibodies in Goiás State and may represent the introduction/circulation of OROV in the region and a potential risk to the human population.

  17. Evaluation of arboviruses of public health interest in free-living non-human primates (Alouatta spp., Callithrix spp., Sapajus spp. in Brazil

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    Tatiana Carneiro da Rocha

    2015-04-01

    Full Text Available INTRODUCTION: The aim of the present study was to evaluate the presence of arboviruses from the Flavivirus genus in asymptomatic free-living non-human primates (NHPs living in close contact with humans and vectors in the States of Paraná and Mato Grosso do Sul, Brazil. METHODS: NHP sera samples (total n = 80, Alouatta spp. n = 07, Callithrix spp. n = 29 and Sapajus spp. n = 44 were screened for the presence of viral genomes using reverse transcription polymerase chain reaction and 10% polyacrylamide gel electrophoresis techniques. RESULTS: All of the samples were negative for the Flavivirus genome following the 10% polyacrylamide gel electrophoresis analysis. CONCLUSIONS: These negative results indicate that the analyzed animals were not infected with arboviruses from the Flavivirus genus and did not represent a risk for viral transmission through vectors during the period in which the samples were collected.

  18. Is alpha-synuclein loss-of-function a contributor to parkinsonian pathology? Evidence from non-human primates

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    Timothy J Collier

    2016-01-01

    Full Text Available Accumulation of alpha-synuclein (α-syn in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson’s disease (PD, leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous α-syn in dopamine neurons of nonhuman primates reproduces the pattern of nigrostriatal degeneration characteristic of PD.

  19. 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.

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

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    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.

  1. Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

    Science.gov (United States)

    Ma, Kuo-Hsing; Liu, Tsung-Ta; Weng, Shao-Ju; Chen, Chien-Fu F.; Huang, Yuahn-Sieh; Chueh, Sheau-Huei; Liao, Mei-Hsiu; Chang, Kang-Wei; Sung, Chi-Chang; Hsu, Te-Hung; Huang, Wen-Sheng; Cheng, Cheng-Yi

    2016-01-01

    3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate. PMID:27941910

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

    Science.gov (United States)

    Vinot, Nina; Jouin, Mélanie; Lhomme-Duchadeuil, Adrien; Guesnet, Philippe; Alessandri, Jean-Marc; Aujard, Fabienne; Pifferi, Fabien

    2011-01-01

    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, pfatty acids may represent a valuable dietary strategy to improve behavioural and cognitive functions.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Watson, Karli K; Platt, Michael L

    2012-07-30

    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.

  5. Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline.

    Science.gov (United States)

    Kupsch, A; Sautter, J; Götz, M E; Breithaupt, W; Schwarz, J; Youdim, M B; Riederer, P; Gerlach, M; Oertel, W H

    2001-01-01

    The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Monoamine-oxidase B (MAO-B) has been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease, since selegiline (L-deprenyl), an irreversible MAO-B inhibitor, prevents MPTP-induced neurotoxicity in numerous species including mice, goldfish and drosophyla. However, one disadvantage of this substance relates to its metabolism to (-)-methamphetamine and (-)-amphetamine. Rasagiline (R-(+)-N-propyl-1-aminoindane) is a novel irrevesible MAO-B-inhibitor, which is not metabolized to metamphetamine and/or amphetamine. The present study compared the effects of high doses of selegiline and rasagiline (10 mg/kg body weight s.c.) on MPTP-induced dopaminergic neurotoxicity in a non-human primate (Callithrix jacchus) model of PD. Groups of four monkeys were assigned to the following six experimental groups: Group I: Saline, Group II: Selegiline/Saline, Group III: Rasagiline/Saline, Group IV: MPTP/Saline, Group V: Rasagiline/MPTP, Group VI: Selegiline/MPTP. Daily treatment with MAO-B-inhibitors (either rasagiline or selegiline, 10 mg/kg body weight s.c.) was initiated four days prior to MPTP-exposure (MPTP-HCl, 2 mg/kg body weight subcutaneously, separated by an interval of 24 hours for a total of four days) and was continued until the end of the experiment, i.e. 7 days after the cessation of the MPTP-injections, when animals were sacrificed. MPTP-treatment caused distinct behavioural, histological, and biochemical alterations: 1. significant reduction of motor activity assessed by clinical rating and by computerized locomotor activity measurements; 2. substantial loss (approx. 40%) of dopaminergic (tyrosine-hydroxylase-positive) cells in the substantia nigra, pars compacta; and 3. putaminal dopamine depletion of 98% and its metabolites DOPAC (88%) and HVA (96%). Treatment with either rasagiline or selegiline markedly

  6. 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.

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

    Science.gov (United States)

    Basile, Muriel; Lemasson, Alban; Blois-Heulin, Catherine

    2009-07-17

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Effect of palm olein oil in a moderate-fat diet on plasma lipoprotein profile and aortic atherosclerosis in non-human primates.

    Science.gov (United States)

    van Jaarsveld, Paul J; Smuts, Cornelius M; Benadé, A Spinnler

    2002-01-01

    Several studies have reported on the effect of palm olein oil (PO; palmitic acid content approximately 38%) incorporation into the diet on blood cholesterol concentration. Information on the effect of PO on atherosclerosis is, however, lacking. In vervet monkeys (Cercopithecus aethiops), low-density lipoprotein cholesterol (LDL-C) concen-trations can be modulated by the type and amount of fat in the diet. The vervet is a proven model for both the type and composition of human atherosclerotic lesions. The aim of this study was to determine the effect of PO in a moderate-fat moderate-cholesterol diet (MFD) on plasma lipoproteins and the progression of atherosclerosis in a non-human primate model after 25.5 months of dietary exposure. Thirty adult male vervets, never exposed to a Western-type atherogenic diet, were stabilised on a MFD (28%E fat; 26 mg cholesterol/1000 kJ) with a polyunsaturated to saturated fatty acid (P/S) ratio of 0.4 for six weeks. Baseline LDL-C, high-density lipoprotein (HDL)-C and bodyweight were used to stratify the vervets into three comparable groups of 10 each. One group continued with the MFD in which 11.0%E was derived from lard (AF). In the other two groups, the AF was substituted isocalorically with either sunflower oil (SO) or PO. Plasma lipids were measured at 6-monthly intervals and atherosclerosis was assessed in the aorta and in five peripheral arteries after 25.5 months of dietary exposure. The frequency of atherosclerosis in peripheral arteries and aortas was low. PO, relative to SO and AF, significantly reduced the risk for developing early lesions in peripheral arteries (P = 0.0277 and P = 0.0038, respectively) and, relative to AF, in aortas (P = 0.0335). The cholesterolaemic effect of MFD-PO was not significantly different from MFD-SO and MFD-AF. However, at 24 months the plasma total cholesterol concentration with MFD-AF was significantly higher than with MFD-SO (P = 0.0256). It is confirmed that a MFD with PO is no different

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

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    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.

  11. 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

  12. 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.

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

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    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.

  14. Contact to Non-human Primates and Risk Factors for Zoonotic Disease Emergence in the Taï Region, Côte d'Ivoire.

    Science.gov (United States)

    Mossoun, Arsène; Pauly, Maude; Akoua-Koffi, Chantal; Couacy-Hymann, Emmanuel; Leendertz, Siv Aina J; Anoh, Augustin E; Gnoukpoho, Ange H; Leendertz, Fabian H; Schubert, Grit

    2015-12-01

    Elevated exposure levels to non-human primates (NHP) and NHP bushmeat represent major risk factors for zoonotic disease transmission in sub-Saharan Africa. Demography can affect personal nutritional behavior, and thus rates of contact to NHP bushmeat. Here, we analyzed demographic and NHP contact data from 504 participants of differing demographic backgrounds living in proximity to the Taï National Park in Western Côte d'Ivoire (CI) to identify factors impacting the risk of NHP exposure. Overall, participants' contact rates to NHP were high, and increased along a gradient of bushmeat processing (e.g., 7.7% hunted, but 61.9% consumed monkeys). Contact to monkeys was significantly more frequent than to chimpanzees, most likely a reflection of meat availability and hunting effort. 17.2% of participants reported previous interaction with NHP pets. Generalized linear mixed model analysis revealed significant effects of sex, country of birth or ethnicity on rates of NHP bushmeat contact, with male participants from CI being at particular risk of exposure to NHP. The presence of zoonotic pathogens in humans and NHP in Taï further highlights the risk for zoonotic disease emergence in this region. Our results are relevant for formulating prevention strategies to reduce zoonotic pathogen burden in tropical Africa.

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

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    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.

  16. 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.

  17. The MPTP marmoset model of parkinsonism: a multi-purpose non-human primate model for neurodegenerative diseases.

    Science.gov (United States)

    Philippens, Ingrid H C H M; 't Hart, Bert A; Torres, German

    2010-12-01

    Aging societies face an increasing prevalence of neurodegenerative disorders for which no cure exists. The paucity of relevant animal models that faithfully reproduce clinical and pathogenic features of neurodegenerative diseases is a major cause for the lack of effective therapies. Clinically distinct disorders, such as Alzheimer's and Parkinson's disease, are driven by overlapping pathogenic mechanisms that converge onto vulnerable neurons to ultimately cause abnormal clinical outcomes. These similarities, particularly in the early phases of neurodegeneration, might help identify appropriate animal model systems for studying of cell pathology. While reviewing some of the cellular mechanisms of disease progression, we discuss the MPTP-induced model of Parkinsonism in marmoset monkeys as a model system for construct, face and predictive validity in neurodegenerative studies.

  18. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

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    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.

  19. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

    Science.gov (United States)

    Strom, Alexander; Yutzy, Barbara; Kruip, Carina; Ooms, Mark; Schloot, Nanette C; Roden, Michael; Scott, Fraser W; Loewer, Johannes; Holznagel, Edgar

    2014-01-01

    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.

  20. 非人灵长类雌性等级的研究方法%The Methods of Research on the Dominance of Female in Non-human Primates

    Institute of Scientific and Technical Information of China (English)

    赵海涛; 张剑; 朱紫瑞; 李保国; 王晓卫

    2011-01-01

    Socio-ecological theory suggests a link between the rates of agonism, strength of competition for food or safety, reproduction, and structure of dominance hierarchies among group-living females. With research on non-human primates, it is critical to select the method of determining and describing dominance relationships. In the past, research on the Old World monkeys mainly focused on males, with little emphasis on the role of females. However recently, studies focusing on female dominance relationships have attracted more scientific attention. In primatology, the methods to determine dominance hierarchies are very important. Plenty of behavioral standards (such as aggressive-submissive, feeding, carrying infant, grooming etc. ) were used in researching female relationships with results showing varied strategies among different species. Primate social structures are divided into two types: linear hierarchy and partial hierarchy, which can be described using different methods. We followed the " dominance-directed tree" methodology, which is able to detect both types of hierarchy. By summarizing a number of different research studies on dominance, this article presents a methodological standard for determining and describing female dominance relationships.%在非人灵长类动物等级研究中,有关判定与描述优势等级方法的选择至关重要.早期对旧大陆灵长类的等级研究主要关注雄性,对雌性涉猎较少.目前主要应用攻击—屈服、取食、携婴、相互理毛等行为标准来研究灵长类的雌性等级,也发现不同的物种往往有不同的雌性等级模式.依据社群结构的完整性将其分为线性等级与非线性等级,并采用不同的方式进行描述.本文通过查阅文献资料,对雌性等级的研究内容、判定标准以及描述方式进行论述,以便抛砖引玉提高非人灵长类雌性等级的研究水平.

  1. Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

    Directory of Open Access Journals (Sweden)

    Matthew E Downs

    Full Text Available Focused Ultrasound (FUS coupled with intravenous administration of microbubbles (MB is a non-invasive technique that has been shown to reliably open (increase the permeability of the blood-brain barrier (BBB in multiple in vivo models including non-human primates (NHP. This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication. In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.

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

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    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.

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

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    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.

  4. Single oral doses of (±) 3,4-methylenedioxymethamphetamine ('Ecstasy') produce lasting serotonergic deficits in non-human primates: relationship to plasma drug and metabolite concentrations.

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    Mueller, Melanie; Yuan, Jie; McCann, Una D; Hatzidimitriou, George; Ricaurte, George A

    2013-05-01

    Repeated doses of the popular recreational drug methylenedioxymethamphetamine (MDMA, 'Ecstasy') are known to produce neurotoxic effects on brain serotonin (5-HT) neurons but it is widely believed that typical single oral doses of MDMA are free of neurotoxic risk. Experimental and therapeutic trials with MDMA in humans are underway. The mechanisms by which MDMA produces neurotoxic effects are not understood but drug metabolites have been implicated. The aim of the present study was to assess the neurotoxic potential of a range of clinically relevant single oral doses of MDMA in a non-human primate species that metabolizes MDMA in a manner similar to humans, the squirrel monkey. A secondary objective was to explore the relationship between plasma MDMA and metabolite concentrations and lasting serotonergic deficits. Single oral doses of MDMA produced lasting dose-related serotonergic neurochemical deficits in the brains of squirrel monkeys. Notably, even the lowest dose of MDMA tested (5.7 mg/kg, estimated to be equivalent to 1.6 mg/kg in humans) produced significant effects in some brain regions. Plasma levels of MDMA engendered by neurotoxic doses of MDMA were on the order of those found in humans. Serotonergic neurochemical markers were inversely correlated with plasma concentrations of MDMA, but not with those of its major metabolites, 3,4-dihydroxymethamphetamine and 4-hydroxy-3-methoxymethamphetamine. These results suggest that single oral doses of MDMA in the range of those used by humans pose a neurotoxic risk and implicate the parent compound (MDMA), rather than one of its metabolites, in MDMA-induced 5-HT neural injury.

  5. Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates

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    Gastaldelli, Amalia; Casiraghi, Francesca; Halff, Glenn A.; Abrahamian, Gregory A.; Davalli, Alberto M.; Bastarrachea, Raul A.; Comuzzie, Anthony G.; Guardado-Mendoza, Rodolfo; Jimenez-Ceja, Lilia M.; Mattern, Vicki; Paez, Ana Maria; Ricotti, Andrea; Tejero, Mary E.; Higgins, Paul B.; Rodriguez-Sanchez, Iram Pablo; Tripathy, Devjit; DeFronzo, Ralph A.; Dick, Edward J.; Cline, Gary W.; Folli, Franco

    2011-01-01

    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. Aims 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. Methods 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. Results 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. Conclusion 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. PMID:22125617

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

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    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.

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

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    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.

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

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    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.

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

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    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.

  10. Anti-nicotine vaccines: Comparison of adjuvanted CRM197 and Qb-VLP conjugate formulations for immunogenicity and function in non-human primates.

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    McCluskie, Michael J; Thorn, Jennifer; Gervais, David P; Stead, David R; Zhang, Ningli; Benoit, Michelle; Cartier, Janna; Kim, In-Jeong; Bhattacharya, Keshab; Finneman, Jari I; Merson, James R; Davis, Heather L

    2015-12-01

    Anti-nicotine vaccines comprise nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). Unfortunately, those tested clinically have failed to improve overall long term quit rates. We had shown in mice that carrier, hapten, linker, hapten load (number of haptens per carrier molecule), aggregation and adducts, as well as adjuvants influence the function of antibodies (Ab) induced. Herein, we tested an optimized antigen, NIC7-CRM, comprised of 5-aminoethoxy-nicotine (NIC7) conjugated to genetically detoxified diphtheria toxin (CRM197), with hapten load of ~16, no aggregation (~100% monomer) and minimal adducts. NIC7-CRM was tested in non-human primates (NHP) and compared to NIC-VLP, which has the same hapten and carrier as the clinical-stage CYT002-NicQb but a slightly different linker and lower hapten load. With alum as sole adjuvant, NIC7-CRM was superior to NIC-VLP for Ab titer, avidity and ex vivo function (83% and 27% nicotine binding at 40ng/mL respectively), but equivalent for in vivo function after intravenous [IV] nicotine challenge (brain levels reduced ~10%). CpG adjuvant added to NIC7-CRM/alum further enhanced the Ab responses and both ex vivo function (100% bound) and in vivo function (~80% reduction in brain). Thus, both optimal antigen design and CpG adjuvant were required to achieve a highly functional vaccine. The compelling NHP data with NIC7-CRM with alum/CpG supported human testing, currently underway.

  11. Increased Expression of Connective Tissue Growth Factor (CTGF) in Multiple Organs After Exposure of Non-Human Primates (NHP) to Lethal Doses of Radiation.

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

    2015-11-01

    Exposure to sufficiently high doses of ionizing radiation is known to cause fibrosis in many different organs and tissues. Connective tissue growth factor (CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an important role in the development of fibrosis in multiple organs. The aim of the present study was to quantify the gene and protein expression of CTGF in a variety of organs from non-human primates (NHP) that were previously exposed to potentially lethal doses of radiation. Tissues from non-irradiated NHP and NHP exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative reverse transcription PCR, western blot, and immunohistochemistry. Expression of CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung tissues of the non-irradiated NHP. Increased expression of CTGF was also observed in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP; these included the lung, kidney, spleen, thymus, and liver. These irradiated organs also exhibited histological evidence of increased collagen deposition compared to the control tissues. There was significant correlation of CTGF expression with collagen deposition in the lung and spleen of NHP exposed to PBI/BM5. Significant correlations were observed between spleen and multiple organs on CTGF expression and collagen deposition, respectively, suggesting possible crosstalk between spleen and other organs. These data suggest that CTGF levels are increased in multiple organs after radiation exposure and that inflammatory cell infiltration may contribute to the elevated levels of CTGF in multiple organs.

  12. Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates

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    Wang Jinkai

    2012-08-01

    Full Text Available Abstract Background The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. Results To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Conclusions Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

  13. Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe-affected non-human primates by intracerebral lentiviral gene therapy.

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    Meneghini, Vasco; Lattanzi, Annalisa; Tiradani, Luigi; Bravo, Gabriele; Morena, Francesco; Sanvito, Francesca; Calabria, Andrea; Bringas, John; Fisher-Perkins, Jeanne M; Dufour, Jason P; Baker, Kate C; Doglioni, Claudio; Montini, Eugenio; Bunnell, Bruce A; Bankiewicz, Krystof; Martino, Sabata; Naldini, Luigi; Gritti, Angela

    2016-05-02

    Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively. Our previous studies established lentiviral gene therapy (GT) as a rapid and effective intervention to provide pervasive supply of therapeutic lysosomal enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this strategy is similarly effective in juvenile non-human primates (NHP). To provide proof of principle for tolerability and biological efficacy of the strategy, we established a comprehensive study in normal NHP delivering a clinically relevant lentiviral vector encoding for the human ARSA transgene. Then, we injected a lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus macaques, evaluating for the first time the therapeutic potential of lentiviral GT in this unique LSD model. We showed favorable safety profile and consistent pattern of LV transduction and enzyme biodistribution in the two models, supporting the robustness of the proposed GT platform. We documented moderate inflammation at the injection sites, mild immune response to vector particles in few treated animals, no indication of immune response against transgenic products, and no molecular evidence of insertional genotoxicity. Efficient gene transfer in neurons, astrocytes, and oligodendrocytes close to the injection sites resulted in robust production and extensive spreading of transgenic enzymes in the whole CNS and in CSF, leading to supraphysiological ARSA activity in normal NHP and close to physiological GALC activity in the Krabbe NHP, in which biological efficacy was associated with preliminary indication of therapeutic benefit. These results support the rationale for the clinical translation of intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other neurodegenerative LSD.

  14. HemaMax™, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates.

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    Lena A Basile

    Full Text Available HemaMax, a recombinant human interleukin-12 (IL-12, is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12, and HemaMax to increase survival after total body irradiation (TBI in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8-9 Gy (p<0.05 Pearson's chi-square test. This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit-expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg administered at 24 hours after TBI (6.7 Gy/LD(50/30 significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test. This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes, thrombocyte, and reticulocyte counts during nadir (days 12-14 and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting

  15. 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.

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

    Science.gov (United States)

    Cong, Yu; McArthur, Monica A; Cohen, Melanie; Jahrling, Peter B; Janosko, Krisztina B; Josleyn, Nicole; Kang, Kai; Zhang, Tengfei; Holbrook, Michael R

    2016-05-01

    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.

  17. Atypical BSE (BASE transmitted from asymptomatic aging cattle to a primate.

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    Emmanuel E Comoy

    Full Text Available BACKGROUND: Human variant Creutzfeldt-Jakob Disease (vCJD results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE. Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains. METHODOLOGY/PRINCIPAL FINDINGS: Brain homogenates from cattle with classical BSE and atypical (BASE infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis, a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres. The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine. CONCLUSION/SIGNIFICANCE: Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.

  18. An Overview on Selection and Usage of Sleeping Sites in Non-Human Primates%非人灵长类动物睡眠地点的选择与利用

    Institute of Scientific and Technical Information of China (English)

    王铭; 赵大鹏; 张剑; 李保国

    2009-01-01

    睡眠行为在非人灵长类动物的生活史中占有十分重要地位.关于非人灵长类睡眠地点选择与利用的研究是灵长类行为生态学领域的核心课题之一.本文回顾以往的研究,总结了非人灵长类动物睡眠地点选择的三个主要影响因素,即捕食压力引起的安全因素,睡眠地点的舒适因素和卫生因素;分别对非人灵长类睡眠地点选择的三种主要形式进行了初步的成因讨论,对未来的研究方向进行探索性地展望.%Sleeping behavior is a necessary life-sustaining activity for non-human primates, but is especially important in the life history of these animals because they spend approximately half of their lifetime sleeping. After a retrospective literature overview, we found that security (imposed by predation pressure) , comfort and sanitation are the main factors affecting the selection and utilization of sleeping site by non-human primates. Non-human primates generally display three different choices of sleep site selection, which include arboreal, ground and nesting. By way of conclusion we discuss the differences between species and related environmental effects. The present paper also provides several promising directions for further research .

  19. Aging in the natural world: comparative data reveal similar mortality patterns across primates.

    Science.gov (United States)

    Bronikowski, Anne M; Altmann, Jeanne; Brockman, Diane K; Cords, Marina; Fedigan, Linda M; Pusey, Anne; Stoinski, Tara; Morris, William F; Strier, Karen B; Alberts, Susan C

    2011-03-11

    Human senescence patterns-late onset of mortality increase, slow mortality acceleration, and exceptional longevity-are often described as unique in the animal world. Using an individual-based data set from longitudinal studies of wild populations of seven primate species, we show that contrary to assumptions of human uniqueness, human senescence falls within the primate continuum of aging; the tendency for males to have shorter life spans and higher age-specific mortality than females throughout much of adulthood is a common feature in many, but not all, primates; and the aging profiles of primate species do not reflect phylogenetic position. These findings suggest that mortality patterns in primates are shaped by local selective forces rather than phylogenetic history.

  20. Teeth, sex, and testosterone: aging in the world's smallest primate.

    Directory of Open Access Journals (Sweden)

    Sarah Zohdy

    Full Text Available Mouse lemurs (Microcebus spp. are an exciting new primate model for understanding human aging and disease. In captivity, Microcebus murinus develops human-like ailments of old age after five years (e.g., neurodegeneration analogous to Alzheimer's disease but can live beyond 12 years. It is believed that wild Microcebus follow a similar pattern of senescence observed in captive animals, but that predation limits their lifespan to four years, thus preventing observance of these diseases in the wild. Testing whether this assumption is true is informative about both Microcebus natural history and environmental influences on senescence, leading to interpretation of findings for models of human aging. Additionally, the study of Microcebus longevity provides an opportunity to better understand mechanisms of sex-biased longevity. Longevity is often shorter in males of species with high male-male competition, such as Microcebus, but mouse lemurs are sexually monomorphic, suggesting similar lifespans. We collected individual-based observations of wild brown mouse lemurs (Microcebus rufus from 2003-2010 to investigate sex-differences in survival and longevity. Fecal testosterone was measured as a potential mechanism of sex-based differences in survival. We used a combination of high-resolution tooth wear techniques, mark-recapture, and hormone enzyme immunoassays. We found no dental or physical signs of senescence in M. rufus as old as eight years (N = 189, ages 1-8, mean = 2.59 ± 1.63 SE, three years older than captive, senescent congeners (M. murinus. Unlike other polygynandrous vertebrates, we found no sex difference in age-dependent survival, nor sex or age differences in testosterone levels. While elevated male testosterone levels have been implicated in shorter lifespans in several species, this is one of the first studies to show equivalent testosterone levels accompanying equivalent lifespans. Future research on captive aged individuals can

  1. 非人灵长类动物异常行为与5-HTTLPR关系研究进展%Advances research on relationship between abnormal behavior and 5-HTTLPR in non--human primates

    Institute of Scientific and Technical Information of China (English)

    黄璋琼; 孙晓梅; 叶尤松; 江勤芳; 代解杰

    2011-01-01

    非人灵长类动物饲养环境被改变或受到控制时将会干扰动物作出正常反应,常表现出许多异常行为(abnormal behavior),与人类相似,这些异常行为多是心理疾患的具体表现,人和非人灵长类动物的异常行为是遗传因素和环境因素相互作用的结果,其中遗传因素是指5-HTTLPR.现将近年来有关非人灵长类动物异常行为与5-HTTLPR多态性的关系进展作一概述.%When breeding environment changed or under constraint, the rhesus macaque reaction could be interfered,might result in some abnormal behaviors. Similar to human - beings, these behaviors are manifestation of psychological diseases , abnormal behaviors of human - beings and non - human primates were interaction results of genetic factors and environment factors. Genetic facror was 5 - HTTLPR. Now we summarize the advances research of relationship between ahnormal behaviors of non - human primates and 5 - HTTLPR polymorphism

  2. Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus.

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    Marine Joly

    Full Text Available Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD and reversal learning (PDR tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research.

  3. Touchscreen-based cognitive tasks reveal age-related impairment in a primate aging model, the grey mouse lemur (Microcebus murinus).

    Science.gov (United States)

    Joly, Marine; Ammersdörfer, Sandra; Schmidtke, Daniel; Zimmermann, Elke

    2014-01-01

    Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research.

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

    Science.gov (United States)

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

    2017-04-06

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

  5. The active metabolite of prasugrel, R-138727, improves cerebral blood flow and reduces cerebral infarction and neurologic deficits in a non-human primate model of acute ischaemic stroke.

    Science.gov (United States)

    Sugidachi, Atsuhiro; Mizuno, Makoto; Ohno, Kousaku; Jakubowski, Joseph A; Tomizawa, Atsuyuki

    2016-10-05

    Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits.

  6. 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.

  7. 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.

  8. 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.

  9. Estudo anatômico do osso temporal de um primata não-humano (Callithrix sp Anatomical study of a temporal bone from a non-human primate (Callithrix sp

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    Andrei Borin

    2008-06-01

    Full Text Available A busca por modelos experimentais constitui passo fundamental para o avanço da medicina. OBJETIVO: Demonstrar, através da dissecção com técnicas microcirúrgicas, as estruturas anatômicas do osso temporal do primata Callithrix sp. FORMA DE ESTUDO: Experimental. MÉTODO: Dissecção de ossos temporais de Callithrix sp e documentação fotográfica. RESULTADOS: Identificamos as principais estruturas do osso temporal (orelhas externa, média e interna, e nervo facial. CONCLUSÃO: O primata não-humano Callithrix sp representa aparentemente um modelo viável para o estudo do osso temporal uma vez que apresenta alta similaridade anatômica com humanos.The search for experimental (animal models is essential to the development of clinical studies. AIM: To demonstrate, by means of micro dissection techniques, the anatomical structures of temporal bones from the primate Callithrix sp. STUDY DESIGN: Experimental. METHODS: Dissection of temporal bone structures of Callithrix sp and photographic documentation. RESULTS: We identified the main constituents of the temporal bone (external, medium and inner ear and facial nerve. CONCLUSION: The non-human primate Callithrix sp. is an adequate experimental model for the studies of temporal bone structures given its close anatomical similarities to that found in humans.

  10. 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

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

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    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.

  12. Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged Gastrointestinal Injury.

    Science.gov (United States)

    Jones, Jace W; Bennett, Alexander; Carter, Claire L; Tudor, Gregory; Hankey, Kim G; Farese, Ann M; Booth, Catherine; MacVittie, Thomas J; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for acute and prolonged gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV LINAC-derived photons; 0.80 Gy min) in nonhuman primate models was investigated. The irradiation exposure covered gastrointestinal injuries spanning lethal, mid-lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via measurement of plasma citrulline and small intestinal histopathology over the first 15 d following radiation exposure and included total-body irradiation at 13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy partial-body irradiation included time points out to day 60 and day 180, respectively, which allowed for correlation of plasma citrulline to prolonged gastrointestinal injury and survival. Plasma citrulline values were radiation-dependent for all radiation doses under consideration, with nadir values ranging from 63-80% lower than radiation-naïve NHP plasma. The nadir values were observed at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles demonstrated prolonged gastrointestinal injury resulting from acute high-dose irradiation had long lasting effects on enterocyte function. Moreover, plasma citrulline did not discriminate between total-body or partial-body irradiation over the first 15 d following irradiation and was not predictive of survival based on the radiation models considered herein.

  13. 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

  14. Micro-MRI study of cerebral aging: ex vivo detection of hippocampal subfield reorganization, microhemorrhages and amyloid plaques in mouse lemur primates.

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    Anne Bertrand

    Full Text Available Mouse lemurs are non-human primate models of cerebral aging and neurodegeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 µm in-plane resolution. First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon's horn. We show that both dentate gyrus and Ammon's horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon's horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral microhemorrhages.

  15. An Evaluation of 20 Years of EU Framework Programme-Funded Immune-Mediated Inflammatory Translational Research in Non-Human Primates

    NARCIS (Netherlands)

    Haanstra, Krista G.; Jonker, Margreet; 't Hart, Bert A.

    2016-01-01

    Aging 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 decr

  16. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  17. Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases

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    Jean-Michel eVERDIER

    2015-03-01

    Full Text Available Animal models are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates. Beside the fact that their brain structure is much closer to that of humans, they develop highly complex cognitive strategies and they are visually-oriented like humans. For these reasons, they deserve consideration, although their management and care are more complicated and the related costs much higher. Despite these caveats, considerable scientific advances have been possible using nonhuman primates. This review concisely summarizes their role in the study of aging and of the mechanisms involved in neurodegenerative disorders associated mainly with cognitive dysfunctions (Alzheimer’s and prion diseases or motor deficits (Parkinson’s and related diseases.

  18. Cardiac safety profile of etamicastat, a novel peripheral selective dopamine-β-hydroxylase inhibitor in non-human primates, human young and elderly healthy volunteers and hypertensive patients

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    Manuel Vaz-da-Silva

    2015-06-01

    Full Text Available The aim of this work was to evaluate the cardiac risk for etamicastat, a peripheral reversible dopamine-β-hydroxylase inhibitor. Etamicastat blocked the hERG current amplitude with an IC50 value of 44 μg/ml. Etamicastat had no substantial effects on arterial blood pressure, heart rate and the PR interval in male Cynomolgus monkeys when administered orally up to 90 mg/kg. Administered orally at 15 and 45 mg/kg/day in female and male Cynomolgus monkey for 91 days, etamicastat had no effect on heart rate and the waveform or intervals of the electrocardiogram. At the highest dose level of 45 mg/kg, mean plasma concentrations of etamicastat ranged from 1875 to 3145 ng/ml on Day 1 and Day 91 of treatment, respectively. The effect of age on the tolerability and pharmacokinetics of etamicastat in elderly (≥65 years and young adult (18–45 years subjects showed that supine systolic (SBP and diastolic (DBP blood pressure, ECG heart rate, PR interval, QRS duration and QTcF interval were not affected following once-daily administration of 100 mg/day etamicastat for 7 days. In hypertensive patients the decrease of blood pressure tended to be more important in subjects who had received etamicastat (50, 100 and 200 mg than in subjects who had received placebo. No clinically significant out-of-range values in vital signs or ECG parameters, ECG heart rate, PR interval, QRS duration and QTcF interval were observed in hypertensive subjects following once-daily administration of etamicastat for 10 days. In conclusion, etamicastat is not likely to prolong the QT interval at therapeutic doses.

  19. 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.

  20. Cell enrichment-free massive ex-vivo expansion of peripheral CD20⁺ B cells via CD40-CD40L signals in non-human primates.

    Science.gov (United States)

    Kim, Jung-Sik; Byun, Nari; Chung, Hyunwoo; Kim, Hyun-Je; Kim, Jong-Min; Chun, Taehoon; Lee, Won-Woo; Park, Chung-Gyu

    2016-04-22

    Non-human primates (NHPs) are valuable as preclinical resources that bridge the gap between basic science and clinical application. B cells from NHPs have been utilized for the development of B-cell targeted drugs and cell-based therapeutic modalities; however, few studies on the ex-vivo expansion of monkey B cells have been reported. In this study, we developed a highly efficient ex-vivo expansion protocol for monkey B cells resulting in 99% purity without the requirement for prior cell-enrichment procedures. To this end, monkey peripheral blood mononuclear cells (PBMCs) were stimulated for 12 days with cells constitutively expressing monkey CD40L in expansion medium optimized for specific and massive expansion of B cells. The B cells expansion rates obtained were 2-5 times higher than those previously reported in humans, with rates ranging from 7.9 to 16.6 fold increase. Moreover, expanded B cells sustained high expression of co-stimulatory molecules including CD83 and CD86 until day 12 of culture, and the simple application of a brief centrifugation resulted in a CD20(+) B cell purity rate of greater than 99%. Furthermore, small amounts of CD3(+)CD20(+)BT-like cells were generated and CD16 was expressed at moderate levels on expanded B cells. Thus, the establishment of this protocol provides a method to produce quantities of homogeneous, mature B cells in numbers sufficient for the in vitro study of B cell immunity as well as for the development of B cell-diagnostic tools and cell-based therapeutic modalities.

  1. 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.

  2. Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. In vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lymphocytes of venous blood from man and a non-human primate (Callithrix jacchus)

    Energy Technology Data Exchange (ETDEWEB)

    Neubert, R.; Helge, H. (Freie Univ. Berlin (Germany, F.R.). Kinderklinik und Poliklinik); Jacob-Mueller, U.; Stahlmann, R.; Neubert, D. (Freie Univ. Berlin (Germany, F.R.). Inst. fuer Toxikologie und Embryonalpharmakologie)

    1991-04-01

    The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on poke weed mitogen-stimulated proliferation and differentiation of peripheral lymphocytes was studied in vitro with cells from a non-human primate (marmoset monkey, Callithrix jacchus) and from man. Monoclonal antibodies and flow cytometry (FACScan) were used for analysis. The extent of the overall mitogen-stimulated proliferation of isolated lymphocytes in vitro from marmoset blood was only slightly reduced in the presence of TCDD compared to the solvent control (0.01% DMSO). However, incubation with TCDD in the culture medium together with the mitogen led to a pronounced decrease in the percentage of the lymphocyte subset with the surface marker CD4, and a concomitant increase in the percentage of CD8{sup +} cells. The lowest concentration found to be effective in vitro was 1x10{sup -13} M TCDD (25 fg TCDD/ml). When culturing lymphocytes from human blood of different donors under indentical conditions in the presence of TCDD and the mitogen, corresponding effects were observed to those seen with marmoset cells. A closer analysis of the T lymphocyte subsets affected revealed the CD4{sup +}CDw29{sup +} (helper-inducer cells) to be the main target for the action of TCDD. A clear-cut change in the percentage of this subpopulation was induced at concentrations as low as 1x10{sup -13} M TCDD. The development of the IL-2-marker in culture was only slightly affected by TCDD, and concentrations of 1x10{sup -12} M were required to slightly reduce the number of CD2{sup +}CD25{sup +} cells. Special B cells, namely CD20{sup +} (i.e. B{sub 1}) cells, were found to be especially susceptible to the action of TCDD, and clear-cut effects were seen in several experimental series at 1x10{sup -14} M TCDD. The formation of B cells with IgG lambda or kappa chains was also depressed in culture in the presence of TCDD. (orig./MG).

  3. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Picq

    Full Text Available The mouse lemur (Microcebus murinus is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12 and aged (n = 8 adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.

  4. 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

    Directory of Open Access Journals (Sweden)

    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

  5. Memory impairment in aged primates is associated with region-specific network dysfunction

    Science.gov (United States)

    Thomé, Alexander; Gray, Daniel T.; Erickson, Cynthia A.; Lipa, Peter; Barnes, Carol A.

    2015-01-01

    Age-related deficits in episodic memory result, in part, from declines in the integrity of medial temporal lobe structures, such as the hippocampus, but are not thought to be due to widespread loss of principal neurons. Studies in rodents suggest, however, that inhibitory interneurons may be particularly vulnerable in advanced age. Optimal encoding and retrieval of information depend on a balance of excitatory and inhibitory transmission. It is not known whether a disruption of this balance is observed in aging nonhuman primates, and whether such changes affect network function and behavior. To examine this question we combine large scale electrophysiological recordings with cell type-specific imaging in the medial temporal lobe of cognitively-assessed, aged rhesus macaques. We found that neuron excitability in hippocampal region CA3 is negatively correlated with the density of the somatostatin-expressing inhibitory interneurons in the vicinity of the recording electrodes in stratum oriens. By contrast, no hyperexcitability or interneuron loss was observed in the perirhinal cortex of these aged, memory-impaired monkeys. These data provide a link, for the first time, between selective increases in principal cell excitability and declines in a molecularly-defined population of interneurons that regulate network inhibition. PMID:26503764

  6. Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates

    Directory of Open Access Journals (Sweden)

    Xue-mei Zhang

    2009-10-01

    Full Text Available A novel population of cells that express typical immature neuronal markers including doublecortin (DCX+ has been recently identified throughout the adult cerebral cortex of relatively large mammals (guinea pig, rabbit, cat, monkey and human. These cells are more common in the associative relative to primary cortical areas and appear to develop into interneurons including type II nitrinergic neurons. Here we further describe these cells in the cerebral cortex and amygdala, in comparison with DCX+ cells in the hippocampal dentate gyrus, in 3 age groups of rhesus monkeys: young adult (12.3±0.2 yrs, n=3, mid-age (21.2±1.9 yrs, n=3 and aged (31.3±1.8 yrs, n=4. DCX+ cells with a heterogeneous morphology persisted in layers II/III primarily over the associative cortex and amygdala in all groups (including in two old animals with cerebral amyloid pathology, showing a parallel decline in cell density with age across regions. In contrast to the cortex and amygdala, DCX+ cells in the subgranular zone diminished in the mid-age and aged groups. DCX+ cortical cells might arrange as long tangential migratory chains in the mid-age and aged animals, with apparently distorted cell clusters seen in the aged group. Cortical DCX+ cells colocalized commonly with polysialylated neural cell adhesion molecule (PSA-NCAM and partially with neuron-specific nuclear protein (NeuN and γ-aminobutyric acid (GABA, suggesting a potential differentiation of these cells into interneuron phenotype. These data suggest a life-long role for immature interneuron-like cells in the associative cerebral cortex and amygdala in nonhuman primates.

  7. Does the use of the dynamic system approach really help fill in the gap between human and non human primate language ? Commentary to S. Shanker and B. J. King " the Emergence of a New Paradigm in Ape Language Research"

    OpenAIRE

    2002-01-01

    The highly recommended transposition of the dynamic system approach for tackling the question of apes’ linguistic abilities has clearly not led to a demonstration that these primates have acquired language. Fundamental differences related to functional modalities – namely, use of the declarative and the form of engagement between mother and infant –can be observed in the way humans and apes use their communicatory systems.

  8. Age and sex-specific mortality of wild and captive populations of a monogamous pair-bonded primate (Aotus azarae)

    DEFF Research Database (Denmark)

    Larson, Sam; Colchero, Fernando; Jones, Owen

    2016-01-01

    In polygynous primates, a greater reproductive variance in males has been linked to their reduced life expectancy relative to females. The mortality patterns of monogamous pair-bonded primates, however, are less clear. We analyzed the sex differences in mortality within wild (NMales = 70, NFemales...... were best fit by the logistic and Gompertz models respectively, implying greater heterogeneity in the wild environment likely due to harsher conditions. We found that age patterns of mortality were similar between the sexes in both populations. We calculated life expectancy and disparity, the latter...... a measure of the steepness of senescence, for both sexes in each population. Males and females had similar life expectancies in both populations; the wild population overall having a shorter life expectancy than the captive one. Furthermore, captive females had a reduced life-disparity relative to captive...

  9. Old world monkeys and new age science: the evolution of nonhuman primate systems virology.

    Science.gov (United States)

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

    2013-01-01

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

  10. Capillary changes in hippocampal CA1 and CA3 areas of the aging rhesus monkey

    NARCIS (Netherlands)

    Keuker, JIH; Luiten, PGM; Fuchs, E

    2000-01-01

    The rhesus monkey is considered a useful animal model for studying human aging, because non-human primates show many of the neurobiological alterations that have been reported in aging humans. Cognitive impairment that accompanies normal aging may, at least partially, originate from capillary change

  11. CRISPR/Cas9系统:构建非人灵长类动物疾病模型的新技术%CRISPR/Cas9 system:a new gene modification tool for establishing disease models in non-human primates

    Institute of Scientific and Technical Information of China (English)

    杨伟莉; 涂著池; 李晓江

    2014-01-01

    动物疾病模型在研究人类疾病致病机理和药物筛选中起到了关键作用。非人灵长类动物由于与人类更为接近,在探究人类神经退行性疾病、神经精神疾病及人类认知功能、神经环路等方面具有巨大的优势可成为研究和药物筛选的重要疾病模型。然而,由于缺乏大动物的胚胎干细胞系,传统的基因打靶技术难于用来建立灵长类动物疾病模型。最近发展的基因编辑新技术 CRISPR /Cas9系统在定向对基因进行修饰上展现出了巨大的潜力。本文将介绍 CRISPR /Cas9技术的发展和应用,以及非灵长类动物作为神经退行性疾病模型的优势和意义。%Animal models are highly valuable systems that have been extensively used to elucidate human disease pathogenesis and to find therapeutic ways to treat human diseases .Since non-human primates are close to humans,monkeys are important model species in exploring the mechanisms and treatment of human neurodegenerative diseases , neuropsychiatric disorders, cognitive function, and neural circuits.However, due to the lack of embryonic stem cell lines in large animals, the traditional gene targeting technology is difficult to establish primate animal models of human diseases . CRISPR/Cas9, as a recently developed tool for genome modifications , has been successfully used to target genomic loci in mouse, rat, monkey, and other species.Here, we discuss the utilization of CRISPR /Cas9 technology in establishing monkey models for studying human neurodegenerative diseases .

  12. 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

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

    Science.gov (United States)

    Grandi, Laura C.

    2016-01-01

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

  14. Sporadic premature aging in a Japanese monkey: a primate model for progeria.

    Science.gov (United States)

    Oishi, Takao; Imai, Hiroo; Go, Yasuhiro; Imamura, Masanori; Hirai, Hirohisa; Takada, Masahiko

    2014-01-01

    In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

  15. Sporadic premature aging in a Japanese monkey: a primate model for progeria.

    Directory of Open Access Journals (Sweden)

    Takao Oishi

    Full Text Available In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

  16. A simpler primate brain: the visual system of the marmoset monkey.

    Science.gov (United States)

    Solomon, Samuel G; Rosa, Marcello G P

    2014-01-01

    Humans are diurnal primates with high visual acuity at the center of gaze. Although primates share many similarities in the organization of their visual centers 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 aging. 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 organization 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.

  17. Animal models of age related macular degeneration

    OpenAIRE

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  18. Visual recognition of age class and preference for infantile features: implications for species-specific vs universal cognitive traits in primates.

    Directory of Open Access Journals (Sweden)

    Anna Sato

    Full Text Available Despite not knowing the exact age of individuals, humans can estimate their rough age using age-related physical features. Nonhuman primates show some age-related physical features; however, the cognitive traits underlying their recognition of age class have not been revealed. Here, we tested the ability of two species of Old World monkey, Japanese macaques (JM and Campbell's monkeys (CM, to spontaneously discriminate age classes using visual paired comparison (VPC tasks based on the two distinct categories of infant and adult images. First, VPCs were conducted in JM subjects using conspecific JM stimuli. When analyzing the side of the first look, JM subjects significantly looked more often at novel images. Based on analyses of total looking durations, JM subjects looked at a novel infant image longer than they looked at a familiar adult image, suggesting the ability to spontaneously discriminate between the two age classes and a preference for infant over adult images. Next, VPCs were tested in CM subjects using heterospecific JM stimuli. CM subjects showed no difference in the side of their first look, but looked at infant JM images longer than they looked at adult images; the fact that CMs were totally naïve to JMs suggested that the attractiveness of infant images transcends species differences. This is the first report of visual age class recognition and a preference for infant over adult images in nonhuman primates. Our results suggest not only species-specific processing for age class recognition but also the evolutionary origins of the instinctive human perception of baby cuteness schema, proposed by the ethologist Konrad Lorenz.

  19. Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.

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    Ronza Abdel Rassoul

    Full Text Available Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD. However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix. Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented ß-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays, we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA. ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in "AD-like" animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group. Functional categorization showed that most of the genes that were up-regulated in healthy old animals and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in "AD-like" animals. These results open

  20. 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.

  1. 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

  2. Tree shrews at the German Primate Center

    OpenAIRE

    Fuchs, E

    2015-01-01

    For many years, Tupaia (family Tupaiidae), most commonly known as tree shrews, have been studied almost exclusively by zoologists resulting in a controversial debate on their taxonomic status among mammals. Today, tree shrews are placed in the order Scandentia; they are valuable, widely accepted and increasingly used model animals as an alternative to rodents and non-human primates in biomedical research. After a brief description on how tree shrews entered science and their...

  3. The ecology of primate material culture.

    Science.gov (United States)

    Koops, Kathelijne; Visalberghi, Elisabetta; van Schaik, Carel P

    2014-11-01

    Tool use in extant primates may inform our understanding of the conditions that favoured the expansion of hominin technology and material culture. The 'method of exclusion' has, arguably, confirmed the presence of culture in wild animal populations by excluding ecological and genetic explanations for geographical variation in behaviour. However, this method neglects ecological influences on culture, which, ironically, may be critical for understanding technology and thus material culture. We review all the current evidence for the role of ecology in shaping material culture in three habitual tool-using non-human primates: chimpanzees, orangutans and capuchin monkeys. We show that environmental opportunity, rather than necessity, is the main driver. We argue that a better understanding of primate technology requires explicit investigation of the role of ecological conditions. We propose a model in which three sets of factors, namely environment, sociality and cognition, influence invention, transmission and retention of material culture.

  4. [Experimental whooping cough of nonhuman primate].

    Science.gov (United States)

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

    2013-01-01

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

  5. Age-Related Changes in the Central Nervous System in Selected Domestic Mammals and Primates

    Directory of Open Access Journals (Sweden)

    Maciej Firląg

    2013-04-01

    Full Text Available Aging is a process which operates at many levels of physiological, genetic and molecular organizationand leads inevitably to death [18]. Brain macroscopic changes by MRI investigation during aging were observed in humans and dogs but chimpanzees did not display significant changes. This suggestion led to the statement that brain aging is different in various species. Although human brain changes, e.g. β-amyloid storage, neurofibrillary tangle formation, lipofuscin, are relatively well known, we are still looking for a suitable animal model to study the mechanisms of aging and neurodegenerative diseases. Therefore, this paper presents a comparative analysis of the changes described in the brains of senile dog, horse and gorilla. In addition we present the latest, non-invasive methods that can be applied in the diagnosisof old age in mammals. Our considerations have shown that the best animal model for further studies and observations on aging is the dog. 

  6. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    Science.gov (United States)

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-10-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

  7. Magnetic resonance imaging in primates. The example of the mouse lemur (Microcebus murinus: From detection of pathological aging to therapeutic evaluations Imagerie par résonance magnétique chez les primates. L’exemple du microcèbe murin (Microcebus murinus : De la détection du vieillissement cérébral pathologique à l'évaluation thérapeutique

    Directory of Open Access Journals (Sweden)

    Nadine El Tannir El Tayara

    2011-02-01

    Full Text Available Cerebral aging is a major public health issue in our societies as the aged population increases dramatically. It leads in many cases to neurodegenerative diseases such as Alzheimer disease (AD. Rodents and particularly transgenic mice are widely used as models for research on physiopathology of cerebral aging, neurodegenerative diseases and for the evaluation of therapies. However these models do not mimic all the pathophysiological aspects of human diseases. Complementary models such as non-human primates are phylogenetically close to humans and thus more predictive of drug efficiency in humans. Mouse lemur (Microcebus murinus is a small primate (about 12cm, 100g described as a useful model of cerebral aging and as a potential model of AD. Indeed several animals develop age-associated cerebral alterations like amyloidosis and other cerebral changes. Non invasive medical imaging methods such as magnetic resonance imaging (MRI can be used to follow-up brain changes in these animals. In this review, we present how mouse lemurs can be followed-up by MRI and how MRI can be used during therapeutic evaluations and other applications in this model. MR images can be used to follow-up cerebral anatomy in mouse lemurs. It allows for the description of age-associated atrophic processes, age-associated iron accumulation, and vascular anatomy (thanks to MR angiography. Cerebral glucose uptake can be studied in mouse lemurs with other in vivo imaging modalities such as positron emission tomography (PET. In this case, MRI can be used as a support for quantification of radioligand uptake in specific structures. Ex vivo MR imaging is another MR protocol that can be used to describe cerebral aging in lemurs. It provides high resolution 3D histological brain images and allows for studying exquisite anatomical details or microhemorrhages. Finally, MRI can be used to practice cerebral surgery in lemurs and determine coordinates for stereotactic injections. It can

  8. Poor Memory Performance in Aged Cynomolgus Monkeys with Hippocampal Atrophy, Depletion of Amyloid Beta 1-42 and Accumulation of Tau Proteins in Cerebrospinal Fluid

    DEFF Research Database (Denmark)

    Darusman, Huda S; Pandelaki, Jacub; Mulyadi, Rahmad

    2014-01-01

    , aged cynomolgus monkeys were divided into two groups to compare high-performing (n=6) and low-performing (n=6) subjects. Both groups were tested for biomarkers related to Alzheimer's disease and their brains were scanned using structural magnetic resonance imaging. RESULTS: The subjects with poor DRT......-impaired Cynomolgus monkeys may be useful as a spontaneous non-human primate model for investigations of age-related neurodegenerative diseases....

  9. 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.

  10. Enrichment and aggression in primates.

    Science.gov (United States)

    Honess, P E; Marin, C M

    2006-01-01

    There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.

  11. 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

  12. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007......) 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...

  13. Detection of arboviruses of public health interest in free-living New World primates (Sapajus spp.; Alouatta caraya) captured in Mato Grosso do Sul, Brazil.

    OpenAIRE

    2014-01-01

    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 Eva...

  14. 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.

  15. 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…

  16. 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

    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

  17. Raptors and primate evolution.

    Science.gov (United States)

    McGraw, W Scott; Berger, Lee R

    2013-01-01

    Most scholars agree that avoiding predators is a central concern of lemurs, monkeys, and apes. However, given uncertainties about the frequency with which primates actually become prey, the selective importance of predation in primate evolution continues to be debated. Some argue that primates are often killed by predators, while others maintain that such events are relatively rare. Some authors have contended that predation's influence on primate sociality has been trivial; others counter that predation need not occur often to be a powerful selective force. Given the challenges of documenting events that can be ephemeral and irregular, we are unlikely ever to amass the volume of systematic, comparative data we have on such topics as feeding, social dynamics, or locomotor behavior. Nevertheless, a steady accumulation of field observations, insight gained from natural experiments, and novel taphonomic analyses have enhanced understanding of how primates interact with several predators, especially raptors, the subject of this review.

  18. Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

    Science.gov (United States)

    2015-10-01

    vascularized bone marrow component that could be clearly seen; the NHP Pathology report showed that the animal had developed post-transplant...days post-transplant with neither clinical nor histological evidence of rejection (Figure 3). The animal developed a suspicious looking lesion around...Model in Non-Human Primates. Oral Presentation. New England Society of Plastic & Reconstructive Surgeons. Sebasco, Maine. June 2014. Leonard DA

  19. Transgenic Primate Research Paves the Path to a Better Animal Model: Are We a Step Closer to Curing Inherited Human Genetic Disorders?

    Institute of Scientific and Technical Information of China (English)

    Anthony W.S. Chan

    2009-01-01

    While the advancement of transgenic primate models has led to a new era in modeling human conditions and has a clear impact on elucidating the mechanism of human genetic diseases, some thoughts should be considered if non-human primates are the appropriate model.

  20. Biologic data of Macaca mulatta, Macaca fascicularis, and Saimiri sciureusused for research at the fiocruz primate center

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Ribeiro Andrade

    2004-10-01

    Full Text Available Physiological parameters of laboratory animals used for biomedical research is crucial for following several experimental procedures. With the intent to establish baseline biologic parameters for non-human primates held in closed colonies, hematological and morphometric data of captive monkeys were determined. Data of clinically healthy rhesus macaques (Macaca mulatta, cynomolgus monkeys (Macaca fascicularis, and squirrel monkeys (Saimiri sciureus were collected over a period of five years. Animals were separated according to sex and divided into five age groups. Hematological data were compared with those in the literature by Student's t test. Discrepancies with significance levels of 0.1, 1 or 5% were found in the hematological studies. Growth curves showed that the sexual dimorphism of rhesus monkeys appeared at an age of four years. In earlier ages, the differences between sexes could not be distinguished (p < 0.05. Sexual dimorphism in both squirrel monkeys and cynomolgus monkeys occurred at an age of about 32 months. Data presented in this paper could be useful for comparative studies using primates under similar conditions.

  1. 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 between 5 and 2850 meters over sea level (mosl was of 6.39% (17/266. Most of them were adult males Saguinus leucopus, Saguinus oedipus, Saimiri sciureus and Aotus sp; corresponding to Matecaña, Santa Fe and Santacruz zoos, located between 1.001-2.000 mosl. The microfilarias species observed in this study are morphologically compatible with Dipetalonema perstans and Microfilaria bolivarensis, using direct drop technique, Woo, extended of central blood and capillary dyed with Giemsa and Knott, The most sensible technique was extended of central blood dyed with Giemsa. The statistical program used was Epi info 6.1, to determinate prevalence by sex, age, species, zoo, technique and altitude, with a significance level of (P = 0.05. The Saguinus leucopus showed high quantities of microfilaremias with sickness signs, so they were considered reservoirs and / or porter of the microfilarias.

  2. Allelic lineages of the ficolin genes (FCNs are passed from ancestral to descendant primates.

    Directory of Open Access Journals (Sweden)

    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.

  3. Impaired spatial information processing in aged monkeys with preserved recognition memory.

    Science.gov (United States)

    Rapp, P R; Kansky, M T; Roberts, J A

    1997-05-27

    Spatial information processing was examined in a non-human primate model of cognitive aging, using procedures formally similar to tasks designed for rats. The test apparatus was a large open field containing eight reward locations. Monkeys rapidly learned to visit each location once per trial, and probe manipulations confirmed that young animals navigated according to the distribution of cues surrounding the maze. In contrast, aged monkeys solved the task using a response sequencing strategy, independent of extramaze spatial information. Object recognition memory was normal in the aged group. The results reveal substantial correspondence in the cognitive effects of aging across rat and primate models, and they establish appropriate procedures for testing the long-standing proposal that the role of the hippocampus in normal spatial learning is similarly conserved.

  4. Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Darusman, H S; Call, J; Sajuthi, D

    2014-01-01

    We compared delayed response task performance in young, middle-aged, and old cynomolgus monkeys using three memory tests that have been used with non-human primates. Eighteen cynomolgus monkeys-6 young (4-9 years), 6 middle-aged (10-19 years), and 6 old (above 20 years)-were tested. In general......, the old monkeys scored significantly worse than did the animals in the two other age groups. Longer delays between stimulus presentation and response increased the performance differences between the old and younger monkeys. The old monkeys in particular showed signs of impaired visuo-spatial memory...

  5. Optical imaging of nociception in primary somatosensory cortex of non-human primates

    Institute of Scientific and Technical Information of China (English)

    Li-Min CHEN; Robert M. Friedman; Anna W. Roe

    2008-01-01

    While the activation of primary somatosensory (SI) cortex during pain perception is consistently reported in functional imaging studies on normal subjects and chronic pain patients, the specific roles of SI, particularly the subregions within SI, in the processing of sensory aspects of pain are still largely unknown. Using optical imaging of intrinsic signal (OIS) and single unit electrophysiology, we studied cortical activation patterns within SI cortex (among Brodmann areas 3a, 3b and 1) and signal amplitude changes to various intensities of non-nociceptive, thermal nociceptive and mechanical nociceptive stimulation of individual distal finerpads in anesthetized squirrel monkeys. We have demonstrated that areas 3a and 1 are preferentially involved in the processing of nociceptive information while areas 3b and 1 are preferentially activated in the processing of non-nociceptive (touch) information. Nociceptive activations of individual fingerpad were organized topographically suggesting that nociceptive topographic map exits in areas 3a and 1. Signal amplitude was enhanced to increasing intensity of mechanical nociceptive stimuli in areas 3a, 3b and 1. Within area 1, nociceptive response co-localizes with the non-nociceptive response. Therefore, we hypothesize that nocicepitve information is area-specifically represented within SI cortex, in which nociceptive inputs are preferentially represented in areas 3a and 1 while non-nociceptive inputs are preferentially represented in areas 3b and 1.

  6. 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.

  7. Microbial biofilms on the surface of intravaginal rings worn in non-human primates.

    Science.gov (United States)

    Gunawardana, Manjula; Moss, John A; Smith, Thomas J; Kennedy, Sean; Kopin, Etana; Nguyen, Cali; Malone, Amanda M; Rabe, Lorna; Schaudinn, Christoph; Webster, Paul; Srinivasan, Priya; Sweeney, Elizabeth D; Smith, James M; Baum, Marc M

    2011-06-01

    Millions of intravaginal rings (IVRs) are used by women worldwide for contraception and for the treatment of vaginal atrophy. These devices also are suitable for local and systemic sustained release drug delivery, notably for antiviral agents in human immunodeficiency virus pre-exposure prophylaxis. Despite the widespread use of IVRs, no studies have examined whether surface-attached bacterial biofilms develop in vivo, an important consideration when determining the safety of these devices. The present study used scanning electron microscopy, fluorescence in situ hybridization and confocal laser scanning microscopy to study biofilms that formed on the surface of IVRs worn for 28 days by six female pig-tailed macaques, an excellent model organism for the human vaginal microbiome. Four of the IVRs released the nucleotide analogue reverse transcriptase inhibitor tenofovir at a controlled rate and the remaining two were unmedicated. Large areas of the ring surfaces were covered with monolayers of epithelial cells. Two bacterial biofilm phenotypes were found to develop on these monolayers and both had a broad diversity of bacterial cells closely associated with the extracellular material. Phenotype I, the more common of the two, consisted of tightly packed bacterial mats approximately 5 µm in thickness. Phenotype II was much thicker, typically 40 µm, and had an open architecture containing interwoven networks of uniform fibres. There was no significant difference in biofilm thickness and appearance between medicated and unmedicated IVRs. These preliminary results suggest that bacterial biofilms could be common on intravaginal devices worn for extended periods of time.

  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 h

  9. 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.

  10. Experimental transmission of bovine spongiform encephalopathy (BSE) to cynomolgus macaques, a non-human primate.

    Science.gov (United States)

    Ono, Fumiko; Terao, Keiji; Tase, Naomi; Hiyaoka, Akio; Ohyama, Atsushi; Tezuka, Yukio; Wada, Naomi; Kurosawa, Asuka; Sato, Yuko; Tobiume, Minoru; Hagiwara, Ken'ichi; Yamakawa, Yoshio; Sata, Tetsutaro

    2011-01-01

    Bovine spongiform encephalopathy (BSE) was transmitted to three macaques by intracerebral inoculation of a brain homogenate from affected cattle detected in Japan. All monkeys developed abnormal behavioral signs, such as intermittent anorexia and hyperekplexia, around 24 months after inoculation. Neuronal symptoms, such as tremor, myoclonic jerking, and paralysis, appeared 27-44 months after inoculation. These symptoms worsened and total paralysis ensued within a year after onset. The disease duration was approximately 8-12 months. Both the incubation period and the duration of disease were shortened in the secondary transmission experiment to macaques. Heavy accumulation of disease-causing conformer(s) of prion protein (PrP(Sc)), with a similar glycoform profile to the PrP(Sc) contained in the inoculum, and severe spongiform changes in the histology of the brain, confirmed the successful transmission of BSE to monkeys. Florid plaques, a characteristic histological hallmark of variant Creutzfeldt-Jakob disease, were prominent in the cerebral cortex, in which a prion antigen was detected by immunohistochemistry (IHC). PrP(Sc) was mostly confined to the central nervous system, although small amounts of PrP(Sc) accumulated in the peripheral nerves of monkeys, as detected by Western blotting (WB). Neither IHC nor WB detected PrP(Sc) in the lymphatic organs/tissues, such as the tonsils, spleen, and appendix.

  11. Application of the Human Intestinal Tract Chip to the non-human primate gut microbiota

    NARCIS (Netherlands)

    Bello Gonzalez, T.D.G.; Passel, van M.W.J.; Tims, S.; Fuentes, S.; Vos, de W.M.; Smidt, H.; Belzer, C.

    2015-01-01

    The human intestinal microbiota is responsible for various health-related functions, and its diversity can be readily mapped with the 16S ribosomal RNA targeting Human Intestinal Tract (HIT) Chip. Here we characterise distal gut samples from chimpanzees, gorillas and marmosets, and compare them with

  12. Challenges in Mucosal HIV Vaccine Development: Lessons from Non-Human Primate Models

    OpenAIRE

    Iskra Tuero; Marjorie Robert-Guroff

    2014-01-01

    An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinic...

  13. Intrinsically motivated oculomotor exploration guided by uncertainty reduction and conditioned reinforcement in non-human primates.

    Science.gov (United States)

    Daddaoua, Nabil; Lopes, Manuel; Gottlieb, Jacqueline

    2016-02-03

    Intelligent animals have a high degree of curiosity--the intrinsic desire to know--but the mechanisms of curiosity are poorly understood. A key open question pertains to the internal valuation systems that drive curiosity. What are the cognitive and emotional factors that motivate animals to seek information when this is not reinforced by instrumental rewards? Using a novel oculomotor paradigm, combined with reinforcement learning (RL) simulations, we show that monkeys are intrinsically motivated to search for and look at reward-predictive cues, and that their intrinsic motivation is shaped by a desire to reduce uncertainty, a desire to obtain conditioned reinforcement from positive cues, and individual variations in decision strategy and the cognitive costs of acquiring information. The results suggest that free-viewing oculomotor behavior reveals cognitive and emotional factors underlying the curiosity driven sampling of information.

  14. Virulence of oral Fusobacterium nucleatum from humans and non-human primates in mice

    Directory of Open Access Journals (Sweden)

    Gaetti-Jardim Júnior Elerson

    2000-01-01

    Full Text Available The lethal action in Balb/c mice of 80 oral Fusobacterium nucleatum recovered from patients with adult periodontitis, healthy subjects or Cebus apella monkeys was studied. Mice were inoculated intraperitoneally with each bacterial inoculum of 5 x 10(8 CFU/ml. All the clinical isolates induced weight and coordinated movements loss. Pathological alterations in liver, CNS, heart, and kidney with inflammatory reactions or vascular congestion were observed. Of all the tested F. nucleatum isolates, 61.2% from periodontal patients, 57.1% from healthy subjects and 60% from monkeys, were capable of killing the mice in 48h. The clinical isolates were significantly more pathogenic than F. nucleatum ATCC 10953 or ATCC 25586. B. fragilis ATCC 23745 showed lethality against control mice. Our results suggest that LPS could be involved in lethal action against mice and it may play an important role in producing tissue damage or death of mice.

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

    OpenAIRE

    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...

  16. Preimplantation Development in Primates

    Institute of Scientific and Technical Information of China (English)

    H.B.Croxatto

    1992-01-01

    Essential phenomena involved in preimplamation development, notably cleavageand cell differentiation, are considered from the point of view of their relationships andtheir role in the formation of the blastocyst. The time course of egg transport from theovary to the site of implantation and the requirements.for in vitro development in pri-mate species for which there are some data are compared. Finally the ultrastructural features of human preimptantation development are analyzed, It is concluded that muchmore descriptive information of preimpltmtation development in primates needs to beaccrued to elaborate a comparative view.

  17. Prosocial primates: selfish and unselfish motivations.

    Science.gov (United States)

    de Waal, Frans B M; Suchak, Malini

    2010-09-12

    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.

  18. 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.

  19. 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.

  20. 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.

  1. A longitudinal analysis of the effects of age on the blood plasma metabolome in the common marmoset, Callithrix jacchus.

    Science.gov (United States)

    Hoffman, Jessica M; Tran, ViLinh; Wachtman, Lynn M; Green, Cara L; Jones, Dean P; Promislow, Daniel E L

    2016-04-01

    Primates tend to be long-lived for their size with humans being the longest lived of all primates. There are compelling reasons to understand the underlying age-related processes that shape human lifespan. But the very fact of our long lifespan that makes it so compelling, also makes it especially difficult to study. Thus, in studies of aging, researchers have turned to non-human primate models, including chimpanzees, baboons, and rhesus macaques. More recently, the common marmoset, Callithrix jacchus, has been recognized as a particularly valuable model in studies of aging, given its small size, ease of housing in captivity, and relatively short lifespan. However, little is known about the physiological changes that occur as marmosets age. To begin to fill in this gap, we utilized high sensitivity metabolomics to define the longitudinal biochemical changes associated with age in the common marmoset. We measured 2104 metabolites from blood plasma at three separate time points over a 17-month period, and we completed both a cross-sectional and longitudinal analysis of the metabolome. We discovered hundreds of metabolites associated with age and body weight in both male and female animals. Our longitudinal analysis identified age-associated metabolic pathways that were not found in our cross-sectional analysis. Pathways enriched for age-associated metabolites included tryptophan, nucleotide, and xenobiotic metabolism, suggesting these biochemical pathways might play an important role in the basic mechanisms of aging in primates. Moreover, we found that many metabolic pathways associated with age were sex specific. Our work illustrates the power of longitudinal approaches, even in a short time frame, to discover novel biochemical changes that occur with age.

  2. Referential alarm calling behaviour in New World primates

    Institute of Scientific and Technical Information of China (English)

    Cristiane C(A)SAR; Klaus ZUBERB(U)HLER

    2012-01-01

    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 Word 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 described in Old Word primates,we suggest

  3. Referential alarm calling behaviour in New World primates

    Directory of Open Access Journals (Sweden)

    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

  4. Good CoP, bad CoP? Interrogating the immune responses to primate lentiviral vaccines.

    Science.gov (United States)

    Klasse, Per Johan; Moore, John P

    2012-10-01

    Correlates of protection (CoPs) against infection by primate lentiviruses remain undefined. Modest protection against HIV-1 was observed in one human vaccine trial, whereas previous trials and vaccine-challenge experiments in non-human primates have yielded inconsistent but intriguing results. Although high levels of neutralizing antibodies are known to protect macaques from mucosal and intravenous viral challenges, antibody or other adaptive immune responses associated with protection might also be mere markers of innate immunity or susceptibility. Specific strategies for augmenting the design of both human trials and animal experiments could help to identify mechanistic correlates of protection and clarify the influences of confounding factors. Robust protection may, however, require the combined actions of immune responses and other host factors, thereby limiting what inferences can be drawn from statistical associations. Here, we discuss how to analyze immune protection against primate lentiviruses, and how host factors could influence both the elicitation and effectiveness of vaccine-induced responses.

  5. 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.

  6. Brains, genes, and primates.

    Science.gov (United States)

    Izpisua Belmonte, Juan Carlos; Callaway, Edward M; Caddick, Sarah J; Churchland, Patricia; 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

    2015-05-06

    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.

  7. 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

  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.

  9. 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.

  10. Detection of elevated antibody against calreticulin by ELISA in aged cynomolgus monkey plasma.

    Science.gov (United States)

    Higashino, Atsunori; Kageyama, Takashi; Kantha, Sachi Sri; Terao, Keiji

    2011-02-01

    Calreticulin (Crt) is a molecular chaperone ubiquitously present in the endoplasmic reticulum. In non-human primates, age-related occurrence of anti-Crt antibody has not been reported. We developed an ELISA assay for an anti-Crt antibody and determined the age-related increase in the levels of anti-Crt antibody in three groups of cynomolgus monkeys: juvenile (1.5 yr), young adults (5-10 yr) and aged adults (20-34 yr). Mean ± SD auto-antibody levels at 450 nm in juvenile, young adults and aged groups were 0.23 ± 0.18, 0.30 ± 0.28, and 0.55 ± 0.33, respectively. Statistically significant differences were noted in the autoantibody levels to Crt among the aged group and juvenile or young adults. This is the first report to demonstrate the expression of anti-Crt autoantibody in aged monkeys and indicates that cynomologous monkeys may serve as an appropriate nonhuman primate model for studies of age-related alteration of immune function in elderly humans. Though preliminary, this finding merits further investigation to determine the relationship between immunosenescence and expression of antibodies to Crt.

  11. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  12. Establishment of a Non-human Primate Campylobacter Disease Model for the Pre-clinical Evaluation of Campylobacter Vaccine Formulations

    Science.gov (United States)

    2005-07-25

    suspension medium. The suspension was adjusted and inoculated onto Brucella agar plates supplemented with 5% sheep blood, followed by incu- bation in...samples from each monkey were cultured twice (am and pm) daily. Fecal samples were cul- tured on Brucella agar plates supplemented with 5% sheep b z o p...wells in two-fold dilutions using 1% BSA in PBST and he plates were incubated for 3 h at 37 ◦C. After four further ashings, peroxidase labeled goat

  13. 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...

  14. 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

    2008-01-01

    Background 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 restricted diet (CR) on periodontitis in an animal model of periodontitis. Methods 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 plaque (PLI), probing pocket depth (PD), clinical attachment level (CAL), modified Gingival Index (GI) and bleeding on probing (BOP) were taken at baseline and 1, 2, and 3 months after ligature placement. Results Significant effects of CR were observed on the development of inflammation and the progression of periodontal destruction in this model. When compared to controls, CR resulted in a significant reduction in ligature induced GI (p<0.0001), BOP (p<0.0015), PD (p<0.0016), and CAL (p<0.0038). When viewed over time, periodontal destruction, as measured by CAL, progressed significantly more slowly in the CR animals than in the controls (p<0.001). Conclusions These clinical findings are consistent with available evidence that CR has anti-inflammatory effects. Moreover, these experimental findings are the first observations that CR dampens the inflammatory response and reduces active periodontal breakdown associated with an acute microbial challenge. PMID:18597600

  15. 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.

  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, behav

  17. Postexposure Protection Against Marburg Haemorrhagic Fever with Recombinant Vesicular Stomatitis Virus Vectors in Non-Human Primates: An Efficacy Assessment

    Science.gov (United States)

    2006-04-29

    virus (MARV). We aimed to test the effi cacy of a replication -competent vaccine based on attenuated recombinant vesicular stomatitis virus (rVSV...including vaccines based on recombinant adenoviruses12,13 and recombinant alphaviruses .8 We previously described the generation and assessment of a live...such as Marburg virus (MARV). We aimed to test the efficacy of a replication -competent vaccine based on attenuated recombinant vesicular stomatitis

  18. 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 a...

  19. Pharmacoligcal and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Non-Human Primate

    Science.gov (United States)

    2005-05-01

    determined using a cage-side clinical rating scale (CRS) based on 36 : 37 the Unified Parkinson’s Disease Rating Scale ( UPDRS ) and modified for the squirrel...Disease Rating Scale ( UPDRS ) and employs items related to motor behavior in the 10 11 squirrel monkey. The maximum total score is 24 points, which is

  20. Comparison of two I-123 labeled SPECT probes, for the dopamine transporter in non-human primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Gandelman, M.S.; Scanley, B.E.; Al-Tikrite, M.S. [Yale Univ., West Haven, CT (United States)] [and others

    1994-05-01

    A comparative SPECT evaluation of the regional uptake of 28-carboisopropoxy-3{beta}-(4-iodophenyl)tropane (IP-CIT) and 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ({beta}-CIT) was performed to assess the improved specificity of IP-CIT over {beta}-CIT for the dopamine (DE) transporter, as shown previously by in vitro studies (n=10), ranging from 7 to 10 hours with 6.9 to 15 mCi injected dose, were completed in 3 baboons. Peripheral metabolism of the two ligands were similar The SPECT images utilized ROIs over striatum (which reflect DA transporters), midbrain (previously shown for {beta}-CIT to reflect primarily serotonin transporters), and the occipital lobe (a region of non-specific uptake). The time to peak specific striatal uptake (striatal minus occipital activity) was similar for IP-CIT and {beta}-CIT (377{plus_minus}60 and 410{plus_minus}60 min, respectively); whereas midbrain peak activity occurred at a significantly earlier time for IP-CIT (21{plus_minus}4 min) as compared to {beta}-CIT (60{plus_minus}17 min). At time of peak specific striatal activity, striatal to occipital ratios were 2.7+0.6 for IP-CIT and 7.6{plus_minus}0.7 for {beta}-CIT, and at time of peak midbrain activity, midbrain to occipital ratios were 1.1{plus_minus}0.1 for IP-CIT, and 1.7{plus_minus}0.2 for {beta}-CIT. At peak specific striatal time, normalized regional uptake values ({mu}Ci/cc per {mu}Ci injected dose per g body mass) for the striatum were 4.9{plus_minus}1.1 IP-CIT and 5.2{plus_minus}0.7 {beta}-CIT, whereas for the occipital lobe normalized regional uptake values were 1.9{plus_minus}0.4 IP-CIT and 0.7{plus_minus}0.2 for {beta}-CIT. Similar regional kinetics in the striatum were observed, as both ligands demonstrate comparable peak striatal uptake and time to peak.

  1. Atypical L-type bovine spongiform encephalopathy (L-BSE) transmission to cynomolgus macaques, a non-human primate.

    Science.gov (United States)

    Ono, Fumiko; Tase, Naomi; Kurosawa, Asuka; Hiyaoka, Akio; Ohyama, Atsushi; Tezuka, Yukio; Wada, Naomi; Sato, Yuko; Tobiume, Minoru; Hagiwara, Ken'ichi; Yamakawa, Yoshio; Terao, Keiji; Sata, Tetsutaro

    2011-01-01

    A low molecular weight type of atypical bovine spongiform encephalopathy (L-BSE) was transmitted to two cynomolgus macaques by intracerebral inoculation of a brain homogenate of cattle with atypical BSE detected in Japan. They developed neurological signs and symptoms at 19 or 20 months post-inoculation and were euthanized 6 months after the onset of total paralysis. Both the incubation period and duration of the disease were shorter than those for experimental transmission of classical BSE (C-BSE) into macaques. Although the clinical manifestations, such as tremor, myoclonic jerking, and paralysis, were similar to those induced upon C-BSE transmission, no premonitory symptoms, such as hyperekplexia and depression, were evident. Most of the abnormal prion protein (PrP(Sc)) was confined to the tissues of the central nervous system, as determined by immunohistochemistry and Western blotting. The PrP(Sc) glycoform that accumulated in the monkey brain showed a similar profile to that of L-BSE and consistent with that in the cattle brain used as the inoculant. PrP(Sc) staining in the cerebral cortex showed a diffuse synaptic pattern by immunohistochemistry, whereas it accumulated as fine and coarse granules and/or small plaques in the cerebellar cortex and brain stem. Severe spongiosis spread widely in the cerebral cortex, whereas florid plaques, a hallmark of variant Creutzfeldt-Jakob disease in humans, were observed in macaques inoculated with C-BSE but not in those inoculated with L-BSE.

  2. Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates.

    Directory of Open Access Journals (Sweden)

    Fiona R Strouts

    2016-05-01

    Full Text Available The development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. Genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection.In this study, we measured early transcriptional responses in the peripheral blood of cynomolgus macaques following vaccination with a live, attenuated tetravalent dengue vaccine candidate, TDV, which is based on a DENV-2 backbone. Different doses and routes of vaccine administration were used, and viral load and neutralizing antibody titers were measured at different time-points following vaccination. All 30 vaccinated animals developed a neutralizing antibody response to each of the four dengue serotypes, and only 3 of these animals had detectable serum viral RNA after challenge with wild-type dengue virus (DENV, suggesting protection of vaccinated animals to DENV infection. The vaccine induced statistically significant changes in 595 gene transcripts on days 1, 3, 5 and 7 as compared with baseline and placebo-treated animals. Genes involved in the type I interferon (IFN response, including IFI44, DDX58, MX1 and OASL, exhibited the highest fold-change in transcript abundance, and this response was strongest following double dose and subcutaneous (versus intradermal vaccine administration. In addition, modules of genes involved in antigen presentation, dendritic cell activation, and T cell activation and signaling were enriched following vaccination. Increased abundance of gene transcripts related to T cell activation on day 5, and the type I IFN response on day 7, were significantly correlated with the development of high neutralizing antibody titers on day 30.These results suggest that early transcriptional responses may be predictive of development of adaptive immunity to TDV vaccination in cynomolgus macaques, and will inform studies of human responses to dengue vaccines.

  3. Emotion Evaluation and Response Slowing in a Non-Human Primate: New Directions for Cognitive Bias Measures of Animal Emotion?

    Directory of Open Access Journals (Sweden)

    Emily J. Bethell

    2016-01-01

    Full Text Available The cognitive bias model of animal welfare assessment is informed by studies with humans demonstrating that the interaction between emotion and cognition can be detected using laboratory tasks. A limitation of cognitive bias tasks is the amount of training required by animals prior to testing. A potential solution is to use biologically relevant stimuli that trigger innate emotional responses. Here; we develop a new method to assess emotion in rhesus macaques; informed by paradigms used with humans: emotional Stroop; visual cueing and; in particular; response slowing. In humans; performance on a simple cognitive task can become impaired when emotional distractor content is displayed. Importantly; responses become slower in anxious individuals in the presence of mild threat; a pattern not seen in non-anxious individuals; who are able to effectively process and disengage from the distractor. Here; we present a proof-of-concept study; demonstrating that rhesus macaques show slowing of responses in a simple touch-screen task when emotional content is introduced; but only when they had recently experienced a presumably stressful veterinary inspection. Our results indicate the presence of a subtle “cognitive freeze” response; the measurement of which may provide a means of identifying negative shifts in emotion in animals.

  4. Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates

    Science.gov (United States)

    Strouts, Fiona R.; Popper, Stephen J.; Partidos, Charalambos D.; Stinchcomb, Dan T.; Osorio, Jorge E.; Relman, David A.

    2016-01-01

    Background The development of a vaccine against dengue faces unique challenges, including the complexity of the immune responses to the four antigenically distinct serotypes. Genome-wide transcriptional profiling provides insight into the pathways and molecular features that underlie responses to immune system stimulation, and may facilitate predictions of immune protection. Methodology/Principal Findings In this study, we measured early transcriptional responses in the peripheral blood of cynomolgus macaques following vaccination with a live, attenuated tetravalent dengue vaccine candidate, TDV, which is based on a DENV-2 backbone. Different doses and routes of vaccine administration were used, and viral load and neutralizing antibody titers were measured at different time-points following vaccination. All 30 vaccinated animals developed a neutralizing antibody response to each of the four dengue serotypes, and only 3 of these animals had detectable serum viral RNA after challenge with wild-type dengue virus (DENV), suggesting protection of vaccinated animals to DENV infection. The vaccine induced statistically significant changes in 595 gene transcripts on days 1, 3, 5 and 7 as compared with baseline and placebo-treated animals. Genes involved in the type I interferon (IFN) response, including IFI44, DDX58, MX1 and OASL, exhibited the highest fold-change in transcript abundance, and this response was strongest following double dose and subcutaneous (versus intradermal) vaccine administration. In addition, modules of genes involved in antigen presentation, dendritic cell activation, and T cell activation and signaling were enriched following vaccination. Increased abundance of gene transcripts related to T cell activation on day 5, and the type I IFN response on day 7, were significantly correlated with the development of high neutralizing antibody titers on day 30. Conclusions/Significance These results suggest that early transcriptional responses may be predictive of development of adaptive immunity to TDV vaccination in cynomolgus macaques, and will inform studies of human responses to dengue vaccines. PMID:27214236

  5. Male food defence as a by-product of intersexual cooperation in a non-human primate

    Science.gov (United States)

    Arseneau-Robar, T. Jean M.; Müller, Eliane; Taucher, Anouk L.; van Schaik, Carel P.; Willems, Erik P.

    2016-01-01

    Males in a number of group-living species fight in intergroup conflicts to defend access to food resources, a seemingly paradoxical behaviour, given that this resource does not usually limit male fitness directly. We investigated the mechanism(s) driving apparent male food defence in wild vervet monkeys (Chlorocebus aethiops pygerythrus) by testing the effect that female resource access, and female audience size and activity had on the response of focal males during simulated intergroup encounters. Males do not appear to defend food to increase the reproductive success of female group members because their response was not influenced by the presence of provisioning boxes that only females could access. Female audience size was also unimportant, suggesting males do not participate in intergroup encounters to advertise their quality to potential mates. However, focal males almost always followed/supported female group members who initiated an approach towards simulated intruders, supporting that male participation largely functions to gain status as a cooperative group member, and that apparent male food defence in this species arises as a by-product of intersexual cooperation. Our study highlights that considering audience composition and activity can reveal the presence of social incentives and illuminate the evolutionary mechanism(s) promoting joint action in intergroup aggression. PMID:27775042

  6. Issues on combining human and non-human intelligence

    Science.gov (United States)

    Statler, Irving C.; Connors, Mary M.

    1991-01-01

    The purpose here is to call attention to some of the issues confronting the designer of a system that combines human and non-human intelligence. We do not know how to design a non-human intelligence in such a way that it will fit naturally into a human organization. The author's concern is that, without adequate understanding and consideration of the behavioral and psychological limitations and requirements of the human member(s) of the system, the introduction of artificial intelligence (AI) subsystems can exacerbate operational problems. We have seen that, when these technologies are not properly applied, an overall degradation of performance at the system level can occur. Only by understanding how human and automated systems work together can we be sure that the problems introduced by automation are not more serious than the problems solved.

  7. Identifying constraints in the evolution of primate societies.

    Science.gov (United States)

    Thierry, Bernard

    2013-05-19

    The evolutionary study of social systems in non-human primates has long been focused on ecological determinants. The predictive value of socio-ecological models remains quite low, however, in particular because such equilibrium models cannot integrate the course of history. The use of phylogenetic methods indicates that many patterns of primate societies have been conserved throughout evolutionary history. For example, the study of social relations in macaques revealed that their social systems are made of sets of correlated behavioural traits. Some macaque species are portrayed by marked social intolerance, a steep dominance gradient and strong nepotism, whereas others display a higher level of social tolerance, relaxed dominance and a weaker influence of kinship. Linkages between behavioural traits occur at different levels of organization, and act as constraints that limit evolutionary responses to external pressures. Whereas these constraints can exert strong stabilizing selection that opposes the potential changes required by the ecological environment, selective mechanisms may have the potential to switch the whole social system from one state to another by acting primarily on some key behavioural traits that could work as pacemakers.

  8. 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.

  9. Nuclear transfer in nonhuman primates.

    Science.gov (United States)

    Mitalipov, Shoukhrat M; Wolf, Don P

    2006-01-01

    The nonhuman primate is a highly relevant model for the study of human diseases, and currently there is a significant need for populations of animals with specific genotypes that can not be satisfied by the capture of animals from the wild or by conventional breeding. There is an even greater need for genetically identical animals in vaccine development or tissue transplantation research, where immune system function is under study. Efficient somatic cell nuclear transfer (SCNT) procedures could provide a source for genetically identical nonhuman primates for biomedical research. SCNT offers the possibility of cloning animals using cultured cells and potentially provides an alternative approach for the genetic modification of primates. The opportunity to introduce precise genetic modifications into cultured cells by gene targeting procedures, and then use these cells as nuclear donors in SCNT, has potential application in the production of loss-of-function monkey models of human diseases. We were initially successful in producing monkeys by NT using embryonic blastomeres as the source of donor nuclei and have repeated that success. However, when somatic cells are used as nuclear donor cells, the developmental potential of monkey SCNT embryos is limited, and somatic cell cloning has not yet been accomplished in primates. High rates of in vitro development to blastocysts, comparable with in vitro fertilization controls, and successful production of rhesus monkeys by NT from embryonic blastomeres suggests that basic cloning procedures, including enucleation, fusion, and activation, are consistent with the production of viable embryos. Although modifications or additional steps in SCNT are clearly warranted, the basic procedures will likely be similar to those extant for embryonic cell NT. In this chapter, we describe detailed protocols for rhesus macaque embryonic cell NT, including oocyte and embryo production, micromanipulation, and embryo transfer in nonhuman

  10. Alopecia: possible causes and treatments, particularly in captive nonhuman primates.

    Science.gov (United States)

    Novak, Melinda A; Meyer, Jerrold S

    2009-02-01

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

  11. The fourth dimension of tool use: temporally enduring artefacts aid primates learning to use tools.

    Science.gov (United States)

    Fragaszy, D M; Biro, D; Eshchar, Y; Humle, T; Izar, P; Resende, B; Visalberghi, E

    2013-11-19

    All investigated cases of habitual tool use in wild chimpanzees and capuchin monkeys include youngsters encountering durable artefacts, most often in a supportive social context. We propose that enduring artefacts associated with tool use, such as previously used tools, partly processed food items and residual material from previous activity, aid non-human primates to learn to use tools, and to develop expertise in their use, thus contributing to traditional technologies in non-humans. Therefore, social contributions to tool use can be considered as situated in the three dimensions of Euclidean space, and in the fourth dimension of time. This notion expands the contribution of social context to learning a skill beyond the immediate presence of a model nearby. We provide examples supporting this hypothesis from wild bearded capuchin monkeys and chimpanzees, and suggest avenues for future research.

  12. Detection of arboviruses of public health interest in free-living New World primates (Sapajus spp.; Alouatta caraya captured in Mato Grosso do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. El primatólogo y la filósofa: tres ideas que comparten Frans de Waal y Mary Midgley

    OpenAIRE

    2014-01-01

    This paper explains the following three similarities between the thought of primatologist Frans de Waal and philosopher Mary Midgley: (a) rejection of Hobbesian contract theory, (b) emphasis on altruism in both the human and non-human animal realms as a basis for human ethics and (c) defense of anthropomorphism in observations of feelings and behavior in non-human animals. Este ensayo explica las siguientes tres semejanzas entre el pensamiento del primatólogo Frans de Waal y la filósofa Ma...

  15. Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus.

    Directory of Open Access Journals (Sweden)

    Julia Marchal

    Full Text Available The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV, a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day(-1·kg(-1. Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT and the homeostasis model assessment of insulin resistance (HOMA-IR index evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR index, with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic

  16. The primate hippocampus: ontogeny, early insult and memory.

    Science.gov (United States)

    Bachevalier, Jocelyne; Vargha-Khadem, Faraneh

    2005-04-01

    Recent evidence suggests that in primates, as in rodents, the hippocampus shows a developmental continuum that affects memory abilities from infancy to adulthood. In primates relatively few hippocampal-dependent abilities (e.g. some aspects of recognition memory) are present in early infancy, whereas others (e.g. relational memory) begin to show adult-like characteristics around 2 years of age in monkeys and 5-7 years in humans. Profound and persistent memory loss resulting from insult to the hippocampus in infancy becomes evident in everyday behavior only later in childhood. This pattern of results suggests a maturational gradient within the medial temporal lobe memory system, with most abilities crucially dependent upon the hippocampus emerging in later stages of development, supporting a model of hierarchical organization of memory within the medial temporal lobe.

  17. The Special Column of Primate Behavior

    Institute of Scientific and Technical Information of China (English)

    Baoguo LI; Guest Editor

    2010-01-01

    @@ It is a long-term policy to publish SPECIAL COLUMNs in Current Zoology, and I am delighted that the journal is publishing this special colunm devoted to the topic of Primate Behavior. The eight papers in this seetion present significant new data and synthesize these findings with existing information on sexual selection of human-being and behaviors of living primates.

  18. Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

    Science.gov (United States)

    Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

    1996-01-01

    Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human

  19. Comparative expression analysis of the phosphocreatine circuit in extant primates: Implications for human brain evolution.

    Science.gov (United States)

    Pfefferle, Adam D; Warner, Lisa R; Wang, Catrina W; Nielsen, William J; Babbitt, Courtney C; Fedrigo, Olivier; Wray, Gregory A

    2011-02-01

    While the hominid fossil record clearly shows that brain size has rapidly expanded over the last ~2.5 M.yr. the forces driving this change remain unclear. One popular hypothesis proposes that metabolic adaptations in response to dietary shifts supported greater encephalization in humans. An increase in meat consumption distinguishes the human diet from that of other great apes. Creatine, an essential metabolite for energy homeostasis in muscle and brain tissue, is abundant in meat and was likely ingested in higher quantities during human origins. Five phosphocreatine circuit proteins help regulate creatine utilization within energy demanding cells. We compared the expression of all five phosphocreatine circuit genes in cerebral cortex, cerebellum, and skeletal muscle tissue for humans, chimpanzees, and rhesus macaques. Strikingly, SLC6A8 and CKB transcript levels are higher in the human brain, which should increase energy availability and turnover compared to non-human primates. Combined with other well-documented differences between humans and non-human primates, this allocation of energy to the cerebral cortex and cerebellum may be important in supporting the increased metabolic demands of the human brain.

  20. Properties of virion transactivator proteins encoded by primate cytomegaloviruses

    Directory of Open Access Journals (Sweden)

    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

  1. 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

  2. Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Kazuya Kitamura

    Full Text Available Many therapeutic interventions for spinal cord injury (SCI using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF, which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI.

  3. In utero recombinant adeno-associated virus gene transfer in mice, rats, and primates

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    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.

  4. Good CoP, bad CoP? Interrogating the immune responses to primate lentiviral vaccines

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    Klasse Per

    2012-10-01

    Full Text Available Abstract Correlates of protection (CoPs against infection by primate lentiviruses remain undefined. Modest protection against HIV-1 was observed in one human vaccine trial, whereas previous trials and vaccine-challenge experiments in non-human primates have yielded inconsistent but intriguing results. Although high levels of neutralizing antibodies are known to protect macaques from mucosal and intravenous viral challenges, antibody or other adaptive immune responses associated with protection might also be mere markers of innate immunity or susceptibility. Specific strategies for augmenting the design of both human trials and animal experiments could help to identify mechanistic correlates of protection and clarify the influences of confounding factors. Robust protection may, however, require the combined actions of immune responses and other host factors, thereby limiting what inferences can be drawn from statistical associations. Here, we discuss how to analyze immune protection against primate lentiviruses, and how host factors could influence both the elicitation and effectiveness of vaccine-induced responses.

  5. Deep Hierarchies in the Primate Visual Cortex

    DEFF Research Database (Denmark)

    Krüger, Norbert; Jannsen, Per; Kalkan, S.

    2013-01-01

    of the processing hierarchies present in the primate visual system considering recent discoveries in neurophysiology. The hierarchal processing in the primate visual system is characterized by a sequence of different levels of processing (in the order of ten) that constitute a deep hierarchy in contrast to the flat...... vision architectures predominantly used in today's mainstream computer vision. We hope that the functional description of the deep hierarchies realized in the primate visual system provides valuable insights for the design of computer vision algorithms, fostering increasingly productive interaction...

  6. Primates in 21st century ecosystems: does primate conservation promote ecosystem conservation?

    Science.gov (United States)

    Norconk, Marilyn A; Boinski, Sue; Forget, Pierre-Michel

    2011-01-01

    Contributors to this issue of the American Journal of Primatology were among the participants in an invited symposium at the 2008 Association for Tropical Biology and Conservation meeting in Paramaribo, Suriname. They were asked to assess how essential primates are to tropical ecosystems and, given their research interests, discuss how primate research contributes to the broader understanding about how ecosystems function. This introduction to the issue is divided into three parts: a review of the roles that nonhuman primates play in tropical ecosystems; the implementation of large-scale landscape methods used to identify primate densities; and concerns about the increasingly porous boundaries between humans, nonhuman primates, and pathogens. Although 20th century primate research created a rich database on individual species, including both theoretical and descriptive approaches, the dual effects of high human population densities and widespread habitat destruction should warn us that creative, interdisciplinary and human-related research is needed to solve 21st century problems.

  7. Animal models of age related macular degeneration.

    Science.gov (United States)

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  8. The primate vaginal microbiome: comparative context and implications for human health and disease.

    Science.gov (United States)

    Stumpf, Rebecca M; Wilson, Brenda A; Rivera, Angel; Yildirim, Suleyman; Yeoman, Carl J; Polk, John D; White, Bryan A; Leigh, Steven R

    2013-12-01

    The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host-microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive-age humans show distinct microbial communities, generally dominated by Lactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host-microbe coevolution and adaptation.

  9. Nodule worm infection in humans and wild primates in Uganda: cryptic species in a newly identified region of human transmission.

    Directory of Open Access Journals (Sweden)

    Ria R Ghai

    Full Text Available INTRODUCTION: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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

  10. Female and male life tables for seven wild primate species.

    Science.gov (United States)

    Bronikowski, Anne M; Cords, Marina; Alberts, Susan C; Altmann, Jeanne; Brockman, Diane K; Fedigan, Linda M; Pusey, Anne; Stoinski, Tara; Strier, Karen B; Morris, William F

    2016-03-01

    We provide male and female census count data, age-specific survivorship, and female age-specific fertility estimates for populations of seven wild primates that have been continuously monitored for at least 29 years: sifaka (Propithecus verreauxi) in Madagascar; muriqui (Brachyteles hypoxanthus) in Brazil; capuchin (Cebus capucinus) in Costa Rica; baboon (Papio cynocephalus) and blue monkey (Cercopithecus mitis) in Kenya; chimpanzee (Pan troglodytes) in Tanzania; and gorilla (Gorilla beringei) in Rwanda. Using one-year age-class intervals, we computed point estimates of age-specific survival for both sexes. In all species, our survival estimates for the dispersing sex are affected by heavy censoring. We also calculated reproductive value, life expectancy, and mortality hazards for females. We used bootstrapping to place confidence intervals on life-table summary metrics (R0, the net reproductive rate; λ, the population growth rate; and G, the generation time). These data have high potential for reuse; they derive from continuous population monitoring of long-lived organisms and will be invaluable for addressing questions about comparative demography, primate conservation and human evolution.

  11. Mitochondrial gene replacement in primate offspring and embryonic stem cells.

    Science.gov (United States)

    Tachibana, Masahito; Sparman, Michelle; Sritanaudomchai, Hathaitip; Ma, Hong; Clepper, Lisa; Woodward, Joy; Li, Ying; Ramsey, Cathy; Kolotushkina, Olena; Mitalipov, Shoukhrat

    2009-09-17

    Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.

  12. Functional and cellular adaptation to weightlessness in primates

    Science.gov (United States)

    Bodine-Fowler, Sue C.; Pierotti, David J.; Talmadge, Robert J.

    1995-01-01

    Considerable data has been collected on the response of hindlimb muscles to unloading due to both spaceflight and hindlimb suspension. One generalized response to a reduction in load is muscle fiber atrophy, although not all muscles respond the same. Our understanding of how muscles respond to microgravity, however, has come primarily from the examination of hindlimb muscles in the unrestrained rate in space. The non-human primate spaceflight paradigm differs considerably from the rodent paradigm in that the monkeys are restrained, usually in a sitting position, while in space. Recently, we examined the effects of microgravity on muscles of the Rhesus monkey by taking biopsies of selected hindlimb muscles prior to and following spaceflights of 14 and 12 day durations (Cosmos 2044 and 2229). Our results revealed that the monkey's response to microgravity differs from that of the rat. The apparent differences in the atrophic response of the hindlimb muscles of the monkey and rat to spaceflight may be attributed to the following: (1) a species difference; (2) a difference in the manner in which the animals were maintained during the flight (i.e., chair restraint or 'free-floating'); and/or (3) an ability of the monkeys to counteract the effects of spaceflight with resistive exercise.

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

    Science.gov (United States)

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

    2016-08-30

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

  14. Biokinetics of Plutonium in Nonhuman Primates.

    Science.gov (United States)

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

    2016-10-01

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

  15. 42 CFR 71.53 - Nonhuman primates.

    Science.gov (United States)

    2010-10-01

    ... for use in breeding colonies is also permitted provided that all offspring will be used only for... cause(s) of deaths. If any primates in the shipment are sold or otherwise distributed within 90...

  16. Relationships between body weight, fasting blood glucose concentration, sex and age in tree shrews (Tupaia belangeri chinensis).

    Science.gov (United States)

    Wu, X; Chang, Q; Zhang, Y; Zou, X; Chen, L; Zhang, L; Lv, L; Liang, B

    2013-12-01

    The tree shrew (Tupaia belangeri chinensis) is a squirrel-like lower primate or a close relative of primates, commonly used as an animal model in biomedical research. Despite more than three decades of usage in research, the clear relationships between body weight, fasting blood glucose concentration, sex and age among tree shrews remain unclear. Based on an investigation of 992 tree shrews (454 males and 538 females) aged between 4 months and 4 years old, we found that male tree shrews have significantly higher body weight and fasting blood glucose concentration than female tree shrews (p < 0.001). The concentration of fasting blood glucose slightly increased with body weight in males (r = 0.152, p < 0.001). Meanwhile, in females, the body weight, concentration of fasting blood glucose and waist circumference positively increased with age (p < 0.001). Additionally, 17 tree shrews with Lee index [body weight (g)*0.33*1000/body length (cm)] above 290 had significantly higher body weight, waist circumference and glycated haemoglobin A1c (HbA1c) than non-obese tree shrews with a Lee index score below 290 (p < 0.001). Interestingly, 6 of 992 tree shrews (three males and three females, 2-4 years old) displayed impaired plasma triglycerides, HbA1c, low-density lipoprotein and oral glucose tolerance test, suggestive of the early symptoms of metabolic syndrome. This study provides the first clear relationships between body weight, fasting blood glucose concentration, sex and age in tree shrews, further improving our understanding of this relationship in metabolic syndrome (MetS). Given the similarity of tree shrews to humans and non-human primates, this finding supports their potential use as an animal model in the research of MetS.

  17. Colombian and Peruvian Primate Censusing Studies,

    Science.gov (United States)

    1975-06-01

    34PG ’AMR 0719) from the Pan American Health Organization (PAHO) and funds from the Instituto de Desarrollo de los Recursos Naturales Renovables...04 FEB. 7?5 En Iia. " Discusion de la cirta convenio para el Desorrolla do un Proyocto do investi-&iciones Piologicas solbre Primates no humanos onl...adecuadas para garantizar la utilizacion y la pe.-petuidad de especies de primates no humanos . 2- Realizar investigaciones de campo para determinar: el estado

  18. Nonhuman primate models of polycystic ovary syndrome

    OpenAIRE

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

    2013-01-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. L...

  19. Effects of Early IL-17A Neutralization on Disease Induction in a Primate Model of Experimental Autoimmune Encephalomyelitis

    OpenAIRE

    Kap, Yolanda S.; Jagessar, S. Anwar; Driel, Nikki; Blezer, Erwin; Bauer, Jan; van Meurs, Marjan; Smith, Paul; Laman, Jon D.; Bert A. ‘t Hart

    2010-01-01

    We report on the effect of antibody-mediated neutralization of interleukin (IL)-17A in a non-human primate experimental autoimmune encephalomyelitis (EAE) model induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We tested a human-anti-human IL-17A-antibody in two doses (3 and 30 mg/kg) against placebo (PBS). The treatment was started 1 day before EAE induction and continued throughout the experiment. Although all monkeys developed clinically evident EAE, the onset of ...

  20. Prevalence of Entamoeba species in captive primates in zoological gardens in the UK

    Directory of Open Access Journals (Sweden)

    Carl S. Regan

    2014-07-01

    Full Text Available The aim of this study was to determine the prevalence of amoebic infection in non-human primates (NHPs from six Zoological gardens in the United Kingdom. Initially, 126 faecal samples were collected from 37 individually identified NHPs at Twycross Zoo, UK, and were subjected to microscopic examination. A subsequent, nationwide experiment included 350 faecal samples from 89 individually identified NHPs and 73 unidentified NHPs from a number of UK captive wildlife facilities: Twycross Zoo (n = 60, Colchester Zoo (n = 3, Edinburgh Zoo (n = 6, Port Lympne Wild Animal Park (n = 58, Howletts Wild Animal Park (n = 31, and Cotswold Wildlife Park (n = 4. Samples were examined by PCR and sequencing using four specific primer sets designed to differentiate between the pathogenic E. histolytica, the non-pathogenic E. dispar, and non-pathogenic uninucleate cyst-producing Entamoeba species. In the first experiment, Entamoeba was detected in 30 primates (81.1%. Six (16.2% primates were infected with E. histolytica species complex. The highest carriage of Entamoeba species was found in Old World Colobinae primates. In the nationwide experiment, molecular analysis of faecal samples revealed notable rates of Entamoeba infection (101 samples, 28.9%, including one sample infected with E. histolytica, 14 samples with E. dispar, and 86 samples with uninucleated-cyst producing Entamoeba species. Sequences of positive uninucleated-cyst producing Entamoeba samples from Twycross Zoo clustered with the E. polecki reference sequences ST4 reported in Homo sapiens, and are widely separated from other Entamoeba species. These findings suggest a low prevalence of the pathogenic Entamoeba infection, but notable prevalence of non-pathogenic E. polecki infection in NHPs in the UK.

  1. Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

    Science.gov (United States)

    Croker, Sarah L; Reed, Warren; Donlon, Denise

    2016-03-01

    The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone

  2. Age-related neurochemical changes in the rhesus macaque inferior colliculus.

    Directory of Open Access Journals (Sweden)

    James eEngle

    2014-04-01

    Full Text Available Age-related hearing loss (ARHL is marked by audiometric hearing deficits that propagate along the auditory pathway. Neurochemical changes as a function of aging have also been identified in neurons along the auditory pathway in both rodents and carnivores, however, very little is known about how these neurochemicals change in the non-human primate. To examine how these compensatory neurochemical changes relate to normal aging and audiometric sensitivity along the auditory pathway, we collected auditory brainstem responses (ABRs and brain specimens from seven rhesus monkeys spanning in age from 15 to 35 years old, and examined the relationship between click evoked ABR thresholds and the ABR evoked pure tone average and changes in the number of parvalbumin and NADPH-diaphorase positive cells in the auditory midbrain. We found that the number of parvalbumin positive cells in the central nucleus and the surrounding cortex regions of the inferior colliculus were strongly correlated with advancing age and ABR pure tone average. We also found that the numbers of NADPHd positive cells in these same regions were not associated with normal aging or changes in the ABR thresholds. These findings suggest that the auditory midbrain undergoes an up-regulation of parvalbumin expressing neurons with aging that is related to changes in the processing of frequencies across the audiometric range.

  3. Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

    Directory of Open Access Journals (Sweden)

    Hirai Hirohisa

    2010-07-01

    Full Text Available Abstract Background Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%, suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed. Results Phylogenetic analysis of this low p-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (i.e., Old World monkeys and hominoids. A KALY-converted KALX allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low p-distance region is located in a LINE element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near VCX, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes. Conclusion Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the

  4. Episodic evolution of prolactin gene in primates

    Institute of Scientific and Technical Information of China (English)

    LI Ying; DUAN Ziyuan; JIA Lu; ZHANG Yaping

    2005-01-01

    In the present study, we obtained exon 2―5 of prolactin (PRL) gene from four primate species by PCR and sequencing. Adding other genes available in GenBank, we calculate amino acid substitution rates for prolactin gene in primate. Comparison of nonsynonymous substitution rate to synonymous substitution rate ratios shows no evidence of positive selection for any lineage of primate prolactin gene. According to this and the facts that (I) no sites under positive selection are inferred by using maximum-likelihood method; (ii) among 32 amino acid replacement that occurred along the rapid evolutionary phase, only two are included in the 40 functionally important residues, indicating that amino acid replacement tends to occur in those functionally unimportant residues; (iii) partial of prolactin function is replaced by placental lactogen in primate at the rapid evolutionary phase of prolactin gene, we thus deem that it is relaxation of purifying selection to some extent rather than positive selection that enforces the rapid evolution of primate prolactin gene.

  5. Operant nociception in nonhuman primates.

    Science.gov (United States)

    Kangas, Brian D; Bergman, Jack

    2014-09-01

    The effective management of pain is a longstanding public health concern. Morphine-like opioids have long been front-line analgesics, but produce undesirable side effects that can limit their application. Slow progress in the introduction of novel improved medications for pain management over the last 5 decades has prompted a call for innovative translational research, including new preclinical assays. Most current in vivo procedures (eg, tail flick, hot plate, warm water tail withdrawal) assay the effects of nociceptive stimuli on simple spinal reflexes or unconditioned behavioral reactions. However, clinical treatment goals may include the restoration of previous behavioral activities, which can be limited by medication-related side effects that are not measured in such procedures. The present studies describe an apparatus and procedure to study the disruptive effects of nociceptive stimuli on voluntary behavior in nonhuman primates, and the ability of drugs to restore such behavior through their analgesic actions. Squirrel monkeys were trained to pull a cylindrical thermode for access to a highly palatable food. Next, sessions were conducted in which the temperature of the thermode was increased stepwise until responding stopped, permitting the determination of stable nociceptive thresholds. Tests revealed that several opioid analgesics, but not d-amphetamine or Δ(9)-THC, produced dose-related increases in threshold that were antagonist sensitive and efficacy dependent, consistent with their effects using traditional measures of antinociception. Unlike traditional reflex-based measures, however, the results also permitted the concurrent evaluation of response disruption, providing an index with which to characterize the behavioral selectivity of antinociceptive drugs.

  6. Convergent evolution in primates and an insectivore

    Energy Technology Data Exchange (ETDEWEB)

    Boffelli, Dario; Cheng, Jan-Fang; Rubin, Edward M.

    2003-04-16

    The cardiovascular risk factor apolipoprotein(a) (apo(a)) has a puzzling distribution among mammals, its presence being limited to a subset of primates and a member of the insectivore lineage, the hedgehog. To explore the evolutionary history of apo(a), we performed extensive genomic sequence comparisons of multiple species with and without an apo(a) gene product, such as human, baboon, hedgehog, lemurand mouse. This analysis indicated that apo(a) arose independently in a subset of primates, including baboon and human, and an insectivore, the hedgehog, and was not simply lost by species lacking it. The similar structural domains shared by the hedgehog and primate apo(a) indicate that they were formed by a unique molecular mechanism involving the convergent evolution of paralogous genes in these distantspecies.

  7. Progress with nonhuman primate embryonic stem cells.

    Science.gov (United States)

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

    2004-12-01

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

  8. Sexual Selection and the Evolution of Brain Size in Primates

    OpenAIRE

    2006-01-01

    Reproductive competition among males has long been considered a powerful force in the evolution of primates. The evolution of brain size and complexity in the Order Primates has been widely regarded as the hallmark of primate evolutionary history. Despite their importance to our understanding of primate evolution, the relationship between sexual selection and the evolutionary development of brain size is not well studied. The present research examines the evolutionary relationship between bra...

  9. What’s in a Name?—Consequences of Naming Non-Human Animals

    Directory of Open Access Journals (Sweden)

    Sune Borkfelt

    2011-01-01

    Full Text Available The act of naming is among the most basic actions of language. Indeed, it is naming something that enables us to communicate about it in specific terms, whether the object named is human or non-human, animate or inanimate. However, naming is not as uncomplicated as we may usually think and names have consequences for the way we think about animals (human and non-human, peoples, species, places, things etc. Through a blend of history, philosophy and representational theory—and using examples from, among other things, the Bible, Martin Luther, colonialism/imperialism and contemporary ways of keeping and regarding non-human animals—this paper attempts to trace the importance of (both specific and generic naming to our relationships with the non-human. It explores this topic from the naming of the animals in Genesis to the names given and used by scientists, keepers of companion animals, media etc. in our societies today, and asks the question of what the consequences of naming non-human animals are for us, for the beings named and for the power relations between our species and the non-human species and individuals we name.

  10. Learning about primates' learning, language, and cognition

    Science.gov (United States)

    Rumbaugh, Duane M.

    1992-01-01

    Results are presented of many years of research on the methods of teaching primates the language and cognitive skills which were long considered to be unteachable to particular species of primates. It was found that chimpanzee subjects could not only learn a number of 'stock sentences' but to use them in variations and several combinations for the purpose of solving various problems. Apes placed in different rooms could be taught to communicate via computer, and collaborate with each other on doing specific tasks. Contrary to expectations, young rhesus monkeys proved to be able to learn as much as the chimpanzee species.

  11. Promiscuity and the primate immune system.

    Science.gov (United States)

    Nunn, C L; Gittleman, J L; Antonovics, J

    2000-11-10

    The behavioral and ecological factors involved in immune system evolution remain poorly explored. We present a phylogenetic analysis of white blood cell counts in primates to test three hypotheses related to disease risk: increases in risk are expected with group size or population density, exposure to soil-borne pathogens, and mating promiscuity. White blood cell counts were significantly greater in species where females have more mating partners, indicating that the risk of sexually transmitted disease is likely to be a major factor leading to systematic differences in the primate immune system.

  12. Primate theory of mind: a state of the art review

    DEFF Research Database (Denmark)

    Byrnit, Jill

    2006-01-01

    Såvel mennesket som andre primater have store hjerner med store hjernebarker. Det er blevet foreslået, at primaters store hjerner skyldes de komplekse sociale krav, der kommer af at skulle leve i store grupper. Inden for de sidste 40 år er der blevet lavet meget forskning inden for primaters soci...

  13. Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function

    Directory of Open Access Journals (Sweden)

    Zhang Rui

    2011-10-01

    Full Text Available Abstract Background Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence. Results We studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species. Conclusions RHOXF2 is a fast-evolving homeobox gene in primates. The rapid

  14. Comparative primate neuroimaging: insights into human brain evolution.

    Science.gov (United States)

    Rilling, James K

    2014-01-01

    Comparative neuroimaging can identify unique features of the human brain and teach us about human brain evolution. Comparisons with chimpanzees, our closest living primate relative, are critical in this endeavor. Structural magnetic resonance imaging (MRI) has been used to compare brain size development, brain structure proportions and brain aging. Positron emission tomography (PET) imaging has been used to compare resting brain glucose metabolism. Functional MRI (fMRI) has been used to compare auditory and visual system pathways, as well as resting-state networks of connectivity. Finally, diffusion-weighted imaging (DWI) has been used to compare structural connectivity. Collectively, these methods have revealed human brain specializations with respect to development, cortical organization, connectivity, and aging. These findings inform our knowledge of the evolutionary changes responsible for the special features of the modern human mind.

  15. Detection of Plasmodium in faeces of the New World primate Alouatta clamitans.

    Science.gov (United States)

    Assis, Gabriela Maíra Pereira de; Alvarenga, Denise Anete Madureira de; Costa, Daniela Camargos; Souza, Júlio César de; Hirano, Zelinda Maria Braga; Kano, Flora Satiko; Sousa, Taís Nóbrega de; Brito, Cristiana Ferreira Alves de

    2016-09-01

    Plasmodium falciparum and Plasmodium vivax have evolved with host switches between non-human primates (NHPs) and humans. Studies on the infection dynamics of Plasmodium species in NHPs will improve our understanding of the evolution of these parasites; however, such studies are hampered by the difficulty of handling animals in the field. The aim of this study was to detect genomic DNA of Plasmodium species from the faeces of New World monkeys. Faecal samples from 23 Alouatta clamitans from the Centre for Biological Research of Indaial (Santa Catarina, Brazil) were collected. Extracted DNA from faecal samples was used for molecular diagnosis of malaria by nested polymerase chain reaction. One natural infection with Plasmodium simium was identified by amplification of DNA extracted from the faeces of A. clamitans. Extracted DNA from a captive NHP was also used for parasite genotyping. The detection limit of the technique was evaluated in vitro using an artificial mixture of cultured P. falciparum in NHP faeces and determined to be 6.5 parasites/µL. Faecal samples of New World primates can be used to detect malaria infections in field surveys and also to monitor the genetic variability of parasites and dynamics of infection.

  16. On parsing the neural code in the prefrontal cortex of primates using principal dynamic modes.

    Science.gov (United States)

    Marmarelis, V Z; Shin, D C; Song, D; Hampson, R E; Deadwyler, S A; Berger, T W

    2014-06-01

    Nonlinear modeling of multi-input multi-output (MIMO) neuronal systems using Principal Dynamic Modes (PDMs) provides a novel method for analyzing the functional connectivity between neuronal groups. This paper presents the PDM-based modeling methodology and initial results from actual multi-unit recordings in the prefrontal cortex of non-human primates. We used the PDMs to analyze the dynamic transformations of spike train activity from Layer 2 (input) to Layer 5 (output) of the prefrontal cortex in primates performing a Delayed-Match-to-Sample task. The PDM-based models reduce the complexity of representing large-scale neural MIMO systems that involve large numbers of neurons, and also offer the prospect of improved biological/physiological interpretation of the obtained models. PDM analysis of neuronal connectivity in this system revealed "input-output channels of communication" corresponding to specific bands of neural rhythms that quantify the relative importance of these frequency-specific PDMs across a variety of different tasks. We found that behavioral performance during the Delayed-Match-to-Sample task (correct vs. incorrect outcome) was associated with differential activation of frequency-specific PDMs in the prefrontal cortex.

  17. Abundant human DNA contamination identified in non-primate genome databases.

    Directory of Open Access Journals (Sweden)

    Mark S Longo

    Full Text Available During routine screens of the NCBI databases using human repetitive elements we discovered an unlikely level of nucleotide identity across a broad range of phyla. To ascertain whether databases containing DNA sequences, genome assemblies and trace archive reads were contaminated with human sequences, we performed an in depth search for sequences of human origin in non-human species. Using a primate specific SINE, AluY, we screened 2,749 non-primate public databases from NCBI, Ensembl, JGI, and UCSC and have found 492 to be contaminated with human sequence. These represent species ranging from bacteria (B. cereus to plants (Z. mays to fish (D. rerio with examples found from most phyla. The identification of such extensive contamination of human sequence across databases and sequence types warrants caution among the sequencing community in future sequencing efforts, such as human re-sequencing. We discuss issues this may raise as well as present data that gives insight as to how this may be occurring.

  18. Compatibility counts: MHC-associated mate choice in a wild promiscuous primate.

    Science.gov (United States)

    Schwensow, Nina; Eberle, Manfred; Sommer, Simone

    2008-03-07

    The mechanisms and temporal aspects of mate choice according to genetic constitution are still puzzling. Recent studies indicate that fitness is positively related to diversity in immune genes (MHC). Both sexes should therefore choose mates of high genetic quality and/or compatibility. However, studies addressing the role of MHC diversity in pre- and post-copulatory mate choice decisions in wild-living animals are few. We investigated the impact of MHC constitution and of neutral microsatellite variability on pre- and post-copulatory mate choice in both sexes in a wild population of a promiscuous primate, the grey mouse lemur (Microcebus murinus). There was no support for pre-copulatory male or female mate choice, but our data indicate post-copulatory mate choice that is associated with genetic constitution. Fathers had a higher number of MHC supertypes different from those of the mother than randomly assigned males. Fathers also had a higher amino acid distance to the females' MHC as well as a higher total number of MHC supertypes and a higher degree of microsatellite heterozygosity than randomly assigned males. Female cryptic choice may be the underlying mechanism that operates towards an optimization of the genetic constitution of offspring. This is the first study that provides support for the importance of the MHC constitution in post-copulatory mate choice in non-human primates.

  19. The psychology of primate cooperation and competition: a call for realigning research agendas.

    Science.gov (United States)

    Schmelz, Martin; Call, Josep

    2016-01-19

    Cooperation and competition are two key components of social life. Current research agendas investigating the psychological underpinnings of competition and cooperation in non-human primates are misaligned. The majority of work on competition has been done in the context of theory of mind and deception, while work on cooperation has mostly focused on collaboration and helping. The current impression that theory of mind is not necessarily implicated in cooperative activities and that helping could not be an integral part of competition might therefore be rather misleading. Furthermore, theory of mind research has mainly focused on cognitive aspects like the type of stimuli controlling responses, the nature of representation and how those representations are acquired, while collaboration and helping have focused primarily on motivational aspects like prosociality, common goals and a sense of justice and other-regarding concerns. We present the current state of these two bodies of research paying special attention to how they have developed and diverged over the years. We propose potential directions to realign the research agendas to investigate the psychological underpinnings of cooperation and competition in primates and other animals.

  20. Nutritional contributions of insects to primate diets: implications for primate evolution.

    Science.gov (United States)

    Rothman, Jessica M; Raubenheimer, David; Bryer, Margaret A H; Takahashi, Maressa; Gilbert, Christopher C

    2014-06-01

    Insects and other invertebrates form a portion of many living and extinct primate diets. We review the nutritional profiles of insects in comparison with other dietary items, and discuss insect nutrients in relation to the nutritional needs of living primates. We find that insects are incorporated into some primate diets as staple foods whereby they are the majority of food intake. They can also be incorporated as complements to other foods in the diet, providing protein in a diet otherwise dominated by gums and/or fruits, or be incorporated as supplements to likely provide an essential nutrient that is not available in the typical diet. During times when they are very abundant, such as in insect outbreaks, insects can serve as replacements to the usual foods eaten by primates. Nutritionally, insects are high in protein and fat compared with typical dietary items like fruit and vegetation. However, insects are small in size and for larger primates (>1 kg) it is usually nutritionally profitable only to consume insects when they are available in large quantities. In small quantities, they may serve to provide important vitamins and fatty acids typically unavailable in primate diets. In a brief analysis, we found that soft-bodied insects are higher in fat though similar in chitin and protein than hard-bodied insects. In the fossil record, primates can be defined as soft- or hard-bodied insect feeders based on dental morphology. The differences in the nutritional composition of insects may have implications for understanding early primate evolution and ecology.

  1. Primate molecular phylogenetics in a genomic era.

    Science.gov (United States)

    Ting, Nelson; Sterner, Kirstin N

    2013-02-01

    A primary objective of molecular phylogenetics is to use molecular data to elucidate the evolutionary history of living organisms. Dr. Morris Goodman founded the journal Molecular Phylogenetics and Evolution as a forum where scientists could further our knowledge about the tree of life, and he recognized that the inference of species trees is a first and fundamental step to addressing many important evolutionary questions. In particular, Dr. Goodman was interested in obtaining a complete picture of the primate species tree in order to provide an evolutionary context for the study of human adaptations. A number of recent studies use multi-locus datasets to infer well-resolved and well-supported primate phylogenetic trees using consensus approaches (e.g., supermatrices). It is therefore tempting to assume that we have a complete picture of the primate tree, especially above the species level. However, recent theoretical and empirical work in the field of molecular phylogenetics demonstrates that consensus methods might provide a false sense of support at certain nodes. In this brief review we discuss the current state of primate molecular phylogenetics and highlight the importance of exploring the use of coalescent-based analyses that have the potential to better utilize information contained in multi-locus data.

  2. Optogenetics Advances in Primate Visual Pathway.

    Science.gov (United States)

    Jazayeri, Mehrdad; Remington, Evan

    2016-04-06

    In this issue of Neuron, Klein et al. (2016) used cell-type-specific optogenetics and electrical microstimulation to characterize the koniocellular geniculocortical projections in nonhuman primates. Their work offers a powerful platform for refining our understanding of the mechanisms of visual information processing in the lateral geniculate nucleus and primary visual cortex.

  3. Nonhuman primate models in translational regenerative medicine.

    Science.gov (United States)

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

    2014-12-01

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

  4. Variation in the molecular clock of primates.

    Science.gov (United States)

    Moorjani, Priya; Amorim, Carlos Eduardo G; Arndt, Peter F; Przeworski, Molly

    2016-09-20

    Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​.

  5. Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues.

    Science.gov (United States)

    Gonzalez, O A; Novak, M J; Kirakodu, S; Stromberg, A; Nagarajan, R; Huang, C B; Chen, K C; Orraca, L; Martinez-Gonzalez, J; Ebersole, J L

    2015-01-01

    Recent evidence has determined a phenotypic and functional heterogeneity for macrophage populations. This plasticity of macrophage function has been related to specific properties of subsets (M1 and M2) of these cells in inflammation, adaptive immune responses and resolution of tissue destructive processes. This investigation hypothesized that targeted alterations in the distribution of macrophage phenotypes in aged individuals, and with periodontitis would be skewed towards M1 inflammatory macrophages in gingival tissues. The study used a non-human primate model to evaluate gene expression profiles as footprints of macrophage variation in healthy and periodontitis gingival tissues from animals 3-23 years of age and in periodontitis tissues in adult and aged animals. Significant increases in multiple genes reflecting overall increases in macrophage activities were observed in healthy aged tissues, and were significantly increased in periodontitis tissues from both adults and aged animals. Generally, gene expression patterns for M2 macrophages were similar in healthy young, adolescent and adult tissues. However, modest increases were noted in healthy aged tissues, similar to those seen in periodontitis tissues from both age groups. M1 macrophage gene transcription patterns increased significantly over the age range in healthy tissues, with multiple genes (e.g. CCL13, CCL19, CCR7 and TLR4) significantly increased in aged animals. Additionally, gene expression patterns for M1 macrophages were significantly increased in adult health versus periodontitis and aged healthy versus periodontitis. The findings supported a significant increase in macrophages with aging and in periodontitis. The primary increases in both healthy aged tissues and, particularly periodontitis tissues appeared in the M1 phenotype.

  6. Ebola Virus Genome Plasticity as a Marker of Its Passaging History: A Comparison of In Vitro Passaging to Non-Human Primate Infection

    Science.gov (United States)

    2012-11-28

    unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 inserted into the nascent mRNA via stuttering of the EBOV RNA- dependent...read depth were removed from the analysis. Only SNPs present in the population above the 2% threshold are presented in this report. A consensus change...is defined here as a change relative to the published sequence for EBOV-Kik (GenBank accession # AY354458) present in $50% of the population. Below

  7. Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.

    Science.gov (United States)

    Pearson, Mark S; Becker, Luke; Driguez, Patrick; Young, Neil D; Gaze, Soraya; Mendes, Tiago; Li, Xiao-Hong; Doolan, Denise L; Midzi, Nicholas; Mduluza, Takafira; McManus, Donald P; Wilson, R Alan; Bethony, Jeffrey M; Nausch, Norman; Mutapi, Francisca; Felgner, Philip L; Loukas, Alex

    2015-01-01

    Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

  8. Of Monkeys and Men: Immunomic Profiling of Sera from Humans and Non-Human Primates Resistant to Schistosomiasis Reveals Novel Potential Vaccine Candidates

    OpenAIRE

    Pearson, Mark S; Becker, Luke; Driguez, Patrick; Young, Neil D.; Gaze, Soraya; Mendes, Tiago; Li, Xiao-Hong; Doolan, Denise L.; Midzi, Nicholas; MDULUZA, TAKAFIRA; McManus, Donald P.; Wilson, R Alan; Bethony, Jeffrey M.; Nausch, Norman; Mutapi, Francisca

    2015-01-01

    Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed ind...

  9. Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates

    Directory of Open Access Journals (Sweden)

    Mark ePearson

    2015-05-01

    Full Text Available Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80, tetraspanins, glutathione-S-transferases and glucose transporters (SGTP1, as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to Schistosoma japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognised by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

  10. Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates

    OpenAIRE

    Mark ePearson; Luke eBecker; Patrick eDriguez; Neil David Young; Soraya eGaze; Tiago eMendes; Xiao-Hong eLi; Denise eDoolan; Nicholas eMidzi; Takafira eMduluza; Donald eMcManus; Alan eWilson; Jeffrey eBethony; Norman eNausch; Francisca eMutapi

    2015-01-01

    Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed ind...

  11. Validation of a Method for the Assessment of Urinary Neopterin Levels to Monitor Health Status in Non-human-primate Species

    Science.gov (United States)

    Behringer, Verena; Stevens, Jeroen M. G.; Leendertz, Fabian H.; Hohmann, Gottfried; Deschner, Tobias

    2017-01-01

    Determining individual health status is of great importance for a better understanding of life history trade-offs between growth, reproduction, and maintenance. However, existing immunological methods are invasive and therefore not suitable for investigating health status in wild populations. Thus, there is an urgent need for non-invasive methods to assess the immune status of animals. Neopterin is involved in the cell-mediated pathway of the immune response (Th1–type), secreted during the activation of monocytes and macrophages. We investigated if urinary neopterin could serve as a biomarker of health status in bonobos and chimpanzees. First, we performed a chemical validation of a commercial neopterin enzyme immune assay (EIA) for bonobo and chimpanzee urine. We then examined if urinary neopterin levels in bonobos increase during the acute period of respiratory infections. We found that neopterin levels can be reliably measured in urine of the two species with a commercial EIA. Stability experiments revealed considerable changes in urinary neopterin levels in relation to multiple freeze–thaw cycles and extended exposure to room temperature. Exposure to sunlight led to a degradation of urinary neopterin, whereas sample storage up to 2 years did not affect urinary neopterin levels. There was no detectable diurnal variation in neopterin levels, and levels remained very stable across several days in healthy individuals. While urinary neopterin levels were independent of sex, non-adult individuals had higher urinary neopterin levels than adults. Most importantly, there was a significant increase in urinary neopterin levels during a period of respiratory infection. Our results demonstrate that regular urine sample collection would allow for the monitoring of individual health status and disease progression with minimal disturbance of the subjects. In combination with behavioral, life history, and endocrinological parameters, the method can be used to investigate questions related to immunocompetence handicaps or life history trade-offs. PMID:28220080

  12. The utility of rhesus monkey (Macaca mulatta and other non-human primate models for preclinical testing of Leishmania candidate vaccines

    Directory of Open Access Journals (Sweden)

    Gabriel Grimaldi Jr

    2008-11-01

    Full Text Available Leishmaniasis causes significant morbidity and mortality, constituting an important global health problem for which there are few effective drugs. Given the urgent need to identify a safe and effective Leishmania vaccine to help prevent the two million new cases of human leishmaniasis worldwide each year, all reasonable efforts to achieve this goal should be made. This includes the use of animal models that are as close to leishmanial infection in humans as is practical and feasible. Old world monkey species (macaques, baboons, mandrills etc. have the closest evolutionary relatedness to humans among the approachable animal models. The Asian rhesus macaques (Macaca mulatta are quite susceptible to leishmanial infection, develop a human-like disease, exhibit antibodies to Leishmania and parasite-specific T-cell mediated immune responses both in vivo and in vitro, and can be protected effectively by vaccination. Results from macaque vaccine studies could also prove useful in guiding the design of human vaccine trials. This review summarizes our current knowledge on this topic and proposes potential approaches that may result in the more effective use of the macaque model to maximize its potential to help the development of an effective vaccine for human leishmaniasis.

  13. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2011-01-01

    arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged...... in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion...

  14. 1982 Resident's Essay Award: the immunologic effects of lymphoid irradiation in human and non-human primates: cellular changes and the potential for renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Halperin, E.C.; Haas, G.; Dosoretz, D.E.; Gitterman, M.; Barrett, L.; Cosimi, A.B.; Suit, H.D.; Phil, D.

    1983-07-01

    Previous reports have suggested that the immunosuppressive effects of lymphoid irradiation (LI) are related to changes in T cell peripheral blood levels. We prospectively studied 13 patients with Stages I and II Hodgkin's disease before, during, and after a course of LI. Forty to 45Gy delivered to the mantle field in 4-1/2 to 5 weeks was followed by a 3 to 4 week break and 35 to 40 Gy to the paraaortic field. The absolute lymphocyte count prior to LI was 1400 +- 270/mm3. This fell to 597 +- 280/mm3 at the conclusion of LI and returned to 1490 +- 800/mm3 at 7 to 8 months post-LI. Seven previously spleenectomized cynomolgus monkeys received 20Gy of LI in 20 equal daily fractions over a 4 week period through a single anterior field including the cervical, axillary, mediastinal, paraaortic, iliac, and inguinal lymph node chains at a dose rate of 4.6 to 4.8cGy/minute. Renal allografts from unrelated monkey donors were placed following LI. Graft function was monitored by urine output, serum BUN and creatinine, and renal biopsy. Low dose rate LI was well tolerated. The absolute lymphocyte count fell from a pre-LI level of 3080 +- 1227/mm3 to 534 +- 478/mm3 at 1 month post-LI. In 4 animals that received no LI (controls), survival post-transplant was 8 to 11 days prior to death from acute rejection. Five animals received transplants immediately following LI. Four survived 11 to 56 days prior to death of presumed infection. One died at day 45 with rejection. Another group of two animals received transplants 3-1/2 weeks after LI. One died of rejection at day 42. One remains well at day 394 post-transplant.

  15. 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

    the design of short antisense oligonucleotides (12- to 13-mers) that possessed high affinity and increased potency both in vitro and in vivo compared to longer oligonucleotides. The short LNA oligonucleotides were more target specific, and they exhibited the same biodistribution and tissue half......-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...

  16. GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.

    Directory of Open Access Journals (Sweden)

    Peter T Loudon

    Full Text Available BACKGROUND: The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques. METHODOLOGY/PRINCIPAL FINDINGS: Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine. CONCLUSIONS/SIGNIFICANCE: These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.

  17. Effect of palm olein oil in a moderate-fat diet on low-density lipoprotein composition in non-human primates.

    Science.gov (United States)

    van Jaarsveld, Paul J; Benadé, A J Spinnler

    2002-01-01

    Plasma low-density lipoprotein cholesterol (LDL-C) concentrations in vervet monkeys (Cercopithecus aethiops) can be modulated by the type and amount of fat in the diet. There is, however, a paucity of information on the effect of different types and quantity of dietary fat on the plasma LDL composition in vervets. The objective of this study was to determine the effect of different sources of dietary fat on the concentrations and composition of circulating plasma LDL in vervets consuming moderate-fat diets containing either animal fat, sunflower oil or palm olein. Fifty adult male vervets, never exposed to a Western-type atherogenic diet, were randomly assigned to two groups. For 6 weeks 30 vervets were fed a moderate-fat (28%E) moderate-cholesterol (26 mg cholesterol/1000 kJ) diet (MFD) with a polyunsaturated to saturated fatty acid ratio (P/S) of 0.4; 20 vervets were fed a high-fat (34%E) high-cholesterol (98 mg cholesterol/1000 kJ) diet (HFD) with a P/S ratio of 0.6. Fasting blood samples were collected from all 50 vervets for plasma lipid measurements. The 30 vervets receiving the MFD were stratified into three comparable experimental groups of 10 each according to their LDL-C and high-density lipoprotein cholesterol (HDL-C) concentrations and bodyweight. One group continued with the MFD, in which 11%E was derived from lard (MFD-AF); in the other two groups the lard was substituted isocalorically with either sunflower oil (SO) (MFD-SO) or palm olein oil (PO) (MFD-PO). The three groups were fed the respective experimental diets for 24 months and LDL component concentrations and composition were assessed at 6-monthly intervals. In the long-term study the MFD-AF, MFD-SO and MFD-PO groups showed no significant time-specific group differences at 6, 12, 18 or 24 months with regard to the LDL component concentrations, composition, as well as the LDL molecular weight. As expected, after 6 weeks of dietary exposure the HFD group had significantly higher plasma and lipoprotein total cholesterol, LDL component and apolipoprotein AI concentrations, as well as a higher LDL-C : HDL-C ratio compared to the MFD group (P 0.0005). LDL particle size was not significantly different between the HFD and MFD groups, but the HFD group had significantly fewer triacylglycerol and significantly more unesterified cholesterol molecules per LDL particle compared to the MFD group (P 0.0018). PO in a MFD is no different from AF or SO in its effect on LDL component concentrations, composition or particle size. The increased LDL-C concentration seen with the HFD could be accounted for by a more than two-fold increase in the number of circulating LDL particles and not as a result of enrichment of particles with cholesterol.

  18. Radiosynthesis of [{sup 18}F] N-(3-Fluoropropyl)-2-{beta}-Carbomethoxy-3-{beta}-(4-Bromophenyl) Nortropane and the regional brain uptake in non human primate using PET

    Energy Technology Data Exchange (ETDEWEB)

    Chaly, Thomas E-mail: tchaly@nshs.edu; Baldwin, R.M.; Neumeyer, John L.; Hellman, Matthew J.; Dhawan, Vijay; Garg, Pradeep K.; Tamagnan, Gilles; Staley, Julie K.; Al-Tikriti, Mohammed S.; Hou, Yankun; Zoghbi, Sami S.; Gu Xiaohui; Zong, R.; Eidelberg, David

    2004-01-01

    A synthetic procedure for the preparation of [{sup 18}F]FPCBT, an imaging agent for the dopamine transporter (DAT), has been developed. The radiosynthesis was carried out in a two step procedure. Even though the yield was low, we were able to prepare 20 to 30mCi of the product, which was enough for two or three studies. The radiochemical purity was greater than 96%. The in vivo properties of this radiotracer were evaluated using baboon and it showed highest uptake in the striatum. The studies also revealed that the maximum uptake was reached within 7 to 10 minutes post injection. Plasma metabolite analysis indicated that there is only one metabolite and it is less lipophilic than the parent compound. [{sup 18}F]FPCBT displayed good brain uptake and its high target to non target ratio indicate that it is a potential candidate for DAT imaging.

  19. Fusion of the Mycobacterium tuberculosis antigen 85A to an oligomerization domain enhances its immunogenicity in both mice and non-human primates.

    Directory of Open Access Journals (Sweden)

    Alexandra J Spencer

    Full Text Available To prevent important infectious diseases such as tuberculosis, malaria and HIV, vaccines inducing greater T cell responses are required. In this study, we investigated whether fusion of the M. tuberculosis antigen 85A to recently described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could increase T cell responses in pre-clinical vaccine model species. In mice, the fused antigen 85A showed consistent increases in CD4(+ and CD8(+ T cell responses after DNA and MVA vaccination. In rhesus macaques, higher IFN-γ responses were observed in animals vaccinated with MVA-Ag85A IMX313 after both primary and secondary immunizations. In both animal models, fusion to IMX313 induced a quantitative enhancement in the response without altering its quality: multifunctional cytokines were uniformly increased and differentiation into effector and memory T cell subsets was augmented rather than skewed. An extensive in vivo characterization suggests that IMX313 improves the initiation of immune responses as an increase in antigen 85A specific cells was observed as early as day 3 after vaccination. This report demonstrates that antigen multimerization using IMX313 is a simple and effective cross-species method to improve vaccine immunogenicity with potentially broad applicability.

  20. Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Non-Human Primate

    Science.gov (United States)

    2013-10-01

    University). At the onset of the project, research subjects in the form of adult female rhesus monkeys were selected for pre-surgical testing and were...During the first year of the project, we developed an algorithm to ensure selection of suitable subjects for these studies. While the pre-surgical...testing. These algorithms for subject identification, selection and evaluation were also implemented during years 2 and 3 of the project. Prior

  1. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates.

    Science.gov (United States)

    Wang, Changyu; Thudium, Kent B; Han, Minhua; Wang, Xi-Tao; Huang, Haichun; Feingersh, Diane; Garcia, Candy; Wu, Yi; Kuhne, Michelle; Srinivasan, Mohan; Singh, Sujata; Wong, Susan; Garner, Neysa; Leblanc, Heidi; Bunch, R Todd; Blanset, Diann; Selby, Mark J; Korman, Alan J

    2014-09-01

    The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint, limiting bystander tissue damage and preventing the development of autoimmunity during inflammatory responses. PD-1 is expressed by activated T cells and downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD-L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1 on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor and immune cells in the tumor microenvironment undermine antitumor immunity and support its rationale for PD-1 blockade in cancer immunotherapy. This report details the development and characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1 with high affinity and specificity, and effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity was observed with the use of nivolumab and activated T cells as targets. Nivolumab treatment did not induce adverse immune-related events when given to cynomolgus macaques at high concentrations, independent of circulating anti-nivolumab antibodies where observed. These data provide a comprehensive preclinical characterization of nivolumab, for which antitumor activity and safety have been demonstrated in human clinical trials in various solid tumors.

  2. Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates.

    Science.gov (United States)

    Bolton, Diane L; Santra, Sampa; Swett-Tapia, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Mach, Linh; Naim, Hussein; Kozlowski, Pamela A; Lifton, Michelle; Goudsmit, Jaap; Letvin, Norman; Roederer, Mario; Radošević, Katarina

    2012-09-07

    Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses.

  3. A Tetravalent Sub-unit Dengue Vaccine Formulated with Ionizable Cationic Lipid Nanoparticle induces Significant Immune Responses in Rodents and Non-Human Primates.

    Science.gov (United States)

    Swaminathan, Gokul; Thoryk, Elizabeth A; Cox, Kara S; Smith, Jeffrey S; Wolf, Jayanthi J; Gindy, Marian E; Casimiro, Danilo R; Bett, Andrew J

    2016-10-05

    Dengue virus has emerged as an important arboviral infection worldwide. As a complex pathogen, with four distinct serotypes, the development of a successful Dengue virus vaccine has proven to be challenging. Here, we describe a novel Dengue vaccine candidate that contains truncated, recombinant, Dengue virus envelope protein from all four Dengue virus serotypes (DEN-80E) formulated with ionizable cationic lipid nanoparticles (LNPs). Immunization studies in mice, Guinea pigs, and in Rhesus macaques, revealed that LNPs induced high titers of Dengue virus neutralizing antibodies, with or without co-administration or encapsulation of a Toll-Like Receptor 9 agonist. Importantly, LNPs were also able to boost DEN-80E specific CD4+ and CD8+ T cell responses. Cytokine and chemokine profiling revealed that LNPs induced strong chemokine responses without significant induction of inflammatory cytokines. In addition to being highly efficacious, the vaccine formulation proved to be well-tolerated, demonstrating no elevation in any of the safety parameters evaluated. Notably, reduction in cationic lipid content of the nanoparticle dramatically reduced the LNP's ability to boost DEN-80E specific immune responses, highlighting the crucial role for the charge of the LNP. Overall, our novel studies, across multiple species, reveal a promising tetravalent Dengue virus sub-unit vaccine candidate.

  4. Data-driven model comparing the effects of glial scarring and interface interactions on chronic neural recordings in non-human primates

    Science.gov (United States)

    Malaga, Karlo A.; Schroeder, Karen E.; Patel, Paras R.; Irwin, Zachary T.; Thompson, David E.; Bentley, J. Nicole; Lempka, Scott F.; Chestek, Cynthia A.; Patil, Parag G.

    2016-02-01

    Objective. We characterized electrode stability over twelve weeks of impedance and neural recording data from four chronically-implanted Utah arrays in two rhesus macaques, and investigated the effects of glial scarring and interface interactions at the electrode recording site on signal quality using a computational model. Approach. A finite-element model of a Utah array microelectrode in neural tissue was coupled with a multi-compartmental model of a neuron to quantify the effects of encapsulation thickness, encapsulation resistivity, and interface resistivity on electrode impedance and waveform amplitude. The coupled model was then reconciled with the in vivo data. Histology was obtained seventeen weeks post-implantation to measure gliosis. Main results. From week 1-3, mean impedance and amplitude increased at rates of 115.8 kΩ/week and 23.1 μV/week, respectively. This initial ramp up in impedance and amplitude was observed across all arrays, and is consistent with biofouling (increasing interface resistivity) and edema clearing (increasing tissue resistivity), respectively, in the model. Beyond week 3, the trends leveled out. Histology showed that thin scars formed around the electrodes. In the model, scarring could not match the in vivo data. However, a thin interface layer at the electrode tip could. Despite having a large effect on impedance, interface resistivity did not have a noticeable effect on amplitude. Significance. This study suggests that scarring does not cause an electrical problem with regard to signal quality since it does not appear to be the main contributor to increasing impedance or significantly affect amplitude unless it displaces neurons. This, in turn, suggests that neural signals can be obtained reliably despite scarring as long as the recording site has sufficiently low impedance after accumulating a thin layer of biofouling. Therefore, advancements in microelectrode technology may be expedited by focusing on improvements to the recording site-tissue interface rather than elimination of the glial scar.

  5. Successful post-exposure prophylaxis of Ebola infected non-human primates using Ebola glycoprotein-specific equine IgG

    Science.gov (United States)

    Pyankov, Oleg V.; Setoh, Yin Xiang; Bodnev, Sergey A.; Edmonds, Judith H.; Pyankova, Olga G.; Pyankov, Stepan A.; Pali, Gabor; Belford, Shane; Lu, Louis; La, Mylinh; Lovrecz, George; Volchkova, Valentina A.; Chappell, Keith J.; Watterson, Daniel; Marsh, Glenn; Young, Paul R.; Agafonov, Alexander A.; Farmer, Jillann F.; Volchkov, Victor E.; Suhrbier, Andreas; Khromykh, Alexander A.

    2017-01-01

    Herein we describe production of purified equine IgG obtained from horses immunized with plasmid DNA followed by boosting with Kunjin replicon virus-like particles both encoding a modified Ebola glycoprotein. Administration of the equine IgG over 5 days to cynomolgus macaques infected 24 hours previously with a lethal dose of Ebola virus suppressed viral loads by more than 5 logs and protected animals from mortality. Animals generated their own Ebola glycoprotein-specific IgG responses 9–15 days after infection, with circulating virus undetectable by day 15–17. Such equine IgG may find utility as a post-exposure prophylactic for Ebola infection and provides a low cost, scalable alternative to monoclonal antibodies, with extensive human safety data and WHO-standardized international manufacturing capability available in both high and low income countries. PMID:28155869

  6. A Tetravalent Sub-unit Dengue Vaccine Formulated with Ionizable Cationic Lipid Nanoparticle induces Significant Immune Responses in Rodents and Non-Human Primates

    Science.gov (United States)

    Swaminathan, Gokul; Thoryk, Elizabeth A.; Cox, Kara S.; Smith, Jeffrey S.; Wolf, Jayanthi J.; Gindy, Marian E.; Casimiro, Danilo R.; Bett, Andrew J.

    2016-01-01

    Dengue virus has emerged as an important arboviral infection worldwide. As a complex pathogen, with four distinct serotypes, the development of a successful Dengue virus vaccine has proven to be challenging. Here, we describe a novel Dengue vaccine candidate that contains truncated, recombinant, Dengue virus envelope protein from all four Dengue virus serotypes (DEN-80E) formulated with ionizable cationic lipid nanoparticles (LNPs). Immunization studies in mice, Guinea pigs, and in Rhesus macaques, revealed that LNPs induced high titers of Dengue virus neutralizing antibodies, with or without co-administration or encapsulation of a Toll-Like Receptor 9 agonist. Importantly, LNPs were also able to boost DEN-80E specific CD4+ and CD8+ T cell responses. Cytokine and chemokine profiling revealed that LNPs induced strong chemokine responses without significant induction of inflammatory cytokines. In addition to being highly efficacious, the vaccine formulation proved to be well-tolerated, demonstrating no elevation in any of the safety parameters evaluated. Notably, reduction in cationic lipid content of the nanoparticle dramatically reduced the LNP’s ability to boost DEN-80E specific immune responses, highlighting the crucial role for the charge of the LNP. Overall, our novel studies, across multiple species, reveal a promising tetravalent Dengue virus sub-unit vaccine candidate. PMID:27703172

  7. Lymphoid-Like Structures with Distinct B Cell Areas in Kidney Allografts are not Predictive for Graft Rejection. A Non-human Primate Study

    NARCIS (Netherlands)

    Jonker, Margreet; Wubben, Jacqueline A. M.; 't Hart, Bert A.; Haanstra, Krista G.

    2015-01-01

    Kidney allograft biopsies were analyzed for the presence of B cell clusters/aggregates using CD20 staining. Few B cells were found in the diffuse interstitial infiltrates, but clusters of B cells were found in nodular infiltrates. These nodular infiltrates were smaller shortly after transplantation,

  8. Lymphoid-Like Structures with Distinct B Cell Areas in Kidney Allografts are not Predictive for Graft Rejection. A Non-human Primate Study.

    Science.gov (United States)

    Jonker, Margreet; Wubben, Jacqueline A M; 't Hart, Bert A; Haanstra, Krista G

    2015-12-01

    Kidney allograft biopsies were analyzed for the presence of B cell clusters/aggregates using CD20 staining. Few B cells were found in the diffuse interstitial infiltrates, but clusters of B cells were found in nodular infiltrates. These nodular infiltrates were smaller shortly after transplantation, and their size increased over time. At the time of clinical rejection, the nodules often presented as tertiary lymphoid structures (TLS) with lymphoid-like follicles. The presence of small B cell clusters during the first 2 months after transplantation was not associated with early rejection. Even in animals that did not reject their allograft, TLS-like structures were present and could disappear over time. Although TLS were more often found in samples with interstitial fibrosis and tubular atrophy (IFTA), TLS were also present in samples without IFTA. The presence and density of clusters resembling tertiary lymphoid structures most likely reflect an ongoing immune response inside the graft and do not necessarily signify a poor graft outcome or IFTA.

  9. A prominent role for DC-SIGN+ dendritic cells in initiation and dissemination of measles virus infection in non-human primates.

    Directory of Open Access Journals (Sweden)

    Annelies W Mesman

    Full Text Available Measles virus (MV is a highly contagious virus that is transmitted by aerosols. During systemic infection, CD150(+ T and B lymphocytes in blood and lymphoid tissues are the main cells infected by pathogenic MV. However, it is unclear which cell types are the primary targets for MV in the lungs and how the virus reaches the lymphoid tissues. In vitro studies have shown that dendritic cell (DC C-type lectin DC-SIGN captures MV, leading to infection of DCs as well as transmission to lymphocytes. However, evidence of DC-SIGN-mediated transmission in vivo has not been established. Here we identified DC-SIGN(hi DCs as first target cells in vivo and demonstrate that macaque DC-SIGN functions as an attachment receptor for MV. Notably, DC-SIGN(hi cells from macaque broncho-alveolar lavage and lymph nodes transmit MV to B lymphocytes, providing in vivo support for an important role for DCs in both initiation and dissemination of MV infection.

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

    NARCIS (Netherlands)

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

    2015-01-01

    Background: Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combi

  11. The Use of Gamma-H2AX as a Biodosimeter for Total-Body Radiation Exposure in Non-Human Primates

    Science.gov (United States)

    2010-11-23

    radiological incidents to provide optimum possible life- sparing medical procedures to each person. Methods and Findings: We evaluated...materials including lymphocytes, oral cells and skin biopsies have been used for the detection of c-H2AX foci produced by ionizing radiation (IR) (reviewed...irradiation (CT scan, angio- plasty, radiotherapy , etc.) [6,7,9,11,16,17,18], these are not sufficiently comprehensive to regard c-H2AX as

  12. Sublingual Priming with a HIV gp41-Based Subunit Vaccine Elicits Mucosal Antibodies and Persistent B Memory Responses in Non-Human Primates

    Science.gov (United States)

    Bekri, Selma; Bourdely, Pierre; Luci, Carmelo; Dereuddre-Bosquet, Nathalie; Su, Bin; Martinon, Frédéric; Braud, Véronique M.; Luque, Irene; Mateo, Pedro L.; Crespillo, Sara; Conejero-Lara, Francisco; Moog, Christiane; Le Grand, Roger; Anjuère, Fabienne

    2017-01-01

    Persistent B cell responses in mucosal tissues are crucial to control infection against sexually transmitted pathogens like human immunodeficiency virus 1 (HIV-1). The genital tract is a major site of infection by HIV. Sublingual (SL) immunization in mice was previously shown to generate HIV-specific B cell immunity that disseminates to the genital tract. We report here the immunogenicity in female cynomolgus macaques of a SL vaccine based on a modified gp41 polypeptide coupled to the cholera toxin B subunit designed to expose hidden epitopes and to improve mucosal retention. Combined SL/intramuscular (IM) immunization with such mucoadhesive gp41-based vaccine elicited mucosal HIV-specific IgG and IgA antibodies more efficiently than IM immunization alone. This strategy increased the number and duration of gp41-specific IgA secreting cells. Importantly, combined immunization improved the generation of functional antibodies 3 months after vaccination as detected in HIV-neutralizing assays. Therefore, SL immunization represents a promising vaccine strategy to block HIV-1 transmission. PMID:28203239

  13. Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study.

    Science.gov (United States)

    Barro, Ana M Bada; Rivero, Arianna Iglesias; Goñi, Avelina León; Navarro, Bárbara O González; Angarica, Meilis Mesa; Ramírez, Belinda Sánchez; Bedoya, Darel Martínez; Triana, Consuelo González; Rodríguez, Axel Mancebo; Parada, Ángel Casacó

    2012-12-17

    Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n=12). Local reactions were observed at the administration site of four treated animals (n=6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients.

  14. Dental senescence in a long-lived primate links infant survival to rainfall

    Science.gov (United States)

    King, Stephen J.; Arrigo-Nelson, Summer J.; Pochron, Sharon T.; Semprebon, Gina M.; Godfrey, Laurie R.; Wright, Patricia C.; Jernvall, Jukka

    2005-01-01

    Primates tend to be long-lived, and, except for humans, most primate females are able to reproduce into old age. Although aging in most mammals is accompanied by dental senescence due to advanced wear, primates have low-crowned teeth that wear down before old age. Because tooth wear alters crown features gradually, testing whether early dental senescence causes reproductive senescence has been difficult. To identify whether and when low-crowned teeth compromise reproductive success, we used a 20-year field study of Propithecus edwardsi, a rainforest lemur from Madagascar with a maximum lifespan of >27 years. We analyzed tooth wear in three dimensions with dental topographic analysis by using Geographical Information Systems (GIS) technology. We report that tooth wear exposes compensatory shearing blades that maintain dental function for 18 years. Beyond this age, female fertility remains high; however infants survive only if lactation seasons have elevated rainfall. Therefore, low-crowned teeth accommodate wear to a point, after which reproductive success closely tracks environmental fluctuations. These results suggest a tooth wear-determined, but rainfall-mediated, onset of reproductive senescence. Additionally, our study indicates that even subtle changes in climate may affect reproductive success of rainforest species. PMID:16260727

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Nonhuman primate models of polycystic ovary syndrome.

    Science.gov (United States)

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

    2013-07-01

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

  17. Current progress with primate embryonic stem cells.

    Science.gov (United States)

    Byrne, James A; Mitalipov, Shoukhrat M; Wolf, Don P

    2006-05-01

    Embryonic stem cells (ESCs) can proliferate indefinitely, maintain an undifferentiated pluripotent state and differentiate into any cell type. Differentiation of ESCs into various specific cell-types may be able to cure or alleviate the symptoms of various degenerative diseases. Unresolved issues regarding maintaining function, possible apoptosis and tumor formation in vivo mean a prudent approach should be taken towards advancing ESCs into human clinical trials. Rhesus macaques provide the ideal model organism for testing the feasibility, efficacy and safety of ESC based therapies and significant numbers of primate ESC lines are now available. In this review, we will summarize progress in evaluating the genetic and epigenetic integrity of primate ESCs, examine their current use in pre-clinical trials and discuss the potential of producing ESC-derived cell populations that are genetically identical (isogenic) to the host by somatic cell nuclear transfer.

  18. Optogenetics in primates: a shining future?

    Science.gov (United States)

    Gerits, Annelies; Vanduffel, Wim

    2013-07-01

    To understand the functional role of specific neurons in micro- and macro-brain circuitry, health, and disease, it is critical to control their activity precisely. This ambitious goal was first achieved by optogenetics, allowing researchers to increase or decrease neural activity artificially with high temporal and spatial precision. In contrast to the revolution optogenetics engendered in invertebrate and rodent research, only a few studies have reported optogenetic-induced neuronal and behavioral effects in primates. Such studies are nonetheless critical before optogenetics can be applied in a clinical setting. Here, we review the state-of-the-art tools for performing optogenetics in mammals, emphasizing recent neuronal and behavioral results obtained in nonhuman primates.

  19. SOME EVOLUTIONARY TENDENCIES OF NEOTROPICAL PRIMATES

    Directory of Open Access Journals (Sweden)

    THOMAS R. DEFLER

    2009-01-01

    Full Text Available La evolución de los primates neotropicales ha transcurrido aislada o de forma independiente a la de otros primates del mundo, porque poseen una historia evolutiva diferente. Hay varias caracte- rísticas de los primates neotropicales (Platirrinos que son bien distintas a las del viejo mundo (Catarrinos, incluyendo la fórmula dental, el arreglo de las placas craneales, la anatomía del aparato auditivo, pesos corporales menores, una menor adaptación a comportamientos terrestres, algunos poseen colas prensiles y baja diferenciación fenotípica. Formas monógamas de platirri- nos comparten una tendencia de evolución cromosómica rápida con un grupo monógamo de Catarrinos (los Hilobátidos o gibones. La historia filogenética de platirrinos, contrasta con la de catarrinos debido a una división filética antigua (mioceno de los primates del nuevo mundo en dos grupos, con características filogenéticas expresadas en las especies actuales. En contraste, la diferenciación de catarrinos con características que se pueden identificar en especies actuales no sucedió sino hasta el Plio-Pleistoceno. Algunas de estas tendencias, pueden ser explicadas hipotéticamente teniendo en cuenta las características ecológicas planteadas en el nuevo con- tinente; otras tendencias tal vez son el resultado de caminos evolutivos tomados al azar durante la evolución del grupo o, como resultado tanto de deriva genética como de un efecto fundador. Sin embargo, queda mucho trabajo para reconocer la totalidad de las singularidades de los platirrinos y poder apreciar los detalles de su evolución.

  20. Argentine hemorrhagic fever: a primate model.

    Science.gov (United States)

    Weissenbacher, M C; Calello, M A; Colillas, O J; Rondinone, S N; Frigerio, M J

    1979-01-01

    Experimental Junin virus infection of a New World primate, Callithrix jacchus, was evaluated. The virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. Virus was recovered from urine, blood samples and all tissues taken at autopsy. These preliminary observations show that several aspects of the experimental disease in C. jacchus are quite similar to severe natural Argentine hemorrhagic fever of man.

  1. Theory of Auditory Thresholds in Primates

    Science.gov (United States)

    Harrison, Michael J.

    2001-03-01

    The influence of thermal pressure fluctuations at the tympanic membrane has been previously investigated as a possible determinant of the threshold of hearing in humans (L.J. Sivian and S.D. White, J. Acoust. Soc. Am. IV, 4;288(1933).). More recent work has focussed more precisely on the relation between statistical mechanics and sensory signal processing by biological means in creatures' brains (W. Bialek, in ``Physics of Biological Systems: from molecules to species'', H. Flyvberg et al, (Eds), p. 252; Springer 1997.). Clinical data on the frequency dependence of hearing thresholds in humans and other primates (W.C. Stebbins, ``The Acoustic Sense of Animals'', Harvard 1983.) has long been available. I have derived an expression for the frequency dependence of hearing thresholds in primates, including humans, by first calculating the frequency dependence of thermal pressure fluctuations at eardrums from damped normal modes excited in model ear canals of given simple geometry. I then show that most of the features of the clinical data are directly related to the frequency dependence of the ratio of thermal noise pressure arising from without to that arising from within the masking bandwidth which signals must dominate in order to be sensed. The higher intensity of threshold signals in primates smaller than humans, which is clinically observed over much but not all of the human auditory spectrum is shown to arise from their smaller meatus dimensions. note

  2. Emotions, stress, and maternal motivation in primates.

    Science.gov (United States)

    Maestripieri, Dario

    2011-06-01

    Recent research conducted with nonhuman primates confirms that adaptive emotional processes, such as maternal attraction arousability and maternal anxiety arousability, enhance and sustain female motivation to interact with infants, invest in them, and protect them during the postpartum period. Changes in these emotional processes, and concomitant changes in maternal motivation, facilitate the reduction and eventual termination of maternal investment associated with infant weaning. Although laboratory studies of rodents and socially deprived rhesus monkeys have suggested that nulliparous females are neophobic and find infant stimuli aversive, recent primate research indicates that neophobia or aversion to infant stimuli do not occur in females with normal developmental experience. Furthermore, although some rodent and human studies have shown that lactation is accompanied by physiological hyporesponsiveness to stress, other studies of rodents, nonhuman primates, and humans indicate that mothers are highly vulnerable to stress and that stress-induced dysregulation of emotions can interfere with maternal motivation and parenting behavior. It is possible that some aspects of the emotional and experiential regulation of maternal motivation and parental behavior are different in different mammalian species. However, variation in the environments in which subjects are tested and in their developmental experience may also be responsible for the some discrepancies between the results of different studies.

  3. IRC-082451, a novel multitargeting molecule, reduces L-DOPA-induced dyskinesias in MPTP Parkinsonian primates.

    Directory of Open Access Journals (Sweden)

    Romina Aron Badin

    Full Text Available The development of dyskinesias following chronic L-DOPA replacement therapy remains a major problem in the long-term treatment of Parkinson's disease. This study aimed at evaluating the effect of IRC-082451 (base of BN82451, a novel multitargeting hybrid molecule, on L-DOPA-induced dyskinesias (LIDs and hypolocomotor activity in a non-human primate model of PD. IRC-082451 displays multiple properties: it inhibits neuronal excitotoxicity (sodium channel blocker, oxidative stress (antioxidant and neuroinflammation (cyclooxygenase inhibitor and is endowed with mitochondrial protective properties. Animals received daily MPTP injections until stably parkinsonian. A daily treatment with increasing doses of L-DOPA was administered to parkinsonian primates until the appearance of dyskinesias. Then, different treatment regimens and doses of IRC-082451 were tested and compared to the benchmark molecule amantadine. Primates were regularly filmed and videos were analyzed with specialized software. A novel approach combining the analysis of dyskinesias and locomotor activity was used to determine efficacy. This analysis yielded the quantification of the total distance travelled and the incidence of dyskinesias in 7 different body parts. A dose-dependent efficacy of IRC-082451 against dyskinesias was observed. The 5 mg/kg dose was best at attenuating the severity of fully established LIDs. Its effect was significantly different from that of amantadine since it increased spontaneous locomotor activity while reducing LIDs. This dose was effective both acutely and in a 5-day sub-chronic treatment. Moreover, positron emission tomography scans using radiolabelled dopamine demonstrated that there was no direct interference between treatment with IRC-082451 and dopamine metabolism in the brain. Finally, post-mortem analysis indicated that this reduction in dyskinesias was associated with changes in cFOS, FosB and ARC mRNA expression levels in the putamen. The data

  4. Animales genéticamente modificados, primates no humanos. (La visión europea

    Directory of Open Access Journals (Sweden)

    Velayos Castelo, Carmen

    2008-04-01

    Full Text Available European citizens think that more needs to be done to improve the level of welfare/protection of animals used in experiments. In recent years, it has become increasingly apparent that the existing legislation for the protection of animals used in experiments (Directive 86/609/EEC. needs to be revised in order to promote improvements in the welfare of laboratory animals and to further foster the development of alternative methods. The UE citizens’ consultation received the third largest number of responses to a Commission internet consultation ever. Since 1986 important progress has been made in science and new techniques have become available, such as use of transgenic animals, xenotransplantation and cloning. These require specific attention, which the current Directive does not provide for. Nor is the use of animals with a higher degree of neurophysiological sensitivity specifically regulated, such as in the case of non-human primates. This essay wants to reflect about experiments with primates and transgenic animals from the perspective of the institutional european ethics.Los ciudadanos europeos creen que se necesita hacer algo más para mejorar el nivel de bienestar/protección de los animales que son utilizados en experimentos. En los últimos años, se ha hecho cada vez más evidente que la legislación actual para la protección de los animales utilizados en experimentación (Directiva 86/609(EEC necesita ser revisada para promover mejoras en el bienestar de los animales de laboratorio, así como para facilitar el desarrollo de métodos alternativos. La consulta de ciudadanos europeos ha recibido el tercer número más alto de respuestas que ha tenido jamás una consulta de la Comisión por internet. Desde 1986, ha habido importantes progresos en ciencia y hay nuevas técnicas disponibles, como la utilización de animales transgénicos, los xenotrasplantes y la clonación. Dichas técnicas requieren una atención específica que la

  5. Comparative Triceps Surae Morphology in Primates: A Review

    OpenAIRE

    Hanna, Jandy B.; Daniel Schmitt

    2011-01-01

    Primate locomotor evolution, particularly the evolution of bipedalism, is often examined through morphological studies. Many of these studies have examined the uniqueness of the primate forelimb, and others have examined the primate hip and thigh. Few data exist, however, regarding the myology and function of the leg muscles, even though the ankle plantar flexors are highly important during human bipedalism. In this paper, we draw together data on the fiber type and muscle mass variation in t...

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

    OpenAIRE

    2009-01-01

    Alopecia (hair loss) occurs in some nonhuman primates housed in captivity and is of concern to colony managers and veterinarians. Here we review the characteristics, potential causes, and treatments for this condition. Although we focus on nonhuman primates, relevant research on other mammalian species is discussed also, due to the relative paucity of studies on alopecia in the primate literature. We first discuss the cycle of hair growth and explain how this cycle can be disrupted to produce...

  7. Eye size at birth in prosimian primates: life history correlates and growth patterns.

    Directory of Open Access Journals (Sweden)

    Joshua R Cummings

    Full Text Available BACKGROUND: Primates have large eyes relative to head size, which profoundly influence the ontogenetic emergence of facial form. However, growth of the primate eye is only understood in a narrow taxonomic perspective, with information biased toward anthropoids. METHODOLOGY/PRINCIPAL FINDINGS: We measured eye and bony orbit size in perinatal prosimian primates (17 strepsirrhine taxa and Tarsius syrichta to infer the extent of prenatal as compared to postnatal eye growth. In addition, multiple linear regression was used to detect relationships of relative eye and orbit diameter to life history variables. ANOVA was used to determine if eye size differed according to activity pattern. In most of the species, eye diameter at birth measures more than half of that for adults. Two exceptions include Nycticebus and Tarsius, in which more than half of eye diameter growth occurs postnatally. Ratios of neonate/adult eye and orbit diameters indicate prenatal growth of the eye is actually more rapid than that of the orbit. For example, mean neonatal transverse eye diameter is 57.5% of the adult value (excluding Nycticebus and Tarsius, compared to 50.8% for orbital diameter. If Nycticebus is excluded, relative gestation age has a significant positive correlation with relative eye diameter in strepsirrhines, explaining 59% of the variance in relative transverse eye diameter. No significant differences were found among species with different activity patterns. CONCLUSIONS/SIGNIFICANCE: The primate developmental strategy of relatively long gestations is probably tied to an extended period of neural development, and this principle appears to apply to eye growth as well. Our findings indicate that growth rates of the eye and bony orbit are disassociated, with eyes growing faster prenatally, and the growth rate of the bony orbit exceeding that of the eyes after birth. Some well-documented patterns of orbital morphology in adult primates, such as the enlarged orbits

  8. The adaptive value of primate color vision for predator detection.

    Science.gov (United States)

    Pessoa, Daniel Marques Almeida; Maia, Rafael; de Albuquerque Ajuz, Rafael Cavalcanti; De Moraes, Pedro Zurvaino Palmeira Melo Rosa; Spyrides, Maria Helena Constantino; Pessoa, Valdir Filgueiras

    2014-08-01

    The complex evolution of primate color vision has puzzled biologists for decades. Primates are the only eutherian mammals that evolved an enhanced capacity for discriminating colors in the green-red part of the spectrum (trichromatism). However, while Old World primates present three types of cone pigments and are routinely trichromatic, most New World primates exhibit a color vision polymorphism, characterized by the occurrence of trichromatic and dichromatic females and obligatory dichromatic males. Even though this has stimulated a prolific line of inquiry, the selective forces and relative benefits influencing color vision evolution in primates are still under debate, with current explanations focusing almost exclusively at the advantages in finding food and detecting socio-sexual signals. Here, we evaluate a previously untested possibility, the adaptive value of primate color vision for predator detection. By combining color vision modeling data on New World and Old World primates, as well as behavioral information from human subjects, we demonstrate that primates exhibiting better color discrimination (trichromats) excel those displaying poorer color visions (dichromats) at detecting carnivoran predators against the green foliage background. The distribution of color vision found in extant anthropoid primates agrees with our results, and may be explained by the advantages of trichromats and dichromats in detecting predators and insects, respectively.

  9. Diurnality, nocturnality, and the evolution of primate visual systems.

    Science.gov (United States)

    Ankel-Simons, F; Rasmussen, D T

    2008-01-01

    Much of the recent research on the evolution of primate visual systems has assumed that a minimum number of shifts have occurred in circadian activity patterns over the course of primate evolution. The evolutionary origins of key higher taxonomic groups have been interpreted by some researchers as a consequence of a rare shift from nocturnality to diurnality (e.g., Anthropoidea) or from diurnality to nocturnality (e.g., Tarsiidae). Interpreting the evolution of primate visual systems with an ecological approach without parsimony constraints suggests that the evolutionary transitions in activity pattern are more common than what would be allowed by parsimony models, and that such transitions are probably less important in the origin of higher level taxa. The analysis of 17 communities of primates distributed widely around the world and through geological time shows that primate communities consistently contain both nocturnal and diurnal forms, regardless of the taxonomic sources of the communities. This suggests that primates in a community will adapt their circadian pattern to fill empty diurnal or nocturnal niches. Several evolutionary transitions from one pattern to the other within narrow taxonomic groups are solidly documented, and these cases probably represent a small fraction of such transitions throughout the Cenozoic. One or more switches have been documented among platyrrhine monkeys, Malagasy prosimians, Eocene omomyids, Eocene adapoids, and early African anthropoids, with inconclusive but suggestive data within tarsiids. The interpretation of living and extinct primates as fitting into one of two diarhythmic categories is itself problematic, because many extant primates show significant behavioral activity both nocturnally and diurnally. Parsimony models routinely interpret ancestral primates to have been nocturnal, but analyses of morphological and genetic data indicate that they may have been diurnal, or that early primate radiations were likely to

  10. The Ethics of Infection Challenges in Primates.

    Science.gov (United States)

    Barnhill, Anne; Joffe, Steven; Miller, Franklin G

    2016-07-01

    In the midst of the recent Ebola outbreak, scientific developments involving infection challenge experiments on nonhuman primates (NHPs) sparked hope that successful treatments and vaccines may soon become available. Yet these studies pose a stark ethical quandary. On the one hand, they represent an important step in developing novel therapies and vaccines for Ebola and the Marburg virus, with the potential to save thousands of human lives and to protect whole communities from devastation; on the other hand, they intentionally expose sophisticated animals to severe suffering and a high risk of death. Other studies that infect NHPs with a lethal disease in order to test interventions that may prove beneficial for humans pose the same ethical difficulty. Some advocates have argued that all research on primates should be phased out, and ethicists have questioned whether a moral justification of primate research is possible. A 2010 European Union directive banned virtually all research on great apes, and 2013 guidelines from the National Institutes of Health (NIH), based upon recommendations in an influential 2011 Institute of Medicine (IOM) report, eliminated most biomedical research with chimpanzees in the United States. But studies involving other NHPs face no comparable restrictions. Should research on NHPs other than great apes be subject to tighter restrictions than it currently is? In this article, we explore this general question in the context of one particular type of biomedical research: infection challenge studies. We advocate a presumptive prohibition on infection challenge experiments in NHPs, but we also argue that exceptions to this prohibition are permissible, subject to strict substantive and procedural safeguards, when necessary to avert substantial loss of human life or severe morbidity for a substantial number of people.

  11. Trabecular bone structure in the primate wrist.

    Science.gov (United States)

    Schilling, Ann-Marie; Tofanelli, Sergio; Hublin, Jean-Jacques; Kivell, Tracy L

    2014-05-01

    Trabecular (or cancellous) bone has been shown to respond to mechanical loading throughout ontogeny and thus can provide unique insight into skeletal function and locomotion in comparative studies of living and fossil mammalian morphology. Trabecular bone of the hand may be particularly functionally informative because the hand has more direct contact with the substrate compared with the remainder of the forelimb during locomotion in quadrupedal mammals. This study investigates the trabecular structure within the wrist across a sample of haplorhine primates that vary in locomotor behaviour (and thus hand use) and body size. High-resolution microtomographic scans were collected of the lunate, scaphoid, and capitate in 41 individuals and eight genera (Homo, Gorilla, Pan, Papio, Pongo, Symphalangus, Hylobates, and Ateles). We predicted that particular trabecular parameters would 1) vary across suspensory, quadrupedal, and bipedal primates based on differences in hand use and load, and 2) scale with carpal size following similar allometric patterns found previously in other skeletal elements across a larger sample of mammals and primates. Analyses of variance (trabecular parameters analysed separately) and principal component analyses (trabecular parameters analysed together) revealed no clear functional signal in the trabecular structure of any of the three wrist bones. Instead, there was a large degree of variation within suspensory and quadrupedal locomotor groups, as well as high intrageneric variation within some taxa, particularly Pongo and Gorilla. However, as predicted, Homo sapiens, which rarely use their hands for locomotion and weight support, were unique in showing lower relative bone volume (BV/TV) compared with all other taxa. Furthermore, parameters used to quantify trabecular structure within the wrist scale with size generally following similar allometric patterns found in trabeculae of other mammalian skeletal elements. We discuss the challenges

  12. Earliest known simian primate found in Algeria.

    Science.gov (United States)

    Godinot, M; Mahboubi, M

    1992-05-28

    The record of early fossil Simiiformes (Anthropoidea) from the Late Eocene and Early Oligocene of Africa and the Arabian Peninsula has increased dramatically in recent years. We report here the discovery of a new, diminutive and much older (Early or Middle Eocene) simian from an Algerian locality, Glib Zegdou. This species is smaller than any other living or fossil African simiiform. Derived similarities shared with Aegyptopithecus suggest that the new genus is more closely related to propliopithecines than to oligopithecines, implying that these two subfamilies differentiated during the Early Eocene. The new discovery confirms predictions about the great antiquity of Simiiformes and emphasizes a long and endemic African history for higher primates.

  13. Cognitive competencies - Products of genes, experience, and technology. [for training of primates

    Science.gov (United States)

    Rumbaugh, Duane M.; Savage-Rumbaugh, E. S.

    1992-01-01

    The paper examines methods used in studying cognitive competency in primates. Citing experiments on teaching language skills to chimpanzees, it is shown that some methods used for inquiry might lead to the cultivation and generation of new competencies, and specifically to the development of observational and relational learning skills. It is noted that methods can also limit the generality of conclusions; erroneous conclusions may be made based on certain generally accepted methods, whereby the research might be treatments that profoundly determine the assessment of dependent variables. Particular attention is given to the role of age in learning, showing that young primates can be taught the meaning of lexigrams and many specific tasks in much shorter time than adults; on the basis of these experiments, it was concluded that cultural gains did evolve primarily as a consequence of context within which infants were growing.

  14. Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail.

    Science.gov (United States)

    Kugelman, Jeffrey R; Kugelman-Tonos, Johanny; Ladner, Jason T; Pettit, James; Keeton, Carolyn M; Nagle, Elyse R; Garcia, Karla Y; Froude, Jeffrey W; Kuehne, Ana I; Kuhn, Jens H; Bavari, Sina; Zeitlin, Larry; Dye, John M; Olinger, Gene G; Sanchez-Lockhart, Mariano; Palacios, Gustavo F

    2015-09-29

    MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape.

  15. The INIA19 template and NeuroMaps atlas for primate brain image parcellation and spatial normalization

    Directory of Open Access Journals (Sweden)

    Torsten eRohlfing

    2012-12-01

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

  16. Prevalence of Salmonella serotypes isolated in Spain from human and non human sources (1983-1987).

    Science.gov (United States)

    Echeita, M A; Usera, M A

    1989-09-01

    Salmonella serotypes over a five year period were studied in order to know their prevalence in Spain. The Salmonella Reference Centre received a total of 17,612 strains from 1983-1987. The majority (16,133) were of human origin and only 1,479 strains were isolated from non-human sources. The serotyping yielded 100 different serotypes, Salmonella enterica serotype Enteritidis (8) being the commonest in both groups, 61.18% of human origin and 31.91% of non-human origin. Salmonella enterica serotype Typhimurium the commonest serotype in many countries, occupies second place in our results with the following percentages 11.87% and 9.67% respectively. Among the strains of human origin Salmonella enterica serotype Typhi occupies fourth place (3.24%). This is very low compared with the high number of clinically diagnosed typhoid fever cases declared in the country: over 5,000 cases per year.

  17. ISFG: Recommendations regarding the use of non-human (animal) DNA in forensic genetic investigations

    DEFF Research Database (Denmark)

    Linacre, A.; Gusmão, L.; Hecht, W.;

    2010-01-01

    The use of non-human DNA typing in forensic science investigations, and specifically that from animal DNA, is ever increasing. The term animal DNA in this document refers to animal species encountered in a forensic science examination but does not include human DNA. Non-human DNA may either be......: the trade and possession of a species, or products derived from a species, which is contrary to legislation; as evidence where the crime is against a person or property; instances of animal cruelty; or where the animal is the offender. The first instance is addressed by determining the species present......, and the other scenarios can often be addressed by assigning a DNA sample to a particular individual organism. Currently there is little standardization of methodologies used in the forensic analysis of animal DNA or in reporting styles. The recommendations in this document relate specifically to animal DNA...

  18. Developmental processes and canine dimorphism in primate evolution.

    Science.gov (United States)

    Schwartz, Gary T; Miller, Ellen R; Gunnell, Gregg F

    2005-01-01

    Understanding the evolutionary history of canine sexual dimorphism is important for interpreting the developmental biology, socioecology and phylogenetic position of primates. All current evidence for extant primates indicates that canine dimorphism is achieved through bimaturism rather than via differences in rates of crown formation time. Using incremental growth lines, we charted the ontogeny of canine formation within species of Eocene Cantius, the earliest known canine-dimorphic primate, to test whether canine dimorphism via bimaturism was developmentally canalized early in primate evolution. Our results show that canine dimorphism in Cantius is achieved primarily through different rates of crown formation in males and females, not bimaturism. This is the first demonstration of rate differences resulting in canine dimorphism in any primate and therefore suggests that canine dimorphism is not developmentally homologous across Primates. The most likely interpretation is that canine dimorphism has been selected for at least twice during the course of primate evolution. The power of this approach is its ability to identify underlying developmental processes behind patterns of morphological similarity, even in long-extinct primate species.

  19. Primate bites in Gibraltar--minor casualty quirk?

    Science.gov (United States)

    Campbell, A C

    1989-10-01

    In one year 55 patients presented to the casualty department of St Bernard's Hospital, Gibraltar, with a primate bite. The implications of such wounds on the health of these patients is contrasted with the morbidity and mortality associated with primate bites in the African subcontinent.

  20. Beware of primate life history data: a plea for data standards and a repository.

    Directory of Open Access Journals (Sweden)

    Carola Borries

    Full Text Available Life history variables such as the age at first reproduction and the interval between consecutive births are measures of investment in growth and reproduction in a particular population or species. As such they allow for meaningful comparisons of the speed of growth and reproduction between species and between larger taxa. Especially in primates such life history research has far reaching implications and has led for instance to the "grandmother hypothesis". Other links have been proposed with respect to dietary adaptations: Because protein is essential for growth and one of the primary sources of protein, leaves, occurs much less seasonally than fruits, it has been predicted that folivorous primates should grow faster compared to frugivorous ones. However, when comparing folivorous Asian colobines with frugivorous Asian macaques we recently documented a longer, instead of a shorter gestation length in folivores while age at first reproduction and interbirth interval did not differ. This supports earlier findings for Malagasy lemurs in which all life history variables tested were significantly longer in folivores compared to frugivores. Wondering why these trends were not apparent sooner, we tried to reconstruct our results for Asian primates with data from four popular life history compilations. However, this attempt failed; even the basic, allometric relationship with adult female body mass that is typical for life history variables could not be recovered. This negative result hints at severe problems with data quality. Here we show that data quality can be improved significantly by standardizing the variables and by controlling for factors such as nutritional conditions or infant mortality. Ideally, in the future, revised primate life history data should be collated in a central database accessible to everybody. In the long run such an initiative should be expanded to include all mammalian species.

  1. Differences in the Evaluation of Generic Statements About Human and Non-Human Categories.

    Science.gov (United States)

    Tasimi, Arber; Gelman, Susan A; Cimpian, Andrei; Knobe, Joshua

    2016-11-04

    Generic statements (e.g., "Birds lay eggs") express generalizations about categories. Current theories suggest that people should be especially inclined to accept generics that involve threatening information. However, previous tests of this claim have focused on generics about non-human categories, which raises the question of whether this effect applies as readily to human categories. In Experiment 1, adults were more likely to accept generics involving a threatening (vs. a non-threatening) property for artifacts, but this negativity bias did not also apply to human categories. Experiment 2 examined an alternative hypothesis for this result, and Experiments 3 and 4 served as conceptual replications of the first experiment. Experiment 5 found that even preschoolers apply generics differently for humans and artifacts. Finally, Experiment 6 showed that these effects reflect differences between human and non-human categories more generally, as adults showed a negativity bias for categories of non-human animals, but not for categories of humans. These findings suggest the presence of important, early-emerging domain differences in people's judgments about generics.

  2. The outer subventricular zone and primate-specific cortical complexification.

    Science.gov (United States)

    Dehay, Colette; Kennedy, Henry; Kosik, Kenneth S

    2015-02-18

    Evolutionary expansion and complexification of the primate cerebral cortex are largely linked to the emergence of the outer subventricular zone (OSVZ), a uniquely structured germinal zone that generates the expanded primate supragranular layers. The primate OSVZ departs from rodent germinal zones in that it includes a higher diversity of precursor types, inter-related in bidirectional non-hierarchical lineages. In addition, primate-specific regulatory mechanisms are operating in primate cortical precursors via the occurrence of novel miRNAs. Here, we propose that the origin and evolutionary importance of the OSVZ is related to genetic changes in multiple regulatory loops and that cell-cycle regulation is a favored target for evolutionary adaptation of the cortex.

  3. What Cognitive Representations Support Primate Theory of Mind?

    Science.gov (United States)

    Martin, Alia; Santos, Laurie R

    2016-05-01

    Much recent work has examined the evolutionary origins of human mental state representations. This work has yielded strikingly consistent results: primates show a sophisticated ability to track the current and past perceptions of others, but they fail to represent the beliefs of others. We offer a new account of the nuanced performance of primates in theory of mind (ToM) tasks. We argue that primates form awareness relations tracking the aspects of reality that other agents are aware of. We contend that these awareness relations allow primates to make accurate predictions in social situations, but that this capacity falls short of our human-like representational ToM. We end by explaining how this new account makes important new empirical predictions about primate ToM.

  4. Primate polonium metabolic models and their use in estimation of systemic radiation doses from bioassay data. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, N. [New York Univ. Medical Center, Tuxedo, NY (United States). Dept. of Environmental Medicine

    1989-03-15

    A Polonium metabolic model was derived and incorporated into a Fortran algorithm which estimates the systemic radiation dose from {sup 210}Po when applied to occupational urine bioassay data. The significance of the doses estimated are examined by defining the degree of uncertainty attached to them through comprehensive statistical testing procedures. Many parameters necessary for dosimetry calculations (such as organ partition coefficients and excretion fractions), were evaluated from metabolic studies of {sup 210}Po in non-human primates. Two tamarins and six baboons were injected intravenously with {sup 210}Po citrate. Excreta and blood samples were collected. Five of the baboons were sacrificed at times ranging from 1 day to 3 months post exposure. Complete necropsies were performed and all excreta and the majority of all skeletal and tissue samples were analyzed radiochemically for their {sup 210}Po content. The {sup 210}Po excretion rate in the baboon was more rapid than in the tamarin. The biological half-time of {sup 210}Po excretion in the baboon was approximately 15 days while in the tamarin, the {sup 210}Po excretion rate was in close agreement with the 50 day biological half-time predicted by ICRP 30. Excretion fractions of {sup 210}Po in the non-human primates were found to be markedly different from data reported elsewhere in other species, including man. A thorough review of the Po urinalysis procedure showed that significant recovery losses resulted when metabolized {sup 210}Po was deposited out of raw urine. Polonium-210 was found throughout the soft tissues of the baboon but not with the partition coefficients for liver, kidneys, and spleen that are predicted by the ICRP 30 metabolic model. A fractional distribution of 0.29 for liver, 0.07 for kidneys, and 0.006 for spleen was determined. Retention times for {sup 210}Po in tissues are described by single exponential functions with biological half-times ranging from 15 to 50 days.

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

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    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.

  6. Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates.

    Science.gov (United States)

    Cicin-Sain, Luka; Smyk-Pearson, Susan; Smyk-Paerson, Sue; Currier, Noreen; Byrd, Laura; Koudelka, Caroline; Robinson, Tammie; Swarbrick, Gwendolyn; Tackitt, Shane; Legasse, Alfred; Fischer, Miranda; Nikolich-Zugich, Dragana; Park, Byung; Hobbs, Theodore; Doane, Cynthia J; Mori, Motomi; Axthelm, Michael K; Axthelm, Michael T; Lewinsohn, Deborah A; Nikolich-Zugich, Janko

    2010-06-15

    Aging is usually accompanied by diminished immune protection upon infection or vaccination. Although aging results in well-characterized changes in the T cell compartment of long-lived, outbred, and pathogen-exposed organisms, their relevance for primary Ag responses remain unclear. Therefore, it remains unclear whether and to what extent the loss of naive T cells, their partial replacement by oligoclonal memory populations, and the consequent constriction of TCR repertoire limit the Ag responses in aging primates. We show in this study that aging rhesus monkeys (Macaca mulatta) exhibit poor CD8 T cell and B cell responses in the blood and poor CD8 responses in the lungs upon vaccination with the modified vaccinia strain Ankara. The function of APCs appeared to be maintained in aging monkeys, suggesting that the poor response was likely intrinsic to lymphocytes. We found that the loss of naive CD4 and CD8 T cells, and the appearance of persisting T cell clonal expansions predicted poor CD8 responses in individual monkeys. There was strong correlation between early CD8 responses in the transitory CD28+ CD62L- CD8+ T cell compartment and the peak Ab titers upon boost in individual animals, as well as a correlation of both parameters of immune response to the frequency of naive CD8+ T cells in old but not in adult monkeys. Therefore, our results argue that T cell repertoire constriction and naive cell loss have prognostic value for global immune function in aging primates.

  7. Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

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    Joseph W Golden

    Full Text Available Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA. We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV nonhuman primate (NHP challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

  8. Dynamic Actin Gene Family Evolution in Primates

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    Liucun Zhu

    2013-01-01

    Full Text Available Actin is one of the most highly conserved proteins and plays crucial roles in many vital cellular functions. In most eukaryotes, it is encoded by a multigene family. Although the actin gene family has been studied a lot, few investigators focus on the comparison of actin gene family in relative species. Here, the purpose of our study is to systematically investigate characteristics and evolutionary pattern of actin gene family in primates. We identified 233 actin genes in human, chimpanzee, gorilla, orangutan, gibbon, rhesus monkey, and marmoset genomes. Phylogenetic analysis showed that actin genes in the seven species could be divided into two major types of clades: orthologous group versus complex group. Codon usages and gene expression patterns of actin gene copies were highly consistent among the groups because of basic functions needed by the organisms, but much diverged within species due to functional diversification. Besides, many great potential pseudogenes were found with incomplete open reading frames due to frameshifts or early stop codons. These results implied that actin gene family in primates went through “birth and death” model of evolution process. Under this model, actin genes experienced strong negative selection and increased the functional complexity by reproducing themselves.

  9. Primate Socioecology: New Insights from Males

    Science.gov (United States)

    Kappeler, Peter M.

    Primate males have only recently returned to the center stage of socioecological research. This review surveys new studies that examine variation in the behavior of adult males and their role in social evolution. It is shown that group size, composition, and social behavior are determined not only by resource distribution, predation risk, and other ecological factors, but that life history traits and social factors, especially those related to sexual coercion, can have equally profound consequences for social systems. This general point is illustrated by examining male behavior at three levels: the evolution of permanent associations between males and females, the causes and consequences of variation in the number of males between group-living species, and the determinants of social relationships within and between the sexes. Direct and indirect evidence reviewed in connection with all three questions indicates that the risk of infanticide has been a pervasive force in primate social evolution. Several areas are identified for future research on male life histories that should contribute to a better understanding of male reproductive strategies and corresponding female counterstrategies.

  10. Unexpected demography in the recovery of an endangered primate population.

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    Karen B Strier

    Full Text Available Assessments of the status of endangered species have focused on population sizes, often without knowledge of demographic and behavioral processes underlying population recovery. We analyzed demographic data from a 28-year study of a critically endangered primate, the northern muriqui, to investigate possible changes in demographic rates as this population recovered from near extirpation. As the population increased from 60 to nearly 300 individuals, its growth rate declined due to increased mortality and male-biased birth sex ratios; the increased mortality was not uniform across ages and sexes, and there has been a recent increase in mortality of prime-aged males. If not for a concurrent increase in fertility rates, the population would have stabilized at 200 individuals instead of continuing to grow. The unexpected increase in fertility rates and in adult male mortality can be attributed to the muriquis' expansion of their habitat by spending more time on the ground. The demographic consequences of this behavioral shift must be incorporated into management tactics for this population and emphasize the importance of understanding demographic rates in the recovery of endangered species.

  11. Refractive power and biometric properties of the nonhuman primate isolated crystalline lens.

    Science.gov (United States)

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

    2010-04-01

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

  12. Dating the age of the SIV lineages that gave rise to HIV-1 and HIV-2.

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    Joel O Wertheim

    2009-05-01

    Full Text Available Great strides have been made in understanding the evolutionary history of simian immunodeficiency virus (SIV and the zoonoses that gave rise to HIV-1 and HIV-2. What remains unknown is how long these SIVs had been circulating in non-human primates before the transmissions to humans. Here, we use relaxed molecular clock dating techniques to estimate the time of most recent common ancestor for the SIVs infecting chimpanzees and sooty mangabeys, the reservoirs of HIV-1 and HIV-2, respectively. The date of the most recent common ancestor of SIV in chimpanzees is estimated to be 1492 (1266-1685, and the date in sooty mangabeys is estimated to be 1809 (1729-1875. Notably, we demonstrate that SIV sequences sampled from sooty mangabeys possess sufficient clock-like signal to calibrate a molecular clock; despite the differences in host biology and viral dynamics, the rate of evolution of SIV in sooty mangabeys is indistinguishable from that of its human counterpart, HIV-2. We also estimate the ages of the HIV-2 human-to-human transmissible lineages and provide the first age estimate for HIV-1 group N at 1963 (1948-1977. Comparisons between the SIV most recent common ancestor dates and those of the HIV lineages suggest a difference on the order of only hundreds of years. Our results suggest either that SIV is a surprisingly young lentiviral lineage or that SIV and, perhaps, HIV dating estimates are seriously compromised by unaccounted-for biases.

  13. Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates.

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    Wilmon F Grant

    Full Text Available To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD contained equivalent levels of n-3 fatty acids (FA's and higher levels of n-6 FA's than the control diet (CTR, we found significant decreases in docosahexaenoic acid (DHA and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

  14. Different Evolutionary Origins for the Reach and the Grasp: An Explanation for Dual Visuomotor Channels in Primate Parietofrontal Cortex

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    Jenni M Karl

    2013-12-01

    Full Text Available The Dual Visuomotor Channel Theory proposes that manual prehension consists of two temporally integrated movements, each subserved by distinct visuomotor pathways in occipitoparietofrontal cortex. The Reach is mediated by a dorsomedial pathway and transports the hand in relation to the target’s extrinsic properties (i.e., location and orientation. The Grasp is mediated by a dorsolateral pathway and opens, preshapes, and closes the hand in relation to the target’s intrinsic properties (i.e., size and shape. Here, neuropsychological, developmental, and comparative evidence is reviewed to show that the Reach and the Grasp have different evolutionary origins. First, the removal or degradation of vision causes prehension to decompose into its constituent Reach and Grasp components, which are then executed in sequence or isolation. Similar decomposition occurs in optic ataxic patients following cortical injury to the Reach and Grasp pathways and after corticospinal tract lesions in non-human primates. Second, early nonvisual PreReach and PreGrasp movements develop into mature Reach and Grasp movements but are only integrated under visual control after a prolonged developmental period. Third, comparative studies reveal many similarities between stepping movements and the Reach and between food handling movements and the Grasp, suggesting that the Reach and Grasp are derived from different evolutionary antecedents. The evidence is discussed in relation to the ideas that dual visuomotor channels in primate parietofrontal cortex emerged as a result of distinct evolutionary origins for the Reach and Grasp; that foveated vision in primates serves to integrate the Reach and Grasp into a single prehensile act; and, that flexible recombination of discrete Reach and Grasp movements under various forms of sensory and cognitive control can produce adaptive behavior.

  15. Phylogenetic relations between microbats, megabats and primates (Mammalia: Chiroptera and Primates).

    Science.gov (United States)

    Pettigrew, J D; Jamieson, B G; Robson, S K; Hall, L S; McAnally, K I; Cooper, H M

    1989-11-30

    We examine the paraphylectic hypothesis of bat origins, both in the light of previous discussions, and in the light of new evidence from our analyses of neurological traits and wing morphology. Megabats share with primates a variety of complex details in the organization of neural pathways that have not been found in any other mammalian group, particularly not in microbats. The features previously used to link microbats and megabats have been examined and found to be questionable bases for support of a monophyletic origin. In particular, morphological analyses of the musculoskeletal adaptations associated with the flight apparatus are consistent with two separate origins of the mammalian wing. Taken together, these analyses suggest that megabats evolved from an early branch of the primate lineage. This branch was comprised of moderate-sized, phytophagous gliders, of which the other living descendants are the dermopterans. Microbats, in contrast, probably evolved much earlier from small, agile insectivores whose forelimbs had long metacarpals in relation to their phalanges.

  16. SOME EVOLUTIONARY TENDENCIES OF NEOTROPICAL PRIMATES: Algunas tendencias evolutivas de los primates neotropicales

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    THOMAS R. DEFLER

    Full Text Available La evolución de los primates neotropicales ha transcurrido aislada o de forma independiente a la de otros primates del mundo, porque poseen una historia evolutiva diferente. Hay varias características de los primates neotropicales (Platirrinos que son bien distintas a las del viejo mundo (Catarrinos, incluyendo la fórmula dental, el arreglo de las placas craneales, la anatomía del aparato auditivo, pesos corporales menores, una menor adaptación a comportamientos terrestres, algunos poseen colas prensiles y baja diferenciación fenotípica. Formas monógamas de platirrinos comparten una tendencia de evolución cromosómica rápida con un grupo monógamo de Catarrinos (los Hilobátidos o gibones. La historia filogenética de platirrinos, contrasta con la de catarrinos debido a una división filética antigua (mioceno de los primates del nuevo mundo en dos grupos, con características filogenéticas expresadas en las especies actuales. En contraste, la diferenciación de catarrinos con características que se pueden identificar en especies actuales no sucedió sino hasta el Plio-Pleistoceno. Algunas de estas tendencias, pueden ser explicadas hipotéticamente teniendo en cuenta las características ecológicas planteadas en el nuevo continente; otras tendencias tal vez son el resultado de caminos evolutivos tomados al azar durante la evolución del grupo o, como resultado tanto de deriva genética como de un efecto fundador. Sin embargo, queda mucho trabajo para reconocer la totalidad de las singularidades de los platirrinos y poder apreciar los detalles de su evolución.The evolution of neotropical primates has occurred isolated from other primates of the world, resulting in a distinct evolutionary history. Various characteristics of neotropical primates (Platyrrhini are quite distinct from those of the Old World (Catarrhini, including the dental formula, the position of cranial plates, the anatomy of the auditory apparatus, much less average

  17. Some Evolutionary Tendencies of Neotropical Primates

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    Defler Thomas

    2009-12-01

    Full Text Available

    Abstract

    The evolution of neotropical primates has occurred isolated from other primates of the world so that there is a distinct evolutionary history. There are various characteristics of neotropical primates (Platyrrhini that are quite distinct from those of the Old World (Catarrhini, including the dental formula, the position of cranial plates, the anatomy of the auditory apparatus, average body weights much less, much less terrestrial adaptation, prehensile tails for some, and conservative phenotypes. Additionally monogamous forms of platyrrhini share a tendency for rapid chromosome evolution with one monogamous group of catarrhines. The phyletic history of the platyrrhine monkeys seems to contrast with that of the catarrhine inasmuch as there was a very early division of the New World monkeys into groups that exist today, whereas the appearance of Old World primate family groups seemed to have happened much more recently in the Plio-Pleistocene. Some of these tendencies can be explained hypothetically, looking at ecological characteristics suggested for the new continent while other tendencies are perhaps the result of random evolutionary pathways taken during the course of evolution. Nevertheless there is still much work to do to be able to recognize the singularities of the Platyrrines

  18. Postcopulatory sexual selection influences baculum evolution in primates and carnivores

    Science.gov (United States)

    Brindle, Matilda

    2016-01-01

    The extreme morphological variability of the baculum across mammals is thought to be the result of sexual selection (particularly, high levels of postcopulatory selection). However, the evolutionary trajectory of the mammalian baculum is little studied and evidence for the adaptive function of the baculum has so far been elusive. Here, we use Markov chain Monte Carlo methods implemented in a Bayesian phylogenetic framework to reconstruct baculum evolution across the mammalian class and investigate the rate of baculum length evolution within the primate order. We then test the effects of testes mass (postcopulatory sexual selection), polygamy, seasonal breeding and intromission duration on the baculum in primates and carnivores. The ancestral mammal did not have a baculum, but both ancestral primates and carnivores did. No relationship was found between testes mass and baculum length in either primates or carnivores. Intromission duration correlated with baculum presence over the course of primate evolution, and prolonged intromission predicts significantly longer bacula in extant primates and carnivores. Both polygamous and seasonal breeding systems predict significantly longer bacula in primates. These results suggest the baculum plays an important role in facilitating reproductive strategies in populations with high levels of postcopulatory sexual selection. PMID:27974519

  19. A comparative neurological approach to emotional expressions in primate vocalizations.

    Science.gov (United States)

    Gruber, Thibaud; Grandjean, Didier

    2017-02-01

    Different approaches from different research domains have crystallized debate over primate emotional processing and vocalizations in recent decades. On one side, researchers disagree about whether emotional states or processes in animals truly compare to those in humans. On the other, a long-held assumption is that primate vocalizations are innate communicative signals over which nonhuman primates have limited control and a mirror of the emotional state of the individuals producing them, despite growing evidence of intentional production for some vocalizations. Our goal is to connect both sides of the discussion in deciphering how the emotional content of primate calls compares with emotional vocal signals in humans. We focus particularly on neural bases of primate emotions and vocalizations to identify cerebral structures underlying emotion, vocal production, and comprehension in primates, and discuss whether particular structures or neuronal networks solely evolved for specific functions in the human brain. Finally, we propose a model to classify emotional vocalizations in primates according to four dimensions (learning, control, emotional, meaning) to allow comparing calls across species.

  20. Laser-induced primate glaucoma. II. Histopathology.

    Science.gov (United States)

    Radius, R L; Pederson, J E

    1984-11-01

    A sustained, moderate pressure elevation was produced in 15 nonhuman primate eyes by application of laser energy to the trabecular meshwork. By light and electron microscopy, the trabecular beams were blunted, and scattered synechiae were present. Backward bowing of the lamina cribrosa, partial loss of the myelin sheath surrounding axonal segments just posterior to the lamina, and diffuse axonal loss involving the entire nerve cross section were noted. A quantitative analysis of this axonal loss revealed that eyes with moderate nerve head damage (cup-disc ratio, 0.6 to 0.8) had only 38% to 69% of the expected normal axonal count. The eyes with nearly total cupping (cup-disc ratio, 0.9 to 1.0) maintained between 10% and 36% of the normal axonal count. The disc changes in these experimental eyes are similar to those previously described in human eyes with glaucoma.

  1. Mediodorsal thalamus and cognition in nonhuman primates

    Directory of Open Access Journals (Sweden)

    Mark G Baxter

    2013-08-01

    Full Text Available Several recent studies in nonhuman primates have provided new insights into the role of the medial thalamus in different aspects of cognitive function. The mediodorsal nucleus of the thalamus (MD, by virtue of its connectivity with the frontal cortex, has been implicated in an array of cognitive functions. Rather than serving as an engine or relay for the prefrontal cortex, this area seems to be more specifically involved in regulating plasticity and flexibility of prefrontal-dependent cognitive functions. Focal damage to MD may also exacerbate the effects of damage to other subcortical relays. Thus a wide range of distributed circuits and cognitive functions may be disrupted from focal damage within the medial thalamus (for example as a consequence of stroke or brain injury. Conversely, this region may make an interesting target for neuromodulation of cognitive function via deep brain stimulation or related methods, in conditions associated with dysfunction of these neural circuits.

  2. Environmental enrichment for primates in laboratories

    Science.gov (United States)

    Buchanan-Smith, H. M.

    2010-06-01

    Environmental enrichment is a critical component of Refinement, one of the 3Rs underlying humane experimentation on animals. In this paper I discuss why primates housed in laboratories, which often have constraints of space and study protocols, are a special case for enrichment. I outline a framework for categorising the different types of enrichment, using the marmoset as a case study, and summarise the methods used to determine what animals want/prefer. I briefly review the arguments that enrichment does not negatively affect experimental outcomes. Finally I focus on complexity and novelty, choice and control, the underlying features of enrichment that makes it successful, and how combined with a thorough understanding of natural history we can put effective enrichment into practice in laboratories. Throughout the paper I emphasise the need to evaluate enrichment to ensure it is having the desired effect.

  3. Fast evolution of growth hormone receptor in primates and ruminants

    Institute of Scientific and Technical Information of China (English)

    HOU Zhenfang; LI Ying; ZHANG Yaping

    2005-01-01

    Pituitary growth hormone (GH) evolves very slowly in most of mammals, but the evolutionary rates appear to have increased markedly on two occasions during the evolution of primates and ruminants. To investigate the evolutionary pattern of growth hormone receptor (GHR), we sequenced the extracellular domain of GHR genes from four primate species. Our results suggested that GHR in mammal also shows an episodic evolutionary pattern, which is consistent with that observed in pituitary growth hormone. Further analysis suggested that this pattern of rapid evolution observed in primates and ruminants is likely the result of coevolution between pituitary growth hormone and its receptor.

  4. Neurobiological roots of language in primate audition: common computational properties.

    Science.gov (United States)

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L; Rauschecker, Josef P

    2015-03-01

    Here, we present a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics, including sentence and discourse processing, can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions.

  5. Transgenic nonhuman primates for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Chan Anthony WS

    2004-06-01

    Full Text Available Abstract Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD, Parkinson's disease (PD and Huntington's disease (HD have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which

  6. Pathological rate matrices: from primates to pathogens

    Directory of Open Access Journals (Sweden)

    Knight Rob

    2008-12-01

    Full Text Available Abstract Background Continuous-time Markov models allow flexible, parametrically succinct descriptions of sequence divergence. Non-reversible forms of these models are more biologically realistic but are challenging to develop. The instantaneous rate matrices defined for these models are typically transformed into substitution probability matrices using a matrix exponentiation algorithm that employs eigendecomposition, but this algorithm has characteristic vulnerabilities that lead to significant errors when a rate matrix possesses certain 'pathological' properties. Here we tested whether pathological rate matrices exist in nature, and consider the suitability of different algorithms to their computation. Results We used concatenated protein coding gene alignments from microbial genomes, primate genomes and independent intron alignments from primate genomes. The Taylor series expansion and eigendecomposition matrix exponentiation algorithms were compared to the less widely employed, but more robust, Padé with scaling and squaring algorithm for nucleotide, dinucleotide, codon and trinucleotide rate matrices. Pathological dinucleotide and trinucleotide matrices were evident in the microbial data set, affecting the eigendecomposition and Taylor algorithms respectively. Even using a conservative estimate of matrix error (occurrence of an invalid probability, both Taylor and eigendecomposition algorithms exhibited substantial error rates: ~100% of all exonic trinucleotide matrices were pathological to the Taylor algorithm while ~10% of codon positions 1 and 2 dinucleotide matrices and intronic trinucleotide matrices, and ~30% of codon matrices were pathological to eigendecomposition. The majority of Taylor algorithm errors derived from occurrence of multiple unobserved states. A small number of negative probabilities were detected from the Pad�� algorithm on trinucleotide matrices that were attributable to machine precision. Although the Pad

  7. RADIATION DOSE TO HUMAN AND NON-HUMAN BIOTA IN THE REPUBLIC OF KOREA RESULTING FROM THE FUKUSHIMA NUCLEAR ACCIDENT

    Directory of Open Access Journals (Sweden)

    DONG-KWON KEUM

    2013-02-01

    Full Text Available This paper describes the radiation doses to human and non-human biota in the Republic of Korea, as a result of the Fukushima nuclear accident. By using the measured airborne activity and ground deposition, the effective and thyroid doses of five human age groups (infant, 5 years, 10 years, 15 years and adult were estimated by the ECOSYS code, and the whole body absorbed dose rate of the eight Korean reference animals and plants (RAPs was estimated by the K-BIOTA (the Korean computer code to assess the risk of radioactivity to wildlife. The first-year effective and thyroid human doses ranged from 5.7E-5 mSv in the infant group to 2.0E-4 mSv in the 5 years group, and from 5.0E-4 mSv in the infant group to 3.4E-3 mSv in the 5 years group, respectively. The life-time (70 years effective and thyroid human doses ranged from 1.5E-4 mSv in the infant group to 3.0E-4 mSv in the 5 years group, and from 6.0E-4 mSv in the infant group to 3.5E-3 mSv in the 5 years group, respectively. The estimated maximum whole body absorbed dose rate to the Korean RAPs was 6.7E-7 mGy/d for a snake living in soil (terrestrial biota, and 2.0E-5 mGy/d for freshwater fish (aquatic biota, both of which were far less than the generic dose criteria to protect biota from ionizing radiation. Also, the screening level assessment for ERICA's (Environmental Risks from Ionizing Contaminants: Assessments and management limiting organisms showed that the risk quotient (RQ for the estimated maximum soil and water activity was significantly less than unity for both the terrestrial and freshwater organisms. Conclusively, the radiological risk of the radioactivity released into the environment by the Fukushima nuclear accident to the public and the non-human biota in the republic of Korea is considered negligible.

  8. The Females and the Non-Humans in Julie Taymor’s The Tempest

    Directory of Open Access Journals (Sweden)

    Mori Yukiko

    2015-12-01

    Full Text Available In Julie Taymor’s film version of Shakespeare’s The Tempest (2010, Prospero is changed into a female, Prospera. As almost all the original lines and plots are retained, the film would appear to be a ‘straight’ film version of Shakespeare. However, changing the sex of the main character sheds a new light on the original play and proves the film to be an inspiring adaptation. By examining the relationship between the female characters (Prospera, Miranda and the non-humans (Caliban, Ariel in the film, this paper will show how deeply sexuality is related to the power struggle and the final reconciliation.

  9. Use of non-human DNA analysis in forensic science: a mini review.

    Science.gov (United States)

    Iyengar, Arati; Hadi, Sibte

    2014-01-01

    Analysis of non-human DNA in forensic science, first reported about two decades ago, is now commonplace. Results have been used as evidence in court in a variety of cases ranging from abduction and murder to patent infringement and dog attack. DNA from diverse species, including commonly encountered pets such as dogs and cats, to plants, viruses and bacteria has been used and the sheer potential offered by such analyses has been proven. In this review, using case examples throughout, we detail the considerable literature in this field.

  10. Fukushima nuclear accident: preliminary assessment of the risks to non-human biota.

    Science.gov (United States)

    Aliyu, Abubakar Sadiq; Ramli, Ahmad Termizi; Garba, Nuraddeen Nasiru; Saleh, Muneer Aziz; Gabdo, Hamman Tukur; Liman, Muhammad Sanusi

    2015-02-01

    This study assesses the 'radio-ecological' impacts of Fukushima nuclear accident on non-human biota using the ERICA Tool, which adopts an internationally verified methodology. The paper estimates the impacts of the accident on terrestrial and marine biota based on the environmental data reported in literature for Japan, China, South Korea and the USA. Discernible impacts have been detected in the marine biota around Fukushima Daiichi nuclear power plant. This study confirms that the Fukushima accident had caused heavier damage to marine bionts compared with terrestrial flora and fauna, in Japan.

  11. The brain's router: a cortical network model of serial processing in the primate brain.

    Science.gov (United States)

    Zylberberg, Ariel; Fernández Slezak, Diego; Roelfsema, Pieter R; Dehaene, Stanislas; Sigman, Mariano

    2010-04-29

    The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality of operations (100-500 ms per step). A limit on parallel processing is demonstrated in experimental setups such as the psychological refractory period (PRP) and the attentional blink (AB) in which the processing of an element either significantly delays (PRP) or impedes conscious access (AB) of a second, rapidly presented element. Here we present a spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a "router" network capable of flexibly interconnecting processors and rapidly changing its configuration from one task to another. Simulations show that, when presented with dual-task stimuli, the network exhibits parallel processing at peripheral sensory levels, a memory buffer capable of keeping the result of sensory processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck. The network captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions, and establishes concrete predictions on neuronal dynamics during dual-task experiments in humans and non-human primates.

  12. Serotonergic, Brain Volume and Attentional Correlates of Trait Anxiety in Primates

    Science.gov (United States)

    Mikheenko, Yevheniia; Shiba, Yoshiro; Sawiak, Stephen; Braesicke, Katrin; Cockcroft, Gemma; Clarke, Hannah; Roberts, Angela C

    2015-01-01

    Trait anxiety is a risk factor for the development and maintenance of affective disorders, and insights into the underlying brain mechanisms are vital for improving treatment and prevention strategies. Translational studies in non-human primates, where targeted neurochemical and genetic manipulations can be made, are critical in view of their close neuroanatomical similarity to humans in brain regions implicated in trait anxiety. Thus, we characterised the serotonergic and regional brain volume correlates of trait-like anxiety in the marmoset monkey. Low- and high-anxious animals were identified by behavioral responses to a human intruder (HI) that are known to be sensitive to anxiolytic drug treatment. Extracellular serotonin levels within the amygdala were measured with in vivo microdialysis, at baseline and in response to challenge with the selective serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by structural magnetic resonance imaging. Anxious individuals showed persistent, long-term fearful responses to both a HI and a model snake, alongside sustained attention (vigilance) to novel cues in a context associated with unpredictable threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin levels, and smaller volumes in a closely connected prefrontal region, the dorsal anterior cingulate cortex. These findings highlight behavioral and neural similarities between trait-like anxiety in marmosets and humans, and set the stage for further investigation of the processes contributing to vulnerability and resilience to affective disorders. PMID:25586542

  13. Tool use in urban populations of capuchin monkeys Sapajus spp. (Primates: Cebidae

    Directory of Open Access Journals (Sweden)

    Lucas M. Aguiar

    2014-10-01

    Full Text Available Capuchin monkeys, Sapajus Kerr, 1792, are known for their flexible behavior, including tool use, and their ability to survive in urban forests. We observed capuchin juveniles using wood as hammer and anvil and different materials as sponges (four tool-use events in two geographically distinct urban populations in Brazil, in 2012: two in Goiânia, Central Brazil and two in Foz do Iguaçu, Southern Brazil. In Goiânia, a male used a detached tree branch as a hammer and a buttress root as an anvil to pound a seed of Terminalia Linnaeus. Another male used a small branch with leaves as a dipping tool to access water inside a tree trunk hole. In Foz do Iguaçu, the capuchins used a small branch and a piece of bread to obtain water by dipping them into tree trunk holes. This latter event might be interpreted as a case of self-control, with a familiar food item used as a tool to reach a resource that is difficult to access otherwise. Our observations contribute to the knowledge on the tool-kit of capuchins and we propose that these urban populations should be conserved for scientific evaluations of behavioral flexibility in non-human primates.

  14. A precise and minimally invasive approach to optogenetics in the awake primate

    Science.gov (United States)

    Nassi, Jonathan J.; Cetin, Ali H.; Roe, Anna W.; Callaway, Edward M.; Deisseroth, Karl; Reynolds, John H.

    2013-03-01

    Optogenetics has proven to be a powerful tool for understanding the function of specific cell types and circuits within the central nervous system and establishing a causal link between their activity and behavior. Its application in non-human primates has been slow to develop. One challenge has been the damage caused by transdural delivery of viruses and light to the brain. Here, we report optogenetic activation of neuronal responses in the alert and behaving monkey after replacement of the native dura with a transparent artificial dura. This approach enables the use of fine glass micropipettes to inject virus with minimal damage and transdural illumination, obviating the damage that would otherwise occur as a result of lowering optical fibers into the brain. It also permits visualization of the underlying cortical micro-vasculature, which has proven to be helpful in targeting electrodes and laser illumination to the virus location. This approach promises to greatly assist in the dissection of cortical circuits underlying visual perception and behavior.

  15. To what extent can human and non-human radiation protection frameworks be integrated?

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, C.; Stark, Karolina [Stockholm University (Sweden); Beaugelin-Seiller, Karine; Hinton, Thomas [Institut de radioprotection et de surete nucleaire - IRSN (France); Beresford, Nicholas A. [Centre for Ecology and Hydrology - CEH (United Kingdom); Brown, Justin; Dowdall, Mark; Hosseini, Ali; Liland, Astrid [Norwegian Radiation Protection Authority - NRPA (Norway); Mora, Juan Carlos; Real, Almudena; Robles, Beatriz [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas - CIEMAT (Spain); Oughton, Deborah [Norwegian University of Life Sciences - UMB (Norway); Steiner, Martin [Federal Office for Radiation Protection - BfS (Germany); Sweeck, Lieve; Vives I Batlle, Jordi [Belgian Nuclear Research Centre SCK-CEN (Belgium)

    2014-07-01

    The first radiation protection frameworks were initiated in the early 20. century and focused on the protection of humans. Protection frameworks for non-human species were developed later, based on the human protection system as well as that used to protect the environment from adverse effects of chemicals. These two radiation protection frameworks have to some degree developed quite separately from each other over the last few decades, and it is a source of debate as to what extent the integration of the two is possible. This presentation critically reviews some of the key aspects of integrating human and non-human assessment frameworks, including both conceptual and practical issues, and focuses on five main topics: 1) the conceptual consideration of humans as part of ecosystems, rather than a separate entity; 2) the consistency and potential harmonisation of underlying data and transfer model parameters; 3) consideration of different life stages and life histories in radiation protection and the implications for exposure, dose and effects; 4) calculation of doses, including modelling approaches, spatial and temporal variability and biokinetic modelling; and 5) benchmarks and screening values. Similarities and differences between the two existing frameworks are highlighted and the feasibility of integrating the two discussed. Our recommendations on how to further integrate, where achievable and warranted, are given. Document available in abstract form only. (authors)

  16. Brain size and ecology in small mammals and primates.

    OpenAIRE

    1980-01-01

    Comparisons of brain-body size relationships within small mammal and primate families reveal intergeneric differences related to diet and foraging strategy. These same associations between relative brain size and ecology are also evident among interfamily comparisons.

  17. Comparative triceps surae morphology in primates: a review.

    Science.gov (United States)

    Hanna, Jandy B; Schmitt, Daniel

    2011-01-01

    Primate locomotor evolution, particularly the evolution of bipedalism, is often examined through morphological studies. Many of these studies have examined the uniqueness of the primate forelimb, and others have examined the primate hip and thigh. Few data exist, however, regarding the myology and function of the leg muscles, even though the ankle plantar flexors are highly important during human bipedalism. In this paper, we draw together data on the fiber type and muscle mass variation in the ankle plantar flexors of primates and make comparisons to other mammals. The data suggest that great apes, atelines, and lorisines exhibit similarity in the mass distribution of the triceps surae. We conclude that variation in triceps surae may be related to the shared locomotor mode exhibited by these groups and that triceps surae morphology, which approaches that of humans, may be related to frequent use of semiplantigrade locomotion and vertical climbing.

  18. Emergent Patterns of Social Affiliation in Primates, a Model

    NARCIS (Netherlands)

    Puga-Gonzalez, Ivan; Hildenbrandt, Hanno; Hemelrijk, Charlotte K.

    2009-01-01

    Many patterns of affiliative behaviour have been described for primates, for instance: reciprocation and exchange of grooming, grooming others of similar rank, reconciliation of fights, and preferential reconciliation with more valuable partners. For these patterns several functions and underlying c

  19. Comparative Triceps Surae Morphology in Primates: A Review

    Directory of Open Access Journals (Sweden)

    Jandy B. Hanna

    2011-01-01

    Full Text Available Primate locomotor evolution, particularly the evolution of bipedalism, is often examined through morphological studies. Many of these studies have examined the uniqueness of the primate forelimb, and others have examined the primate hip and thigh. Few data exist, however, regarding the myology and function of the leg muscles, even though the ankle plantar flexors are highly important during human bipedalism. In this paper, we draw together data on the fiber type and muscle mass variation in the ankle plantar flexors of primates and make comparisons to other mammals. The data suggest that great apes, atelines, and lorisines exhibit similarity in the mass distribution of the triceps surae. We conclude that variation in triceps surae may be related to the shared locomotor mode exhibited by these groups and that triceps surae morphology, which approaches that of humans, may be related to frequent use of semiplantigrade locomotion and vertical climbing.

  20. Revisiting vocal perception in non-human animals: a review of vowel discrimination, speaker voice recognition, and speaker normalization

    Directory of Open Access Journals (Sweden)

    Buddhamas eKriengwatana

    2015-01-01

    Full Text Available The extent to which human speech perception evolved by taking advantage of predispositions and pre-existing features of vertebrate auditory and cognitive systems remains a central question in the evolution of speech. This paper reviews asymmetries in vowel perception, speaker voice recognition, and speaker normalization in non-human animals – topics that have not been thoroughly discussed in relation to the abilities of non-human animals, but are nonetheless important aspects of vocal perception. Throughout this paper we demonstrate that addressing these issues in non-human animals is relevant and worthwhile because many non-human animals must deal with similar issues in their natural environment. That is, they must also discriminate between similar-sounding vocalizations, determine signaler identity from vocalizations, and resolve signaler-dependent variation in vocalizations from conspecifics. Overall, we find that, although plausible, the current evidence is insufficiently strong to conclude that directional asymmetries in vowel perception are specific to humans, or that non-human animals can use voice characteristics to recognize human individuals. However, we do find some indication that non-human animals can normalize speaker differences. Accordingly, we identify avenues for future research that would greatly improve and advance our understanding of these topics.

  1. Feeding on Phytoestrogens: Implications of Estrogenic Plants for Primate Ecology

    OpenAIRE

    Wasserman, Michael David

    2011-01-01

    As most primates depend heavily on plant foods, the chemical composition of edible plant parts, both nutritional and detrimental, are of key importance in understanding primate ecology and evolution. One class of plant compounds of strong current interest due to their potential ability to alter the fertility, fecundity, and survival of both males and females are phytoestrogens. These plant compounds mimic the activity of vertebrate estrogens mainly through binding with the estrogen receptor...

  2. Towards Transgenic Primates: What can we learn from mouse genetics?

    Institute of Scientific and Technical Information of China (English)

    KUANG Hui; WANG Phillip L.; TSIEN Joe Z.

    2009-01-01

    Considering the great physiological and behavioral similarities with humans, monkeys represent the ideal models not only for the study of complex cognitive behavior but also for the precUnical research and development of novel therapeutics for treating human diseases. Various powerful genetic tech-nologies initially developed for making mouse models are being explored for generating transgenic primate models. We review the latest genetic engineering technologies and discuss the potentials and limitations for systematic production of transgenic primates.

  3. Euarchontan Opsin Variation Brings New Focus to Primate Origins

    OpenAIRE

    Melin, Amanda D.; Wells, Konstans; Moritz, Gillian L.; Kistler, Logan; Orkin, Joseph D.; Timm, Robert M.; Bernard, Henry; Lakim, Maklarin B.; Perry, George H.; Kawamura, Shoji; Dominy, Nathaniel J.

    2016-01-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders...

  4. The evolution of primate general and cultural intelligence.

    Science.gov (United States)

    Reader, Simon M; Hager, Yfke; Laland, Kevin N

    2011-04-12

    There are consistent individual differences in human intelligence, attributable to a single 'general intelligence' factor, g. The evolutionary basis of g and its links to social learning and culture remain controversial. Conflicting hypotheses regard primate cognition as divided into specialized, independently evolving modules versus a single general process. To assess how processes underlying culture relate to one another and other cognitive capacities, we compiled ecologically relevant cognitive measures from multiple domains, namely reported incidences of behavioural innovation, social learning, tool use, extractive foraging and tactical deception, in 62 primate species. All exhibited strong positive associations in principal component and factor analyses, after statistically controlling for multiple potential confounds. This highly correlated composite of cognitive traits suggests social, technical and ecological abilities have coevolved in primates, indicative of an across-species general intelligence that includes elements of cultural intelligence. Our composite species-level measure of general intelligence, 'primate g(S)', covaried with both brain volume and captive learning performance measures. Our findings question the independence of cognitive traits and do not support 'massive modularity' in primate cognition, nor an exclusively social model of primate intelligence. High general intelligence has independently evolved at least four times, with convergent evolution in capuchins, baboons, macaques and great apes.

  5. Euarchontan Opsin Variation Brings New Focus to Primate Origins.

    Science.gov (United States)

    Melin, Amanda D; Wells, Konstans; Moritz, Gillian L; Kistler, Logan; Orkin, Joseph D; Timm, Robert M; Bernard, Henry; Lakim, Maklarin B; Perry, George H; Kawamura, Shoji; Dominy, Nathaniel J

    2016-04-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination.

  6. Afrotarsius chatrathi, first tarsiiform primate (? Tarsiidae) from Africa

    Science.gov (United States)

    Simons, E.L.; Bown, T.M.

    1985-01-01

    Tarsiiform primates have long been regarded as a Laurasian group, with an extensive fossil record in the Eocene of North America and Europe1-4 and two important but less well-known records from Asia5,6. The only living genus is Tarsius (Tarsiidae), whereas all of the fossil tarsier-like primates are usually placed in the extinct family Omomyidae3. We now report the discovery of Afrotarsius chatrathi from early Oligocene rocks of Fayum Province, Egypt. This is the first known tarsiiform primate from Africa. Compared with fossil primates, the molar tooth morphology of this diminutive prosimian is most similar to that of the European Eocene microchoerine Pseudoloris; however, the closest similarity is to the molars of Tarsius. Because the phylogenetic relationships among living Tarsius and the omomyids remain unclear7,8 and because of the fragmentary nature of the only known specimen of this new primate, allocation of Afrotarsius to either Omomyidae or Tarsiidae is necessarily provisional. As we believe that its molar teeth are more like those of Tarsius than of any omomyids (including Pseudoloris), we tentatively assign the new genus to the extant family Tarsiidae as its only known fossil representative. Recovery of a Tarsius-like primate from Africa suggests that it or its ancestors might have been immigrants from Europe, may have been derived from an unknown Asian stock related to the ancestry of Tarsius, or may have originated in Africa. ?? 1985 Nature Publishing Group.

  7. Diversity, habitat preferences, and conservation of the primates of Southern Assam, India: The story of a primate paradise

    Directory of Open Access Journals (Sweden)

    Muhammed Khairujjaman Mazumder

    2014-12-01

    Full Text Available The southern part of Assam in India, a part of the Indo-Burma Biodiversity hotspot, harbors a myriad number of wild plant and animal species. Although there is only one protected area, the Barail Wildlife Sanctuary (Cachar district and a few reserve forests (RFs, there are as many as eight primates inhabiting the region – a diversity hardly found elsewhere. In addition to the protected area and RFs, tea gardens and secondary forests also serve as habitats for animals. The border areas of the region with the states of Manipur, Mizoram, Meghalaya, and Tripura are among the most important abodes of these primates. Unfortunately, these primates are under constant threat from multiple sources. The present article provides an extensive survey of the available literature on the primates of southern Assam with reference to their distribution, habitat preferences, threats, and conservation. Additionally, data from field observations of the author are also presented.

  8. What is the optimal anthropoid primate diet?

    CERN Document Server

    Dehmelt, H

    2001-01-01

    Following Socrates' advice "You should learn all you can from those who know. Everyone should watch himself throughout his life, and notice what sort of meat and drink and what form of exercise suit his constitution, and he should regulate them in order to enjoy good health." Based on biological, chemical and physical considerations I have attempted to synthesize guide lines for an optimal diet from the vast literature. For an offshoot of the primate line it may be wise not to stray too far from the line's surprisingly uniform predominantly frugi- and herbi-vorous diet that is only lightly supplemented by hunted small mammals, eggs, nuts, insects, etc. By dry weight raw wild fruit contains fats, proteins, carbohydrates, digested and undigested fiber in the approximate proportions 5 : 7 : 14 : 17 : 17. The fat component contains both essential fatty acids, about 23% linoleic and 16% alpha-linolenic, the latter severely lacking in Western diets. The practical problem is how to as best as possible, but not relig...

  9. Instinct(ive) play behaviour in human and non-human players

    DEFF Research Database (Denmark)

    Wirman, Hanna; Jørgensen, Ida Kathrine Hammeleff

    in human play? What kind of definition of ‘instinctual’ is meaningful for the study of games and play? Finally, how to design for instinctual or for non-instinctual play? While many such questions remain out of the reach of a humanist or a design researcher, this paper aims to focus on one single aspect......Instinctive stands in opposition to thoughtful. It is free from causal reasoning and deductive logic that bases on knowledge from past experience (Garrett 1997). Acknowledging how little is confirmed about the origins, importance or evolution of play in humans and non-humans (e.g. Burghardt 2005......), the part of instinctual also remains a mystery. In Wirman’s recent studies (e.g. Wirman 2015), however, we can recognise a human tendency to see ‘instinctive’ in animal behaviour while ‘play’ substitutes it in categorising human actions. This poses intriguing questions for multispecies game and play...

  10. Comparison of whole genome sequences from human and non-human Escherichia coli O26 strains

    Directory of Open Access Journals (Sweden)

    Keri N Norman

    2015-03-01

    Full Text Available Shiga toxin-producing Escherichia coli (STEC O26 is the second leading E. coli serogroup responsible for human illness outbreaks behind E. coli O157:H7. Recent outbreaks have been linked to emerging pathogenic O26:H11 strains harboring stx2 only. Cattle have been recognized as an important reservoir of O26 strains harboring stx1; however the reservoir of these emerging stx2 strains is unknown. The objective of this study was to identify nucleotide polymorphisms in human and cattle-derived strains in order to compare differences in polymorphism derived genotypes and virulence gene profiles between the two host species. Whole genome sequencing was performed on 182 epidemiologically unrelated O26 strains, including 109 human-derived strains and 73 non-human-derived strains. A panel of 289 O26 strains (241 STEC and 48 non-STEC was subsequently genotyped using a set of 283 polymorphisms identified by whole genome sequencing, resulting in 64 unique genotypes. Phylogenetic analyses identified seven clusters within the O26 strains. The seven clusters did not distinguish between isolates originating from humans or cattle; however, clusters did correspond with particular virulence gene profiles. Human and non-human-derived strains harboring stx1 clustered separately from strains harboring stx2, strains harboring eae, and non-STEC strains. Strains harboring stx2 were more closely related to non-STEC strains and strains harboring eae than to strains harboring stx1. The finding of human and cattle-derived strains with the same polymorphism derived genotypes and similar virulence gene profiles, provides evidence that similar strains are found in cattle and humans and transmission between the two species may occur.

  11. Led by the nose: Olfaction in primate feeding ecology.

    Science.gov (United States)

    Nevo, Omer; Heymann, Eckhard W

    2015-01-01

    Olfaction, the sense of smell, was a latecomer to the systematic investigation of primate sensory ecology after long years in which it was considered to be of minor importance. This view shifted with the growing understanding of its role in social behavior and the accumulation of physiological studies demonstrating that the olfactory abilities of some primates are on a par with those of olfactory-dependent mammals such as dogs and rodents. Recent years have seen a proliferation of physiological, behavioral, anatomical, and genetic investigations of primate olfaction. These investigations have begun to shed light on the importance of olfaction in the process of food acquisition. However, integration of these works has been limited. It is therefore still difficult to pinpoint large-scale evolutionary scenarios, namely the functions that the sense of smell fulfills in primates' feeding ecology and the ecological niches that favor heavier reliance on olfaction. Here, we review available behavioral and physiological studies of primates in the field or captivity and try to elucidate how and when the sense of smell can help them acquire food.

  12. Grooming reciprocation among female primates: a meta-analysis.

    Science.gov (United States)

    Schino, Gabriele; Aureli, Filippo

    2008-02-23

    The theory of reciprocal altruism offers an explanation for the evolution of altruistic behaviours among unrelated animals. Among primates, grooming is one of the most common altruistic behaviours. Primates have been suggested to exchange grooming both for itself and for rank-related benefits. While previous meta-analyses have shown that they direct their grooming up the hierarchy and exchange it for agonistic support, no comprehensive evaluation of grooming reciprocation has been made. Here we report on a meta-analysis of grooming reciprocation among female primates based on 48 social groups belonging to 22 different species and 12 genera. The results of this meta-analysis showed that female primates groom preferentially those group mates that groom them most. To the extent allowed by the availability of kinship data, this result holds true when controlling for maternal kinship. These results, together with previous findings, suggest that primates are indeed able to exchange grooming both for itself and for different rank-related benefits.

  13. Male infanticide leads to social monogamy in primates.

    Science.gov (United States)

    Opie, Christopher; Atkinson, Quentin D; Dunbar, Robin I M; Shultz, Susanne

    2013-08-13

    Although common in birds, social monogamy, or pair-living, is rare among mammals because internal gestation and lactation in mammals makes it advantageous for males to seek additional mating opportunities. A number of hypotheses have been proposed to explain the evolution of social monogamy among mammals: as a male mate-guarding strategy, because of the benefits of biparental care, or as a defense against infanticidal males. However, comparative analyses have been unable to resolve the root causes of monogamy. Primates are unusual among mammals because monogamy has evolved independently in all of the major clades. Here we combine trait data across 230 primate species with a Bayesian likelihood framework to test for correlated evolution between monogamy and a range of traits to evaluate the competing hypotheses. We find evidence of correlated evolution between social monogamy and both female ranging patterns and biparental care, but the most compelling explanation for the appearance of monogamy is male infanticide. It is only the presence of infanticide that reliably increases the probability of a shift to social monogamy, whereas monogamy allows the secondary adoption of paternal care and is associated with a shift to discrete ranges. The origin of social monogamy in primates is best explained by long lactation periods caused by altriciality, making primate infants particularly vulnerable to infanticidal males. We show that biparental care shortens relative lactation length, thereby reducing infanticide risk and increasing reproductive rates. These phylogenetic analyses support a key role for infanticide in the social evolution of primates, and potentially, humans.

  14. Evolution of coding microsatellites in primate genomes.

    Science.gov (United States)

    Loire, Etienne; Higuet, Dominique; Netter, Pierre; Achaz, Guillaume

    2013-01-01

    Microsatellites (SSRs) are highly susceptible to expansions and contractions. When located in a coding sequence, the insertion or the deletion of a single unit for a mono-, di-, tetra-, or penta(nucleotide)-SSR creates a frameshift. As a consequence, one would expect to find only very few of these SSRs in coding sequences because of their strong deleterious potential. Unexpectedly, genomes contain many coding SSRs of all types. Here, we report on a study of their evolution in a phylogenetic context using the genomes of four primates: human, chimpanzee, orangutan, and macaque. In a set of 5,015 orthologous genes unambiguously aligned among the four species, we show that, except for tri- and hexa-SSRs, for which insertions and deletions are frequently observed, SSRs in coding regions evolve mainly by substitutions. We show that the rate of substitution in all types of coding SSRs is typically two times higher than in the rest of coding sequences. Additionally, we observe that although numerous coding SSRs are created and lost by substitutions in the lineages, their numbers remain constant. This last observation suggests that the coding SSRs have reached equilibrium. We hypothesize that this equilibrium involves a combination of mutation, drift, and selection. We thus estimated the fitness cost of mono-SSRs and show that it increases with the number of units. We finally show that the cost of coding mono-SSRs greatly varies from function to function, suggesting that the strength of the selection that acts against them can be correlated to gene functions.

  15. Gene transfer in rodents and primates as a new tool for modeling diseases in animals and assessing functions by in vivo imaging

    Energy Technology Data Exchange (ETDEWEB)

    Deglon, N. [Atomic Energy Commission (CEA), Dept. of Medical Research and MIRCen Program, 91 - Orsay (France)

    2006-07-01

    The identification of disease-causing genes in familial forms of neuro-degenerative disorders and the development of genetic models closely replicating human CNS pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions efficient delivery systems taking into account the specificity of the central nervous system are required to administer therapeutic candidates. In addition, there is a need to develop 1) genetic models in large animals that replicate late stages of the diseases and 2) imaging techniques suitable for longitudinal, quantitative and non-invasive evaluation of disease progression and the evaluation of new therapeutic strategies. Over the last few years, we have investigated the potential of lentiviral vectors as tool to model and treat CNS disorders. The use of lentiviral vectors to create animal model of these pathologies holds various advantages compared to classical transgenic approaches. Viral vectors are versatile, highly flexible tools to perform in vivo studies. Multiple genetic models can be created in a short period of time. High transduction efficiencies as well as robust and sustained trans-gene expression lead to the rapid appearance of functional and behavioral abnormalities and severe neuro-degeneration. Targeted injections in different brain areas can be used to investigate the regional specificity of the neuro-pathology and eliminate potential side effects associated with a widespread over-expression of the trans-gene. Finally, models can be established in different mammalian species including non-human primates, thereby providing an opportunity to assess complex behavioral changes and perform longitudinal follow-up of neuro-pathological alterations by imaging. We have demonstrated the proof of principle of this approach for Huntington's disease. We have shown that the intratriatal injection of lentiviral

  16. Primate-specific evolution of an LDLR enhancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-Fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

    2005-12-01

    Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.

  17. The Jaw Adductor Resultant and Estimated Bite Force in Primates

    Directory of Open Access Journals (Sweden)

    Jonathan M. G. Perry

    2011-01-01

    Full Text Available We reconstructed the jaw adductor resultant in 34 primate species using new data on muscle physiological cross-sectional area (PCSA and data on skull landmarks. Based on predictions by Greaves, the resultant should (1 cross the jaw at 30% of its length, (2 lie directly posterior to the last molar, and (3 incline more anteriorly in primates that need not resist large anteriorly-directed forces. We found that the resultant lies significantly posterior to its predicted location, is significantly posterior to the last molar, and is significantly more anteriorly inclined in folivores than in frugivores. Perhaps primates emphasize avoiding temporomandibular joint distraction and/or wide gapes at the expense of bite force. Our exploration of trends in the data revealed that estimated bite force varies with body mass (but not diet and is significantly greater in strepsirrhines than in anthropoids. This might be related to greater contribution from the balancing-side jaw adductors in anthropoids.

  18. Morphology of the shoulder muscles in Sapajus apella (Primates: Cebidae

    Directory of Open Access Journals (Sweden)

    Mariana Oliveira Lima

    2013-03-01

    Full Text Available The study of nonhuman primates has been very important, due to the similarities with the human species. Many animal species, especially primates, have been used in medical and biological researches. Sapajus apella is a species with usual and abundant incidence in the Southeastern Region. This paper aimed to study the stabilizing muscles of the shoulder in the tufted capuchin monkey and compare them to those in human beings, with the purpose of providing information to anatomical and functional interpretations which will be useful for further studies on comparative anatomy. Four specimens of S. apella from the Human Anatomy Laboratory of Universidade Federal de Uberlandia were used. The specimens were prepared through dissection of the stabilizing muscles of the shoulder and preserved in formaldehyde solution. It was observed that the shoulder stabilizing muscles of the S. apella present morphological similarities, regarding origin and branching, with those found in human beings, as well as in other primates.

  19. Primate vocalization, gesture, and the evolution of human language.

    Science.gov (United States)

    Arbib, Michael A; Liebal, Katja; Pika, Simone

    2008-12-01

    The performance of language is multimodal, not confined to speech. Review of monkey and ape communication demonstrates greater flexibility in the use of hands and body than for vocalization. Nonetheless, the gestural repertoire of any group of nonhuman primates is small compared with the vocabulary of any human language and thus, presumably, of the transitional form called protolanguage. We argue that it was the coupling of gestural communication with enhanced capacities for imitation that made possible the emergence of protosign to provide essential scaffolding for protospeech in the evolution of protolanguage. Similarly, we argue against a direct evolutionary path from nonhuman primate vocalization to human speech. The analysis refines aspects of the mirror system hypothesis on the role of the primate brain's mirror system for manual action in evolution of the human language-ready brain.

  20. Primate dental ecology: How teeth respond to the environment.

    Science.gov (United States)

    Cuozzo, Frank P; Ungar, Peter S; Sauther, Michelle L

    2012-06-01

    Teeth are central for the study of ecology, as teeth are at the direct interface between an organism and its environment. Recent years have witnessed a rapid growth in the use of teeth to understand a broad range of topics in living and fossil primate biology. This in part reflects new techniques for assessing ways in which teeth respond to, and interact with, an organism's environment. Long-term studies of wild primate populations that integrate dental analyses have also provided a new context for understanding primate interactions with their environments. These new techniques and long-term field studies have allowed the development of a new perspective-dental ecology. We define dental ecology as the broad study of how teeth respond to, or interact with, the environment. This includes identifying patterns of dental pathology and tooth use-wear, as they reflect feeding ecology, behavior, and habitat variation, including areas impacted by anthropogenic disturbance, and how dental development can reflect environmental change and/or stress. The dental ecology approach, built on collaboration between dental experts and ecologists, holds the potential to provide an important theoretical and practical framework for inferring ecology and behavior of fossil forms, for assessing environmental change in living populations, and for understanding ways in which habitat impacts primate growth and development. This symposium issue brings together experts on dental morphology, growth and development, tooth wear and health, primate ecology, and paleontology, to explore the broad application of dental ecology to questions of how living and fossil primates interact with their environments.

  1. Primate-Specific Evolution of an LDLR Enhancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

    2006-06-28

    Sequence changes in regulatory regions have often beeninvoked to explain phenotypic divergence among species, but molecularexamples of this have been difficult to obtain. In this study, weidentified an anthropoid primate specific sequence element thatcontributed to the regulatory evolution of the LDL receptor. Using acombination of close and distant species genomic sequence comparisonscoupled with in vivo and in vitro studies, we show that a functionalcholesterol-sensing sequence motif arose and was fixed within apre-existing enhancer in the common ancestor of anthropoid primates. Ourstudy demonstrates one molecular mechanism by which ancestral mammalianregulatory elements can evolve to perform new functions in the primatelineage leading to human.

  2. Fully human monoclonal antibody inhibitors of the neonatal Fc receptor (FcRn reduce circulating IgG in nonhuman primates

    Directory of Open Access Journals (Sweden)

    Andrew E Nixon

    2015-04-01

    Full Text Available The therapeutic management of antibody mediated autoimmune disease typically involves immunosuppressant and immunomodulatory strategies. However, perturbing the fundamental role of the neonatal Fc receptor (FcRn in salvaging IgG from lysosomal degradation provides a novel approach – depleting the body of pathogenic immunoglobulin by preventing IgG binding to FcRn and thereby increasing the rate of IgG catabolism. Herein, we describe the discovery and preclinical evaluation of fully human monoclonal IgG antibody inhibitors of FcRn. Using phage display, we identified several potent inhibitors of human FcRn in which binding to FcRn is pH independent, with over 1000-fold higher affinity for human FcRn than human IgG-Fc at pH 7.4. FcRn antagonism in vivo using a human-FcRn knock-in transgenic mouse model caused enhanced catabolism of exogenously administered human IgG. In non-human primates we observed reductions in endogenous circulating IgG of > 60% with no changes in albumin, IgM, or IgA. FcRn antagonism did not disrupt the ability of non-human primates to mount IgM/IgG primary and secondary immune responses. Interestingly, the therapeutic anti-FcRn antibodies had a short serum half-life but caused a prolonged reduction in IgG levels. This may be explained by the high affinity of the antibodies to FcRn at both acidic and neutral pH. These results provide important preclinical proof of concept data in support of FcRn antagonism as a novel approach to the treatment of antibody mediated autoimmune diseases.

  3. Panpsychism, pan-consciousness and the non-human turn: Rethinking being as conscious matter

    Directory of Open Access Journals (Sweden)

    Cornel du Toit

    2016-05-01

    Full Text Available It is not surprising that in a time of intensified ecological awareness a new appreciation of nature and the inanimate world arises. Two examples are panpsychism (the extension of consciousness to the cosmos and deep incarnation (the idea that God was not only incarnated in human form but also in the non-human world. Consciousness studies flourish and are related to nature, the animal world and inorganic nature. A metaphysics of consciousness emerges, of which panpsychism is a good example. Panpsychism or panconsciousness or speculative realism endows all matter with a form of consciousness, energy and experience. The consciousness question is increasingly linked to the quantum world, which offers some option in bridging mind and reality, consciousness and matter. In this regard Kauffman’s notion of ‘triad’ is referred to as well as the implied idea of cosmic mind. This is related to the notion of ‘deep incarnation’ as introduced by Gregersen. Some analogical links are made between panpsychism and deep incarnation.

  4. NON-HUMAN SPIRITS, INHUMAN SPIRITS: THE SUPERNATURE WORLD OF THE SURUWAHA FROM THE PURUS RIVER

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    Miguel Aparicio

    2015-12-01

    Full Text Available The Suruwaha, a group from the Purus River basin, Western Amazonia, that speaks an Arawan language, conceive beings inhabiting other regions of the cosmos as jadawasu, non-human - and even some of them as inhuman. These “spirits” have bodies with human appearance and are able to interact with humans’ bodies. The Suruwaha identify various supernatural beings profiles: kurimia, karuji, uhwamy, zamakusa - a panorama of multiplicity integrating homogeneity and difference. On the one hand there is a possible similarity with humans; on the other, a difference that enables constant unfolding (consequently raising confusion and incommensurability, danuzy. The descriptions of their bodies are recurrent, presenting them as subjects who develop a peculiar "physiology" which prevents them of being characterized as intangible or invisible. What exactly defines these beings is not, strictly, their "spiritual" condition, but their heterotopic condition: they are different from humans mainly because their place is constitutively other, not because their nature is different. “Heterotopy” is the trait that distinguishes them from the jadawa, inhabitants of the humanized space.

  5. Consciousness in humans and non-human animals: Recent advances and future directions.

    Directory of Open Access Journals (Sweden)

    Melanie eBoly

    2013-10-01

    Full Text Available This joint article reflects the authors’ personal views regarding noteworthy advances in the neuroscience of consciousness in the last ten years, and suggests what we feel may be promising future directions. It is based on a small conference at the Samoset Resort in Rockport, Maine, USA, in July of 2012, organized by the Mind Science Foundation of San Antonio, Texas. Here, we summarize recent advances in our understanding of subjectivity in humans and other animals, including empirical, applied, technical and conceptual insights. These include the evidence for the importance of fronto-parietal connectivity and of feedback processes, both of which enable information to travel across distant cortical areas effectively, as well as numerous dissociations between consciousness and cognitive functions, such as attention, in humans. In addition, we describe the development of mental imagery paradigms, which made it possible to identify covert awareness in non-responsive subjects. Non-human animal consciousness research has also witnessed substantial advances on the specific role of cortical areas and higher order thalamus for consciousness, thanks to important technological advances. In addition, much progress has been made in the understanding of non-vertebrate cognition relevant to possible conscious states. Finally, major advances have been made in theories of consciousness, and also in their comparison with the available evidence. Along with reviewing these findings, each author suggests future avenues for research in their field of investigation.

  6. Insights into an Optimization of Plasmodium vivax Sal-1 In Vitro Culture: The Aotus Primate Model.

    Science.gov (United States)

    Shaw-Saliba, Kathryn; Thomson-Luque, Richard; Obaldía, Nicanor; Nuñez, Marlon; Dutary, Sahir; Lim, Caeul; Barnes, Samantha; Kocken, Clemens H M; Duraisingh, Manoj T; Adams, John H; Pasini, Erica M

    2016-07-01

    Malaria is one of the most significant tropical diseases, and of the Plasmodium species that cause human malaria, P. vivax is the most geographically widespread. However, P. vivax remains a relatively neglected human parasite since research is typically limited to laboratories with direct access to parasite isolates from endemic field settings or from non-human primate models. This restricted research capacity is in large part due to the lack of a continuous P. vivax in vitro culture system, which has hampered the ability for experimental research needed to gain biological knowledge and develop new therapies. Consequently, efforts to establish a long-term P. vivax culture system are confounded by our poor knowledge of the preferred host cell and essential nutrients needed for in vitro propagation. Reliance on very heterogeneous P. vivax field isolates makes it difficult to benchmark parasite characteristics and further complicates development of a robust and reliable culture method. In an effort to eliminate parasite variability as a complication, we used a well-defined Aotus-adapted P. vivax Sal-1 strain to empirically evaluate different short-term in vitro culture conditions and compare them with previous reported attempts at P. vivax in vitro culture Most importantly, we suggest that reticulocyte enrichment methods affect invasion efficiency and we identify stabilized forms of nutrients that appear beneficial for parasite growth, indicating that P. vivax may be extremely sensitive to waste products. Leuko-depletion methods did not significantly affect parasite development. Formatting changes such as shaking and static cultures did not seem to have a major impact while; in contrast, the starting haematocrit affected both parasite invasion and growth. These results support the continued use of Aotus-adapted Sal-1 for development of P. vivax laboratory methods; however, further experiments are needed to optimize culture conditions to support long-term parasite

  7. A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

    Science.gov (United States)

    Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

    2016-11-10

    Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for

  8. Linking reward processing to behavioral output: motor and motivational integration in the primate subthalamic nucleus

    Directory of Open Access Journals (Sweden)

    Juan-Francisco eEspinosa-Parrilla

    2013-12-01

    Full Text Available The expectation and detection of motivationally relevant events is a major determinant of goal-directed behavior and there is a strong interest in the contribution of basal ganglia in the integration of motivational processes into behavioral output. Recent research has focused on the role of the subthalamic nucleus (STN in the motivational control of action, but it remains to be determined how information about reward is encoded in this nucleus. We recorded the activity of single neurons in the STN of two behaving monkeys to examine whether activity was influenced by the delivery of reward in an instrumental task, a Pavlovian stimulus-reward association, or outside of a task context. We confirmed preliminary findings indicating that STN neurons were sensitive not only to rewards obtained during task performance, but also to the expectation of reward when its delivery was delayed in time. Most of the modulations at the onset of reaching movement were combined with modulations following reward delivery, suggesting the convergence of signals related to the animal’s movement and its outcome in the same neurons. Some neurons were also influenced by the visuomotor contingencies of the task, i.e., target location and/or movement direction. In addition, modulations were observed under conditions where reward delivery was not contingent on an instrumental response, even in the absence of a reward predictive cue. Taken as a whole, these results demonstrate a potential contribution of the STN to motivational control of behavior in the non-human primate, although problems in distinguishing neuronal signals related to reward from those related to motor behavior should be considered. Characterizing the specificity of reward processing in the STN remains challenging and could have important implications for understanding the influence of this key component of basal ganglia circuitry on emotional and motivated behaviors under normal and pathological

  9. Validation of serological tests for the detection of antibodies against Treponema pallidum in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Sascha Knauf

    2015-03-01

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

  10. Validation of serological tests for the detection of antibodies against Treponema pallidum in nonhuman primates.

    Science.gov (United States)

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

    2015-03-01

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

  11. Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

    Science.gov (United States)

    Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

    2008-09-25

    Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

  12. Trypanosoma cruzi in Brazilian Amazonia: Lineages TCI and TCIIa in wild primates, Rhodnius spp. and in humans with Chagas disease associated with oral transmission.

    Science.gov (United States)

    Marcili, Arlei; Valente, Vera C; Valente, Sebastião A; Junqueira, Angela C V; da Silva, Flávia Maia; Pinto, Ana Yecê das Neves; Naiff, Roberto D; Campaner, Marta; Coura, José R; Camargo, Erney P; Miles, Michael A; Teixeira, Marta M G

    2009-04-01

    In this study, we provide phylogenetic and biogeographic evidence that the Trypanosoma cruzi lineages T. cruzi I (TCI) and T. cruzi IIa (TCIIa) circulate amongst