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Sample records for human primates elevation

  1. Captivity humanizes the primate microbiome.

    Science.gov (United States)

    Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

    2016-09-13

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

  2. Differential Mobility Spectrometry (DMS) Reveals the Elevation of Urinary Acetylcarnitine in Non-Human Primates (NHPs) Exposed to Radiation.

    Science.gov (United States)

    Vera, Nicholas B; Chen, Zhidan; Pannkuk, Evan; Laiakis, Evagelia C; Fornace, Albert J; Erion, Derek M; Coy, Stephen L; Pfefferkorn, Jeffrey A; Vouros, Paul

    2018-03-29

    Acetylcarnitine has been identified as one of several urinary biomarkers indicative of radiation exposure in adult rhesus macaque monkeys (non-human primates, NHPs). Previous work has demonstrated an up-regulated dose-response profile in a balanced male/female NHP cohort 1 . As a contribution toward the development of metabolomics-based radiation biodosimetry in human populations and other applications of acetylcarnitine screening, we have developed a quantitative, high-throughput method for the analysis of acetylcarnitine. We employed the Sciex SelexIon DMS-MS/MS QTRAP 5500 platform coupled to flow injection analysis (FIA), thereby allowing for fast analysis times of less than 0.5 minutes per injection with no chromatographic separation. Ethyl acetate is used as a DMS modifier to reduce matrix chemical background. We have measured NHP urinary acetylcarnitine from the male cohorts that were exposed to the following radiation levels: control, 2 Gy, 4 Gy, 6 Gy, 7 Gy and 10 Gy. Biological variability, along with calibration accuracy of the FIA-DMS-MS/MS method, indicate LOQ of 20 μM, with observed biological levels on the order of 600 μM and control levels near 10 μM. There is an apparent onset of intensified response in the transition from 6 Gy to 10 Gy. The results demonstrate that FIA-DMS-MS/MS is a rapid, quantitative technique that can be utilized for the analysis of urinary biomarker levels for radiation biodosimetry. This article is protected by copyright. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    John D. Short

    2017-08-01

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

  4. Perceptions of nonhuman primates in human-wildlife conflict scenarios.

    Science.gov (United States)

    Hill, Catherine M; Webber, Amanda D

    2010-09-01

    Nonhuman primates (referred to as primates in this study) are sometimes revered as gods, abhorred as evil spirits, killed for food because they damage crops, or butchered for sport. Primates' perceived similarity to humans places them in an anomalous position. While some human groups accept the idea that primates "straddle" the human-nonhuman boundary, for others this resemblance is a violation of the human-animal divide. In this study we use two case studies to explore how people's perceptions of primates are often influenced by these animals' apparent similarity to humans, creating expectations, founded within a "human morality" about how primates should interact with people. When animals transgress these social rules, they are measured against the same moral framework as humans. This has implications for how people view and respond to certain kinds of primate behaviors, their willingness to tolerate co-existence with primates and their likely support for primate conservation initiatives. 2010 Wiley-Liss, Inc.

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

    Science.gov (United States)

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

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

  6. Inversion variants in human and primate genomes.

    Science.gov (United States)

    Catacchio, Claudia Rita; Maggiolini, Flavia Angela Maria; D'Addabbo, Pietro; Bitonto, Miriana; Capozzi, Oronzo; Signorile, Martina Lepore; Miroballo, Mattia; Archidiacono, Nicoletta; Eichler, Evan E; Ventura, Mario; Antonacci, Francesca

    2018-05-18

    For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies. We identified a total of 156 putative inversions, between 103 kb and 91 Mb, corresponding to 136 human loci. Combining literature, sequence, and experimental analyses, we analyzed 109 of these loci and found 67 regions inverted in one or multiple primates, including 28 newly identified inversions. These events overlap with 81 human genes at their breakpoints, and seven correspond to sites of recurrent rearrangements associated with human disease. This work doubles the number of validated primate inversions larger than 100 kb, beyond what was previously documented. We identified 74 sites of errors, where the sequence has been assembled in the wrong orientation, in the reference genomes analyzed. Our data serve two purposes: First, we generated a map of evolutionary inversions in these genomes representing a resource for interrogating differences among these species at a functional level; second, we provide a list of misassembled regions in these primate genomes, involving over 300 Mb of DNA and 1978 human genes. Accurately annotating these regions in the genome references has immediate applications for evolutionary and biomedical studies on primates. © 2018 Catacchio et al.; Published by Cold Spring Harbor Laboratory Press.

  7. Microgravity Flight - Accommodating Non-Human Primates

    Science.gov (United States)

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

    1994-01-01

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

  8. Visuomotor cerebellum in human and nonhuman primates.

    Science.gov (United States)

    Voogd, Jan; Schraa-Tam, Caroline K L; van der Geest, Jos N; De Zeeuw, Chris I

    2012-06-01

    In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula-nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.

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

    Science.gov (United States)

    Weiss, Daniel J.; Santos, Laurie R.

    2006-01-01

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

  10. Male germline stem cells in non-human primates

    Directory of Open Access Journals (Sweden)

    S. Sharma

    2017-09-01

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

  11. Nutritional ecology of entomophagy in humans and other primates.

    Science.gov (United States)

    Raubenheimer, David; Rothman, Jessica M

    2013-01-01

    Entomophagy is widespread among nonhuman primates and is common among many human communities. However, the extent and patterns of entomophagy vary substantially both in humans and nonhuman primates. Here we synthesize the literature to examine why humans and other primates eat insects and what accounts for the variation in the extent to which they do so. Variation in the availability of insects is clearly important, but less understood is the role of nutrients in entomophagy. We apply a multidimensional analytical approach, the right-angled mixture triangle, to published data on the macronutrient compositions of insects to address this. Results showed that insects eaten by humans spanned a wide range of protein-to-fat ratios but were generally nutrient dense, whereas insects with high protein-to-fat ratios were eaten by nonhuman primates. Although suggestive, our survey exposes a need for additional, standardized, data.

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

    National Research Council Canada - National Science Library

    Dobie, Thomas

    2001-01-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

  14. Microgravity Flight: Accommodating Non-Human Primates

    Science.gov (United States)

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

    1995-01-01

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

  15. The well-being of laboratory non-human primates.

    Science.gov (United States)

    Baker, Kate C; Dettmer, Amanda M

    2017-01-01

    The well-being of non-human primates in captivity is of joint concern to scientists, veterinarians, colony managers, caretakers, and researchers working with non-human primates in biomedical research. With increased regulatory, accreditation, and research focus on optimizing the use of social housing for laboratory primates, as well as the advent of techniques to assess indices of chronic stress and related measures of well-being, there is no better time to present the most current advances in the field of non-human primate behavioral management. The collective body of research presented here was inspired in part by a 2014 symposium entitled, "Chronic Hormones and Demographic Variables: Center-Wide Studies on Non-Human Primate Well-Being" held at the American Society of Primatologists' 37th Annual Meeting in Decatur, GA. By aiming to target readership with scientific and/or management oversight of captive primate behavioral management programs, this special issue provides badly-needed guidance for implementing social housing programs in a research environment and leverages collaboration across multiple facilities to address key components of behavioral management, explore refinements in how well-being can be measured, and identify the interrelationships between varying indices. Am. J. Primatol. 79:e22520, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

    Science.gov (United States)

    Sengupta, Asmita; McConkey, Kim R; Radhakrishna, Sindhu

    2015-01-01

    Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

  17. Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

    Directory of Open Access Journals (Sweden)

    Asmita Sengupta

    Full Text Available Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

  18. The Non-Human Primate Experimental Glaucoma Model

    Science.gov (United States)

    Burgoyne, Claude F.

    2015-01-01

    The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic IOP elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model. PMID:26070984

  19. Why does multiple sclerosis only affect human primates?

    NARCIS (Netherlands)

    't Hart, Bert A.

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

  20. [Diversity and development of positional behavior in non-human primates].

    Science.gov (United States)

    Zhang, Jing; Qi, Xiao-Guang; Zhang, Kan; Zhang, Pei; Guo, Song-Tao; Wei, Wei; Li, Bao-Guo

    2012-10-01

    In long-term evolution, wildlife in general and primates in particular have formed specific patterns of behavior to adapt to a diverse variety of habitat environments. Current research on positional behavior in non-human primates has been found to explain a great deal about primate adaptability diversification, ecology, anatomy and evolution. Here, we summarize the noted classifications and differences in seasonal, site-specific and sex-age positional behaviors while also reviewing the development and status of non-human primate positional behavior research. This review is intended to provide reference for the future research of non-human primates and aid in further research on behavioral ecology of primates.

  1. Extensive diversity of intestinal trichomonads of non-human primates

    Czech Academy of Sciences Publication Activity Database

    Smejkalová, P.; Petrželková, Klára Judita; Pomajbíková, K.; Modrý, David; Čepička, I.

    2012-01-01

    Roč. 139, č. 1 (2012), s. 92-102 ISSN 0031-1820 R&D Projects: GA ČR GA206/09/0927 Institutional research plan: CEZ:AV0Z60930519; CEZ:AV0Z60220518 Keywords : trichomonads * Parabasalia * non-human primates * diversity * host specificity Subject RIV: EG - Zoology Impact factor: 2.355, year: 2012

  2. Differences in auditory timing between human and nonhuman primates

    NARCIS (Netherlands)

    Honing, H.; Merchant, H.

    2014-01-01

    The gradual audiomotor evolution hypothesis is proposed as an alternative interpretation to the auditory timing mechanisms discussed in Ackermann et al.'s article. This hypothesis accommodates the fact that the performance of nonhuman primates is comparable to humans in single-interval tasks (such

  3. Primate social attention: Species differences and effects of individual experience in humans, great apes, and macaques

    OpenAIRE

    Kano, Fumihiro; Shepherd, Stephen V.; Hirata, Satoshi; Call, Josep

    2018-01-01

    When viewing social scenes, humans and nonhuman primates focus on particular features, such as the models’ eyes, mouth, and action targets. Previous studies reported that such viewing patterns vary significantly across individuals in humans, and also across closely-related primate species. However, the nature of these individual and species differences remains unclear, particularly among nonhuman primates. In large samples of human and nonhuman primates, we examined species differences and th...

  4. Vaccines against viral hemorrhagic fevers: non-human primate models.

    Science.gov (United States)

    Carrion, Ricardo; Patterson, Jean L

    2011-06-01

    Viral hemorrhagic fevers are a group of disease syndromes caused by infection with certain RNA viruses. The disease is marked by a febrile response, malaise, coagulopathy and vascular permeability culminating in death. Case fatality rates can reach 90% depending on the etiologic agent. Currently, there is no approved antiviral treatment. Because of the high case fatality, risk of importation and the potential to use these agents as biological weapons, development of countermeasures to these agents is a high priority. The sporadic nature of disease outbreaks and the ethical issues associated with conducting a human trial for such diseases make human studies impractical; therefore, development of countermeasures must occur in relevant animal models. Non-human primates are superior models to study infectious disease because their immune system is similar to humans and they are good predictors of efficacy in vaccine development and other intervention strategies. This review article summarizes viral hemorrhagic fever non-human primate models.

  5. Human quadrupeds, primate quadrupedalism, and Uner Tan Syndrome.

    Directory of Open Access Journals (Sweden)

    Liza J Shapiro

    Full Text Available Since 2005, an extensive literature documents individuals from several families afflicted with "Uner Tan Syndrome (UTS," a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or "devolution." In support of this idea, individuals with "UTS" are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary "reversal," no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with "UTS", we found that these humans almost exclusively used lateral sequence-not diagonal sequence-quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the "devolution" hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-09-01

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

  7. Non-Human Primate Models of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-11-18

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

  11. Primate vocal communication: a useful tool for understanding human speech and language evolution?

    Science.gov (United States)

    Fedurek, Pawel; Slocombe, Katie E

    2011-04-01

    Language is a uniquely human trait, and questions of how and why it evolved have been intriguing scientists for years. Nonhuman primates (primates) are our closest living relatives, and their behavior can be used to estimate the capacities of our extinct ancestors. As humans and many primate species rely on vocalizations as their primary mode of communication, the vocal behavior of primates has been an obvious target for studies investigating the evolutionary roots of human speech and language. By studying the similarities and differences between human and primate vocalizations, comparative research has the potential to clarify the evolutionary processes that shaped human speech and language. This review examines some of the seminal and recent studies that contribute to our knowledge regarding the link between primate calls and human language and speech. We focus on three main aspects of primate vocal behavior: functional reference, call combinations, and vocal learning. Studies in these areas indicate that despite important differences, primate vocal communication exhibits some key features characterizing human language. They also indicate, however, that some critical aspects of speech, such as vocal plasticity, are not shared with our primate cousins. We conclude that comparative research on primate vocal behavior is a very promising tool for deepening our understanding of the evolution of human speech and language, but much is still to be done as many aspects of monkey and ape vocalizations remain largely unexplored.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Olivier eJoly

    2014-09-01

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

  14. Irrational choice behavior in human and nonhuman primates.

    Science.gov (United States)

    Perdue, Bonnie M; Brown, Ella R

    2018-03-01

    Choice behavior in humans has motivated a large body of research with a focus on whether decisions can be considered to be rational. In general, humans prefer having choice, as do a number of other species that have been tested, even though having increased choice does not necessarily yield a positive outcome. Humans have been found to choose an option more often only because the opportunity to select it was diminishing, an example of a deviation from economic rationality. Here we extend this paradigm to nonhuman primates in an effort to understand the mechanisms underlying this finding. In this study, we presented two groups of laboratory monkeys, capuchins (Cebus apella) and rhesus macaques (Macaca mulatta), as well as human subjects, with a computerized task in which subjects were presented with two differently colored icons. When the subject selected an icon, differing numbers of food pellets were dispensed (or points were assigned), making each icon correspond to a certain level of risk (one icon yielded 1 or 4 pellets/points and the other yielded 2 or 3). Initially, both options remained constantly available and we established choice preference scores for each subject. Then, we assessed preference patterns once the options were not continuously available. Specifically, choosing one icon would cause the other to shrink in size on the screen and eventually disappear if never selected. Selecting it would restore it to its full size. As predicted, humans shifted their risk preferences in the diminishing options phase, choosing to click on both icons more equally in order to keep both options available. At the group level, capuchin monkeys showed this pattern as well, but there was a great deal of individual variability in both capuchins and macaques. The present work suggests that there is some degree of continuity between human and nonhuman primates in the desire to have choice simply for the sake of having choice.

  15. Genetic engineering in nonhuman primates for human disease modeling.

    Science.gov (United States)

    Sato, Kenya; Sasaki, Erika

    2018-02-01

    Nonhuman primate (NHP) experimental models have contributed greatly to human health research by assessing the safety and efficacy of newly developed drugs, due to their physiological and anatomical similarities to humans. To generate NHP disease models, drug-inducible methods, and surgical treatment methods have been employed. Recent developments in genetic and developmental engineering in NHPs offer new options for producing genetically modified disease models. Moreover, in recent years, genome-editing technology has emerged to further promote this trend and the generation of disease model NHPs has entered a new era. In this review, we summarize the generation of conventional disease model NHPs and discuss new solutions to the problem of mosaicism in genome-editing technology.

  16. The Evolution of Trypanosomes Infecting Humans and Primates

    Directory of Open Access Journals (Sweden)

    Stevens Jamie

    1998-01-01

    Full Text Available Based on phylogenetic analysis of 18S rRNA sequences and clade taxon composition, this paper adopts a biogeographical approach to understanding the evolutionary relationships of the human and primate infective trypanosomes, Trypanosoma cruzi, T. brucei, T. rangeli and T. cyclops. Results indicate that these parasites have divergent origins and fundamentally different patterns of evolution. T. cruzi is placed in a clade with T. rangeli and trypanosomes specific to bats and a kangaroo. The predominantly South American and Australian origins of parasites within this clade suggest an ancient southern super-continent origin for ancestral T. cruzi, possibly in marsupials. T. brucei clusters exclusively with mammalian, salivarian trypanosomes of African origin, suggesting an evolutionary history confined to Africa, while T. cyclops, from an Asian primate appears to have evolved separately and is placed in a clade with T. (Megatrypanum species. Relating clade taxon composition to palaeogeographic evidence, the divergence of T. brucei and T. cruzi can be dated to the mid-Cretaceous, around 100 million years before present, following the separation of Africa, South America and Euramerica. Such an estimate of divergence time is considerably more recent than those of most previous studies based on molecular clock methods. Perhaps significantly, Salivarian trypanosomes appear, from these data, to be evolving several times faster than Schizotrypanum species, a factor which may have contributed to previous anomalous estimates of divergence times.

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

    Science.gov (United States)

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

    2015-09-01

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

  18. African Non-Human Primates Host Diverse Enteroviruses.

    Directory of Open Access Journals (Sweden)

    Illich Manfred Mombo

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

  19. Variable responses of human and non-human primate gut microbiomes to a Western diet.

    Science.gov (United States)

    Amato, Katherine R; Yeoman, Carl J; Cerda, Gabriela; Schmitt, Christopher A; Cramer, Jennifer Danzy; Miller, Margret E Berg; Gomez, Andres; Turner, Trudy R; Wilson, Brenda A; Stumpf, Rebecca M; Nelson, Karen E; White, Bryan A; Knight, Rob; Leigh, Steven R

    2015-11-16

    The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.

  20. The ten-thousand year fever: rethinking human and wild primate malarias

    National Research Council Canada - National Science Library

    Cormier, Loretta A

    2011-01-01

    "Malaria is one of the oldest recorded diseases in human history, and its 10,000-year relationship to primates can teach us why it will be one of the most serious threats to humanity in the 21st century...

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

    Science.gov (United States)

    Aversi-Ferreira, Roqueline A. G. M. F.; Bretas, Rafael Vieira; Maior, Rafael Souto; Davaasuren, Munkhzul; Paraguassú-Chaves, Carlos Alberto; Nishijo, Hisao; Aversi-Ferreira, Tales Alexandre

    2014-01-01

    The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing. PMID:24860810

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Breno Frederico de Carvalho Dominguez Souza

    2014-09-01

    Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the ‘90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.

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

    Directory of Open Access Journals (Sweden)

    B.G. Nath

    2013-08-01

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

  5. Looking forward to a PET scanner designed for non-human primates

    International Nuclear Information System (INIS)

    Tanaka, Keiji

    1992-01-01

    The cerebral cortex of non-human primates has been divided, mainly by anatomical techniques, into an enormous number of areas. We are looking forward to a PET scanner designed for non-human primates, with a hope to determine active brain regions when the animal does various cognitive tasks. This measurement with PET can be combined with single cell recordings and anatomical tracer studies in non-human primates. Another big hope is to detect a change of active regions as the learning advances. (author)

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Damiana F Ravasi

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

  9. Hunger enhances consistent economic choices in non-human primates.

    Science.gov (United States)

    Yamada, Hiroshi

    2017-05-24

    Hunger and thirst are fundamental biological processes that drive consumption behavior in humans and non-human animals. While the existing literature in neuroscience suggests that these satiety states change how consumable rewards are represented in the brain, it remains unclear as to how they change animal choice behavior and the underlying economic preferences. Here, I used combined techniques from experimental economics, psychology, and neuroscience to measure food preferences of marmoset monkeys (Callithrix jacchus), a recently developed primate model for neuroscience. Hunger states of animals were manipulated by scheduling feeding intervals, resulting in three different conditions: sated, non-sated, and hungry. During these hunger states, animals performed pairwise choices of food items, which included all possible pairwise combinations of five different food items except for same-food pairs. Results showed that hunger enhanced economic rationality, evident as a decrease of transitivity violations (item A was preferred to item B, and B to C, but C was preferred to A). Further analysis demonstrated that hungry monkeys chose more-preferred items over less-preferred items in a more deterministic manner, while the individual food preferences appeared to remain stable across hunger states. These results suggest that hunger enhances consistent choice behavior and shifts animals towards efficient outcome maximization.

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

    Directory of Open Access Journals (Sweden)

    Laura Clara Grandi

    2016-09-01

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

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

    Science.gov (United States)

    Amato, Katherine R

    2016-01-01

    The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    W. Tecumseh Fitch

    2013-07-01

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

  13. Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

    Science.gov (United States)

    Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

    2017-01-01

    The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

  14. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    Energy Technology Data Exchange (ETDEWEB)

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  15. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    International Nuclear Information System (INIS)

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro

    2014-01-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

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

    Directory of Open Access Journals (Sweden)

    C.L. Vitral

    1998-08-01

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

  17. From cheetahs to chimpanzees: a comparative review of the drivers of human-carnivore conflict and human-primate conflict.

    Science.gov (United States)

    Dickman, Amy J

    2012-01-01

    Human-wildlife conflict is a growing conservation threat, and is increasingly of importance to primate conservationists. Despite this, relatively little work has been done to date on the drivers of human-primate conflict, especially compared to other conflict-causing taxa such as large carnivores. However, the drivers of conflict are often very similar across species, so conflict researchers can learn important lessons from work conducted on other taxa. This paper discusses 8 key factors which are likely to affect how hostile people are towards wildlife and any damage they cause--6 of these are common to both carnivores and primates, while one is much more applicable to carnivores and the other is specific to primates. These conflict drivers involve numerous social and cultural factors, and highlight the importance of truly understanding the local drivers of conflict in order to develop effective mitigation strategies. Copyright © 2013 S. Karger AG, Basel.

  18. Measles: What we have learned from non-human primate models

    NARCIS (Netherlands)

    R.L. de Swart (Rik)

    2018-01-01

    textabstractStudies in non-human primates (NHPs) have been crucial for our understanding of measles as a high impact viral disease of humans. Over a century ago, inoculations of NHPs with filtered secretions from measles patients first identified a virus as the causative agent of this disease. In

  19. Conserving social-ecological systems in Indonesia: human-nonhuman primate interconnections in Bali and Sulawesi.

    Science.gov (United States)

    Riley, Erin P; Fuentes, Agustín

    2011-01-01

    An important question asked by primatologists and conservationists alike is: what is the relevance of primates and primate conservation for ecosystem conservation? The goal of this article is to contribute to this dialogue by advocating the use of a research perspective that focuses on the dynamics of human-nonhuman primate sympatry and interaction (i.e., ethnoprimatology) in order to better understand complex social-ecological systems and to inform their conservation management. This perspective/approach is based largely on the recognition that human primates are important components of all ecological systems and that niche construction is a fundamental feature of their adaptive success. To demonstrate the relevance of the human-nonhuman primate interface for ecosystem conservation, we provide examples from our research from two islands in the Indonesian archipelago: Bali and Sulawesi. In Bali, humans and long-tail macaques coexist in a system that creates favorable environments for the macaques. This anthropogenic landscape and the economic and ecological relationships between humans and monkeys on Bali provide insight into sustainable systems of human/nonhuman primate coexistence. In Lore Lindu National Park in Central Sulawesi, villagers and Tonkean macaques overlap in their use of both forest and cultivated resources. The finding that the Arenga pinnata palm is extremely important for both villagers and macaques points to a conservation management recommendation that may help protect the overall ecosystem; the cultivation and propagation of mutually important tree species at forest-agricultural ecotone as a means to curb crop raiding and to alleviate farmer's perceived need to clear additional forest.

  20. Primate social attention: Species differences and effects of individual experience in humans, great apes, and macaques.

    Directory of Open Access Journals (Sweden)

    Fumihiro Kano

    Full Text Available When viewing social scenes, humans and nonhuman primates focus on particular features, such as the models' eyes, mouth, and action targets. Previous studies reported that such viewing patterns vary significantly across individuals in humans, and also across closely-related primate species. However, the nature of these individual and species differences remains unclear, particularly among nonhuman primates. In large samples of human and nonhuman primates, we examined species differences and the effects of experience on patterns of gaze toward social movies. Experiment 1 examined the species differences across rhesus macaques, nonhuman apes (bonobos, chimpanzees, and orangutans, and humans while they viewed movies of various animals' species-typical behaviors. We found that each species had distinct viewing patterns of the models' faces, eyes, mouths, and action targets. Experiment 2 tested the effect of individuals' experience on chimpanzee and human viewing patterns. We presented movies depicting natural behaviors of chimpanzees to three groups of chimpanzees (individuals from a zoo, a sanctuary, and a research institute differing in their early social and physical experiences. We also presented the same movies to human adults and children differing in their expertise with chimpanzees (experts vs. novices or movie-viewing generally (adults vs. preschoolers. Individuals varied within each species in their patterns of gaze toward models' faces, eyes, mouths, and action targets depending on their unique individual experiences. We thus found that the viewing patterns for social stimuli are both individual- and species-specific in these closely-related primates. Such individual/species-specificities are likely related to both individual experience and species-typical temperament, suggesting that primate individuals acquire their unique attentional biases through both ontogeny and evolution. Such unique attentional biases may help them learn

  1. Primate social attention: Species differences and effects of individual experience in humans, great apes, and macaques.

    Science.gov (United States)

    Kano, Fumihiro; Shepherd, Stephen V; Hirata, Satoshi; Call, Josep

    2018-01-01

    When viewing social scenes, humans and nonhuman primates focus on particular features, such as the models' eyes, mouth, and action targets. Previous studies reported that such viewing patterns vary significantly across individuals in humans, and also across closely-related primate species. However, the nature of these individual and species differences remains unclear, particularly among nonhuman primates. In large samples of human and nonhuman primates, we examined species differences and the effects of experience on patterns of gaze toward social movies. Experiment 1 examined the species differences across rhesus macaques, nonhuman apes (bonobos, chimpanzees, and orangutans), and humans while they viewed movies of various animals' species-typical behaviors. We found that each species had distinct viewing patterns of the models' faces, eyes, mouths, and action targets. Experiment 2 tested the effect of individuals' experience on chimpanzee and human viewing patterns. We presented movies depicting natural behaviors of chimpanzees to three groups of chimpanzees (individuals from a zoo, a sanctuary, and a research institute) differing in their early social and physical experiences. We also presented the same movies to human adults and children differing in their expertise with chimpanzees (experts vs. novices) or movie-viewing generally (adults vs. preschoolers). Individuals varied within each species in their patterns of gaze toward models' faces, eyes, mouths, and action targets depending on their unique individual experiences. We thus found that the viewing patterns for social stimuli are both individual- and species-specific in these closely-related primates. Such individual/species-specificities are likely related to both individual experience and species-typical temperament, suggesting that primate individuals acquire their unique attentional biases through both ontogeny and evolution. Such unique attentional biases may help them learn efficiently about their

  2. 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

    2016-01-01

    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 ([3H]dT, or TdR) at early embryonic ages were killed at different intervals postinjection to follow postmitotic cells' positional changes. As expected in primates, most SP neurons generated in the ventricular zone initially migrate radially, together with prospective layer 6 neurons. Surprisingly, mostly during midgestation, SP cells become secondarily displaced and widespread into the expanding SP zone, which becomes particularly wide subjacent to the association cortical areas and underneath the summit of its folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and corticocortical axons is mainly responsible for this region-dependent passive dispersion of the SP cells. Histologic and immunohistochemical comparison with the human SP at corresponding fetal ages indicates that the same developmental events occur in both primate species. PMID:27503885

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

    Directory of Open Access Journals (Sweden)

    Michael T Bethune

    2008-02-01

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

  4. Leptospiral agglutinins in captive and free ranging non-human primates in Sarawak, Malaysia

    Directory of Open Access Journals (Sweden)

    S. Thayaparan

    2014-06-01

    Full Text Available Aim: The proposed study was carried out to determine the extent of exposure to leptospirosis in non-human primates. Materials and Methods: Trapping of non-human primates was carried out opportunistically around the Bako National Park and the Matang Wildlife Center in the vicinity of human settlements and tourism areas of Sarawak. Blood samples were obtained from the saphenous vein to determine the presence of antibodies by the Microscopic Agglutination Test (MAT to 17 serovars of Leptospira commonly found in Malaysia. Results: This study reports the screening of twelve primates (eight captive and four free ranging for leptospirosis. Eight of the 12 monkeys (66.6%; 95% CI 34.9-90.1 reacted against one or two serovars of Leptospira (Lai and Leptospira Lepto175. The serovar Lai is considered pathogenic for different mammals, including humans. Leptospira Lepto 175 has been identified as an intermediate strain and further studies are being undertaken on this serovar. Conclusion: These results are important as primates may act as reservoirs of Leptospira spp. for humans, which may potentially affect tourism (economic loss, conservation efforts and public health.

  5. A microneedle patch containing measles vaccine is immunogenic in non-human primates.

    Science.gov (United States)

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

    2015-09-08

    Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify the logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID₅₀) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Functional correlates of the position of the axis of rotation of the mandible during chewing in non-human primates.

    Science.gov (United States)

    Iriarte-Diaz, Jose; Terhune, Claire E; Taylor, Andrea B; Ross, Callum F

    2017-10-01

    The location of the axis of rotation (AoR) of the mandible was quantified using the helical axis (HA) in eight individuals from three species of non-human primates: Papio anubis, Cebus apella, and Macaca mulatta. These data were used to test three hypotheses regarding the functional significance of anteroposterior condylar translation - an AoR located inferior to the temporomandibular joint (TMJ) - during chewing: minimizing impingement of the gonial region on cervical soft tissue structures during jaw opening; avoiding stretching of the inferior alveolar neurovascular bundle (IANB); and increasing jaw-elevator muscle torques. The results reveal that the HA is located near the occlusal plane in Papio and Cebus, but closer to the condyle in Macaca; is located anteroinferior to the TMJ during both opening and closing in Papio, as well as during opening in Macaca and Cebus; and varies in its location during closing in Macaca and Cebus. The impingement hypothesis is not supported by interspecific variation in HA location: species with larger gonial angles like Cebus do not have more inferiorly located HAs than species with more obtuse mandibular angles like Papio. However, intraspecific variation provides some support for the impingement hypothesis. The HA seldom passes near or through the lingula, falsifying the hypothesis that its location is determined by the sphenomandibular ligament, and the magnitudes of strain associated with a HA at the TMJ would not be large enough to cause problematic stretching of the IANB. HA location does affect muscle moment arms about the TMJ, with implications for the torque generation capability of the jaw-elevator muscles. In Cebus, a HA farther away from the TMJ is associated with larger jaw-elevator muscle moment arms about the joint than if it were at the TMJ. The effects of HA location on muscle strain and muscle moment arms are largest at large gapes and smallest at low gapes, suggesting that if HA location is of functional

  7. Biocompatibility Assessment of Detonation Nanodiamond in Non-Human Primates and Rats Using Histological, Hematologic, and Urine Analysis.

    Science.gov (United States)

    Moore, Laura; Yang, Junyu; Lan, Thanh T Ha; Osawa, Eiji; Lee, Dong-Keun; Johnson, William D; Xi, Jianzhong; Chow, Edward Kai-Hua; Ho, Dean

    2016-08-23

    Detonation nanodiamonds (DNDs) have been widely explored for biomedical applications ranging from cancer therapy to magnetic resonance imaging due to several promising properties. These include faceted surfaces that mediate potent drug binding and water coordination that have resulted in marked enhancements to the efficacy and safety of drug delivery and imaging. In addition, scalable processing of DNDs yields uniform particles. Furthermore, a broad spectrum of biocompatibility studies has shown that DNDs appear to be well-tolerated. Prior to the clinical translation of DNDs for indications that are addressed via intravenous administration, comprehensive assessment of DND safety in both small and large animal preclinical models is needed. This article reports the results of a DND biocompatibility study in both non-human primates and rats. The rat study was performed as a multiple dose subacute investigation in two cohorts that lasted for 2 weeks and included histological, serum, and urine analysis. The non-human primate study was performed as a dual gender, multiple dose, and long-term investigation in both standard/clinically relevant and elevated dosing cohorts that lasted for 6 months and included comprehensive serum, urine, histological, and body weight analysis. The results from these studies indicate that NDs are well-tolerated at clinically relevant doses. Examination of dose-dependent changes in biomarker levels provides important guidance for the downstream in-human validation of DNDs for clinical drug delivery and imaging.

  8. Diet-microbe co-metabolic interactions in wild primates reveal clues on human evolution

    Czech Academy of Sciences Publication Activity Database

    Gomez, A. M.; Rothman, J. M.; Petrželková, Klára Judita; Yeoman, C. J.; Vlčková, K.; Umana, J. D.; Carr, M.; Modrý, D.; Tod, A.; Nelson, K.; Stumpf, R. M.; Wilson, B. A.; White, B. A.; Leigh, S. R.

    2015-01-01

    Roč. 156, č. 60 (2015), s. 149 ISSN 0002-9483. [Annual Meeting of the American Association of Physical Anthropologists /84./. 25.03.2015-28.03.2015, St Louis] Institutional support: RVO:68081766 Keywords : wild primates * human evolution Subject RIV: EE - Microbiology, Virology

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

    Johnston, Kevin; Everling, Stefan

    2008-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    de la Torre, Ignacio; Hirata, Satoshi

    2015-11-19

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

  13. 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 Soil-transmitted helminths (STHs are a major health concern in tropical and sub-tropical countries. Oesophagostomum infection is considered endemic to West Africa but has also been identified in Uganda, East Africa, among primates (including humans. However, the taxonomy and ecology of Oesophagostomum in Uganda have not been studied, except for in chimpanzees (Pan troglodytes, which are infected by both O. bifurcum and O. stephanostomum.We studied Oesophagostomum in Uganda in a community of non-human primates that live in close proximity to humans. Prevalence estimates based on microscopy were lower than those based on polymerase chain reaction (PCR, indicating greater sensitivity of PCR. Prevalence varied among host species, with humans and red colobus (Procolobus rufomitratus infected at lowest prevalence (25% and 41% by PCR, respectively, and chimpanzees, olive baboons (Papio anubis, and l'hoest monkeys (Cercopithecus lhoesti infected at highest prevalence (100% by PCR in all three species. Phylogenetic regression showed that primates travelling further and in smaller groups are at greatest risk of infection. Molecular phylogenetic analyses revealed three cryptic clades of Oesophagostomum that were not distinguishable based on morphological characteristics of their eggs. Of these, the clade with the greatest host range had not previously been described genetically. This novel clade infects humans, as well as five other species of primates.Multiple cryptic forms of Oesophagostomum circulate in the people and primates of western Uganda, and parasite clades differ in host range and cross-species transmission potential. Our results expand knowledge about human Oesophagostomum infection beyond the West African countries of Togo and Ghana, where the parasite is a known public health concern. Oesophagostomum infection in humans may be common throughout Sub-Saharan Africa, and the transmission of this neglected STH among primates, including zoonotic

  14. Variable postpartum responsiveness among humans and other primates with "cooperative breeding": A comparative and evolutionary perspective.

    Science.gov (United States)

    Hrdy, Sarah B

    2016-01-01

    This article is part of a Special Issue "Parental Care".Until recently, evolutionists reconstructing mother-infant bonding among human ancestors relied on nonhuman primate models characterized by exclusively maternal care, overlooking the highly variable responsiveness exhibited by mothers in species with obligate reliance on allomaternal care and provisioning. It is now increasingly recognized that apes as large-brained, slow maturing, and nutritionally dependent for so long as early humans were, could not have evolved unless "alloparents" (group members other than genetic parents), in addition to parents, had helped mothers to care for and provision offspring, a rearing system known as "cooperative breeding." Here I review situation-dependent maternal responses ranging from highly possessive to permissive, temporarily distancing, rejecting, or infanticidal, documented for a small subset of cooperatively breeding primates. As in many mammals, primate maternal responsiveness is influenced by physical condition, endocrinological priming, prior experience and local environments (especially related to security). But mothers among primates who evolved as cooperative breeders also appear unusually sensitive to cues of social support. In addition to more "sapient" or rational decision-making, humankind's deep history of cooperative breeding must be considered when trying to understand the extremely variable responsiveness of human mothers. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. First comparative study of primate morphological and molecular evolutionary rates including muscle data: implications for the tempo and mode of primate and human evolution

    Science.gov (United States)

    Diogo, Rui; Peng, Zuogang; Wood, Bernard

    2013-01-01

    Here we provide the first report about the rates of muscle evolution derived from Bayesian and parsimony cladistic analyses of primate higher-level phylogeny, and compare these rates with published rates of molecular evolution. It is commonly accepted that there is a ‘general molecular slow-down of hominoids’, but interestingly the rates of muscle evolution in the nodes leading and within the hominoid clade are higher than those in the vast majority of other primate clades. The rate of muscle evolution at the node leading to Homo (1.77) is higher than that at the nodes leading to Pan (0.89) and particularly to Gorilla (0.28). Notably, the rates of muscle evolution at the major euarchontan and primate nodes are different, but within each major primate clade (Strepsirrhini, Platyrrhini, Cercopithecidae and Hominoidea) the rates at the various nodes, and particularly at the nodes leading to the higher groups (i.e. including more than one genera), are strikingly similar. We explore the implications of these new data for the tempo and mode of primate and human evolution. PMID:23320764

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

    Science.gov (United States)

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-08-01

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

  17. Sex differences in quadrupedal walking gaits of Uner Tan syndrome cases, healthy humans and nonhuman primates.

    Science.gov (United States)

    Tan, Uner

    2017-03-01

    Uner Tan syndrome (UTS) cases with habitual quadrupedal locomotion (QL), impaired intelligence, and dysarthric or no speech predominantly use lateral sequence (LS) gait like nonprimates rather than the predominantly diagonal sequence (DS) gait of nonhuman primates. However, these studies neglected possible sex-related differences in these gait types. (1) To assess the possible sex-related gait types in UTS cases, healthy infants and adults with requested QL, and the nonhuman primates. (2) To test the hypothesis that sex differences may exist in quadrupedal walking gaits in UTS cases, healthy humans, and nonhuman primates. The UTS cases were filmed, the other study groups were taken from public open 'youtube' videos, which were used to assess the walking gait types as DS and LS. The right and left hind-limb phase values were calculated separately for males and females to allow a possible sex difference in walking gaits to be determined. Females predominantly used DS gait, contrary to males with predominantly LS gait. Consistent with the working hypothesis, the results suggested a biological sex-related trend in preferred walking gaits exists in all of the human and nonhuman primates using QL.

  18. 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......-eclampsia also occurs in these species, such information may reveal the evolutionary roots of this disease of impaired maternal-fetal interaction....

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Comparative primate obstetrics: Observations of 15 diurnal births in wild gelada monkeys (Theropithecus gelada) and their implications for understanding human and nonhuman primate birth evolution.

    Science.gov (United States)

    Nguyen, Nga; Lee, Laura M; Fashing, Peter J; Nurmi, Niina O; Stewart, Kathrine M; Turner, Taylor J; Barry, Tyler S; Callingham, Kadie R; Goodale, C Barret; Kellogg, Bryce S; Burke, Ryan J; Bechtold, Emily K; Claase, Megan J; Eriksen, G Anita; Jones, Sorrel C Z; Kerby, Jeffrey T; Kraus, Jacob B; Miller, Carrie M; Trew, Thomas H; Zhao, Yi; Beierschmitt, Evan C; Ramsay, Malcolm S; Reynolds, Jason D; Venkataraman, Vivek V

    2017-05-01

    The birth process has been studied extensively in many human societies, yet little is known about this essential life history event in other primates. Here, we provide the most detailed account of behaviors surrounding birth for any wild nonhuman primate to date. Over a recent ∼10-year period, we directly observed 15 diurnal births (13 live births and 2 stillbirths) among geladas (Theropithecus gelada) at Guassa, Ethiopia. During each birth, we recorded the occurrence (or absence) of 16 periparturitional events, chosen for their potential to provide comparative evolutionary insights into the factors that shaped birth behaviors in humans and other primates. We found that several events (e.g., adopting standing crouched positions, delivering infants headfirst) occurred during all births, while other events (e.g., aiding the infant from the birth canal, licking infants following delivery, placentophagy) occurred during, or immediately after, most births. Moreover, multiparas (n = 9) were more likely than primiparas (n = 6) to (a) give birth later in the day, (b) isolate themselves from nearby conspecifics while giving birth, (c) aid the infant from the birth canal, and (d) consume the placenta. Our results suggest that prior maternal experience may contribute to greater competence or efficiency during the birth process. Moreover, face presentations (in which infants are born with their neck extended and their face appearing first, facing the mother) appear to be the norm for geladas. Lastly, malpresentations (in which infants are born in the occiput anterior position more typical of human infants) may be associated with increased mortality in this species. We compare the birth process in geladas to those in other primates (including humans) and discuss several key implications of our study for advancing understanding of obstetrics and the mechanism of labor in humans and nonhuman primates. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Riley Eleanor

    2011-02-01

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

  3. Reminiscences of a journeyman scientist: studies of thermoregulation in non-human primates and humans.

    Science.gov (United States)

    Adair, Eleanor Reed

    2008-12-01

    After graduating from Mount Holyoke College in 1948 where I majored in experimental psychology I worked at the College for 2 years with the Johns Hopkins Thermophysiological Unit. My graduate work later at the University of Wisconsin, centering on sensory psychology, culminated in my 1955 PhD thesis on human dark adaptation. I continued work in sensory psychology later with Neal Miller at Yale and then moved to the John B. Pierce Foundation--a Yale affiliate--where I began the studies of thermoregulation that constitute the center of my scientific career. Those studies were largely--later wholly--conducted using microwave energy as a thermal load and were thus published in Bioelectromagnetics even as I played an active role in the Bioelectromagnetics Society. In the beginning this work was centered on the responses of Squirrel Monkeys to thermal loads. Later, serving as Senior Scientist at the Air Force Research Laboratory at San Antonio, I completed an extensive analysis of thermal regulation in humans. I consider this work of special note inasmuch as the extraordinary human thermoregulatory ability was surely among the attributes that were paramount in initially separating humans from the other anthropoid primates.

  4. 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.

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

    Science.gov (United States)

    Bradley, Matthew J; Vicente, Diego A; Bograd, Benjamin A; Sanders, Erin M; Leonhardt, Crystal L; Elster, Eric A; Davis, Thomas A

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Matthew J. Bradley

    2017-11-01

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

  7. Human object-similarity judgments reflect and transcend the primate-IT object representation

    Directory of Open Access Journals (Sweden)

    Marieke eMur

    2013-03-01

    Full Text Available Primate inferior temporal (IT cortex is thought to contain a high-level representation of objects at the interface between vision and semantics. This suggests that the perceived similarity of real-world objects might be predicted from the IT representation. Here we show that objects that elicit similar activity patterns in human IT tend to be judged as similar by humans. The IT representation explained the human judgments better than early visual cortex, other ventral stream regions, and a range of computational models. Human similarity judgments exhibited category clusters that reflected several categorical divisions that are prevalent in the IT representation of both human and monkey, including the animate/inanimate and the face/body division. Human judgments also reflected the within-category representation of IT. However, the judgments transcended the IT representation in that they introduced additional categorical divisions. In particular, human judgments emphasized human-related additional divisions between human and nonhuman animals and between man-made and natural objects. Human IT was more similar to monkey IT than to human judgments. One interpretation is that IT has evolved visual feature detectors that distinguish between animates and inanimates and between faces and bodies because these divisions are fundamental to survival and reproduction for all primate species, and that other brain systems serve to more flexibly introduce species-dependent and evolutionarily more recent divisions.

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

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Li

    2016-10-01

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

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

    OpenAIRE

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

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally per...

  10. Primate social attention : species differences and effects of individual experience in humans, great apes, and macaques

    OpenAIRE

    Kano, Fumihiro; Shepherd, Stephen V.; Hirata, Satoshi; Call, Josep

    2018-01-01

    Financial support came from Japan Society for Promotion of Science (JSPS) [grant numbers: KAKENHI 26885040, 16K21108 to FK, KAKENHI 26245069, 16H06301, 16H06283, JSPS-LGP-U04 to SH] and Ministry of Education, Culture, Sports, Science and Technology (MEXT) [K-CONNEX to FK], and the European Research Council [SOMICS 609819 to JC]. When viewing social scenes, humans and nonhuman primates focus on particular features, such as the models’ eyes, mouth, and action targets. Previous studies report...

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

    Science.gov (United States)

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

    2012-01-01

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

  12. The ethical justification for the use of non-human primates in research: the Weatherall report revisited.

    Science.gov (United States)

    Arnason, Gardar

    2017-10-14

    The Weatherall report on the use of non-human primates in research was published in 2006. Its main conclusion was that there is a strong scientific case for the use of non-human primates in some cases, but the report stressed the importance of evaluating each case in the light of the availability of alternatives. In addition to arguing for the scientific necessity of using non-human primates in research, the report also provided an ethical justification. As could be expected, the report was harshly criticised by animal rights groups, but in the academic literature, only two critical replies appeared. In what follows, I will describe the ethical justification for non-human primate research as it is laid out in the Weatherall report and then consider the criticism in the academic literature. I conclude that the report's ethical justification for the use of non-human primates in research, in particular in basic neuroscientific research, has not been convincingly challenged by its critics. Since the criticism of the report is limited and represents only a small part of the academic discussion about the use of non-human primates in research, and a still smaller part of the ethical discussion about animal research, it is important that the discussion continue both at the academic and social level. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. The 'other faunivory' revisited: Insectivory in human and non-human primates and the evolution of human diet.

    Science.gov (United States)

    McGrew, William C

    2014-06-01

    The role of invertebrates in the evolution of human diet has been under-studied by comparison with vertebrates and plants. This persists despite substantial knowledge of the importance of the 'other faunivory', especially insect-eating, in the daily lives of non-human primates and traditional human societies, especially hunters and gatherers. Most primates concentrate on two phyla, Mollusca and Arthropoda, but of the latter's classes, insects (especially five orders: Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Orthoptera) are paramount. An insect product, bees' honey, is particularly important, and its collection shows a reversal of the usual sexual division of labor. Human entomophagy involves advanced technology (fire, containers) and sometimes domestication. Insectivory provides comparable calorific and nutritional benefits to carnivory, but with different costs. Much insectivory in hominoids entails elementary technology used in extractive foraging, such as termite fishing by chimpanzees. Elucidating insectivory in the fossil and paleontological record is challenging, but at least nine avenues are available: remains, lithics, residues, DNA, coprolites, dental microwear, stable isotopes, osteology, and depictions. All are in play, but some have been more successful so far than others. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-01-01

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. PMID:24503087

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.

    Science.gov (United States)

    Absinta, Martina; Ha, Seung-Kwon; Nair, Govind; Sati, Pascal; Luciano, Nicholas J; Palisoc, Maryknoll; Louveau, Antoine; Zaghloul, Kareem A; Pittaluga, Stefania; Kipnis, Jonathan; Reich, Daniel S

    2017-10-03

    Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.

  19. Comparative Review of Antimicrobial Resistance in Humans and Nonhuman Primates.

    Science.gov (United States)

    Kim, Jeffrey; Coble, Dondrae J; Salyards, Gregory W; Habing, Gregory G

    2018-04-02

    Antimicrobial resistance (AMR) presents serious threats to human and animal health. Although AMR of pathogens is often evaluated independently between humans and animals, comparative analysis of AMR between humans and animals is necessary for zoonotic pathogens. Major surveillance systems monitor AMR of zoonotic pathogens in humans and food animals, but comprehensive AMR data in veterinary medicine is not diligently monitored for most animal species with which humans commonly contact, including NHP. The objective of this review is to provide a complete report of the prevalences of AMR among zoonotic bacteria that present the greatest threats to NHP, occupational, and public health. High prevalences of AMR exist among Shigella, Campylobacter, and Yersinia, including resistance to antimicrobials important to public health, such as macrolides. Despite improvements in regulations, standards, policies, practices, and zoonotic awareness, occupational exposures to and illnesses due to zoonotic pathogens continue to be reported and, given the documented prevalences of AMR, constitute an occupational and public health risk. However, published literature is sparse, thus indicating the need for veterinarians to proactively monitor AMR in dangerous zoonotic bacteria, to enable veterinarians to make more informed decisions to maximize antimicrobial therapy and minimize occupational risk.

  20. A theory of social thermoregulation in human primates.

    Science.gov (United States)

    IJzerman, Hans; Coan, James A; Wagemans, Fieke M A; Missler, Marjolein A; van Beest, Ilja; Lindenberg, Siegwart; Tops, Mattie

    2015-01-01

    Beyond breathing, the regulation of body temperature-thermoregulation-is one of the most pressing concerns for many animals. A dysregulated body temperature has dire consequences for survival and development. Despite the high frequency of social thermoregulation occurring across many species, little is known about the role of social thermoregulation in human (social) psychological functioning. We outline a theory of social thermoregulation and reconsider earlier research on people's expectations of their social world (i.e., attachment) and their prediction of the social world. We provide support and outline a research agenda that includes consequences for individual variation in self-regulatory strategies and capabilities. In our paper, we discuss physiological, neural, and social processes surrounding thermoregulation. Emphasizing social thermoregulation in particular, we appeal to the economy of action principle and the hierarchical organization of human thermoregulatory systems. We close with future directions of a crucial aspect of human functioning: the social regulation of body temperature.

  1. Gene therapy in nonhuman primate models of human autoimmune disease

    NARCIS (Netherlands)

    t'Hart, B. A.; Vervoordeldonk, M.; Heeney, J. L.; Tak, P. P.

    2003-01-01

    Before autoimmune diseases in humans can be treated with gene therapy, the safety and efficacy of the used vectors must be tested in valid experimental models. Monkeys, such as the rhesus macaque or the common marmoset, provide such models. This publication reviews the state of the art in monkey

  2. The mirror system in human and nonhuman primates.

    Science.gov (United States)

    Orban, Guy A

    2014-04-01

    The description of the mirror neuron system provided by Cook et al. is incomplete for the macaque, and incorrect for humans. This is relevant to exaptation versus associative learning as the underlying mechanism generating mirror neurons, and to the sensorimotor learning as evidence for the authors' viewpoint. The proposed additional testing of the mirror system in rodents is unrealistic.

  3. Primate-specific spliced PMCHL RNAs are non-protein coding in human and macaque tissues

    Directory of Open Access Journals (Sweden)

    Delerue-Audegond Audrey

    2008-12-01

    Full Text Available Abstract Background Brain-expressed genes that were created in primate lineage represent obvious candidates to investigate molecular mechanisms that contributed to neural reorganization and emergence of new behavioural functions in Homo sapiens. PMCHL1 arose from retroposition of a pro-melanin-concentrating hormone (PMCH antisense mRNA on the ancestral human chromosome 5p14 when platyrrhines and catarrhines diverged. Mutations before divergence of hylobatidae led to creation of new exons and finally PMCHL1 duplicated in an ancestor of hominids to generate PMCHL2 at the human chromosome 5q13. A complex pattern of spliced and unspliced PMCHL RNAs were found in human brain and testis. Results Several novel spliced PMCHL transcripts have been characterized in human testis and fetal brain, identifying an additional exon and novel splice sites. Sequencing of PMCHL genes in several non-human primates allowed to carry out phylogenetic analyses revealing that the initial retroposition event took place within an intron of the brain cadherin (CDH12 gene, soon after platyrrhine/catarrhine divergence, i.e. 30–35 Mya, and was concomitant with the insertion of an AluSg element. Sequence analysis of the spliced PMCHL transcripts identified only short ORFs of less than 300 bp, with low (VMCH-p8 and protein variants or no evolutionary conservation. Western blot analyses of human and macaque tissues expressing PMCHL RNA failed to reveal any protein corresponding to VMCH-p8 and protein variants encoded by spliced transcripts. Conclusion Our present results improve our knowledge of the gene structure and the evolutionary history of the primate-specific chimeric PMCHL genes. These genes produce multiple spliced transcripts, bearing short, non-conserved and apparently non-translated ORFs that may function as mRNA-like non-coding RNAs.

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

    Directory of Open Access Journals (Sweden)

    Olivia B. Tomeo

    2017-07-01

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

  5. Goddess Science, Primates and Feminism. Primatology and Human Nature Seeking

    Directory of Open Access Journals (Sweden)

    Aleksandra Derra

    2015-12-01

    Full Text Available The Author introduces basic aims, notions, methodological tools and theories of primatology. Underlining crucial role this discipline has played in defining human nature, she points out how it has changed due to its social duties, close relations to popular culture and growing impact of female researchers with feminist sensitivity. She posits the question about female or feminist character of primatology, indicating that the answer depends on taking for granted certain disputable assumptions about femininity and female scientific methods. Subsequently she presents androcentric bias of primatology studies (concerning sexuality, reproduction, male domination, female roles, aggression, and its later critique. Finally she problematizes culture/nature division which is used both in scientific and everyday discourse.

  6. Two organizing principles of vocal production: Implications for nonhuman and human primates.

    Science.gov (United States)

    Owren, Michael J; Amoss, R Toby; Rendall, Drew

    2011-06-01

    Vocal communication in nonhuman primates receives considerable research attention, with many investigators arguing for similarities between this calling and speech in humans. Data from development and neural organization show a central role of affect in monkey and ape sounds, however, suggesting that their calls are homologous to spontaneous human emotional vocalizations while having little relation to spoken language. Based on this evidence, we propose two principles that can be useful in evaluating the many and disparate empirical findings that bear on the nature of vocal production in nonhuman and human primates. One principle distinguishes production-first from reception-first vocal development, referring to the markedly different role of auditory-motor experience in each case. The second highlights a phenomenon dubbed dual neural pathways, specifically that when a species with an existing vocal system evolves a new functionally distinct vocalization capability, it occurs through emergence of a second parallel neural pathway rather than through expansion of the extant circuitry. With these principles as a backdrop, we review evidence of acoustic modification of calling associated with background noise, conditioning effects, audience composition, and vocal convergence and divergence in nonhuman primates. Although each kind of evidence has been interpreted to show flexible cognitively mediated control over vocal production, we suggest that most are more consistent with affectively grounded mechanisms. The lone exception is production of simple, novel sounds in great apes, which is argued to reveal at least some degree of volitional vocal control. If also present in early hominins, the cortically based circuitry surmised to be associated with these rudimentary capabilities likely also provided the substrate for later emergence of the neural pathway allowing volitional production in modern humans. © 2010 Wiley-Liss, Inc.

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

    Science.gov (United States)

    Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun-Ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

    2011-01-01

    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.

  8. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Meyer, Jerrold S.; Hamel, Amanda F.

    2014-01-01

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

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

    Science.gov (United States)

    Meyer, Jerrold S; Hamel, Amanda F

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction. © The Author 2014. Published by Oxford University Press on

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

    Science.gov (United States)

    Whiten, Andrew; van de Waal, Erica

    2017-11-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - 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

  14. 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.

  15. Olive baboons: a non-human primate model for testing dengue virus type 2 replication.

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Castro, Jorge; Odoyo, Damián; Hitler, Rikoi; Munene, Elephas; Romero, Yaremis; Ochola, Lucy; Cosme, Karelia; Kariuki, Thomas; Guillén, Gerardo; Hermida, Lisset

    2013-12-01

    This study evaluated the use of a non-human primate, the olive baboon (Papio anubis), as a model of dengue infection. Olive baboons closely resemble humans genetically and physiologically and have been used extensively for assessing novel vaccine formulations. Two doses of dengue virus type 2 (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Similarly, African green monkeys received the same quantity of virus and acted as positive controls. Following exposure, high levels of viremia were detected in both animal species. There was a trend to detect more days of viremia and more homogeneous viral titers in animals receiving the low viral dose. In addition, baboons infected with the virus generally exhibited positive virus isolation 1 day later than African green monkeys. Humoral responses consisting of antiviral and neutralizing antibodies were detected in all animals after infection. We conclude that baboons provide an alternative non-human primate species for experimental DENV-2 infection and we recommend their use for further tests of vaccines, administering the lowest dose assayed: 10(3) pfu. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Biosocial Conservation: Integrating Biological and Ethnographic Methods to Study Human-Primate Interactions.

    Science.gov (United States)

    Setchell, Joanna M; Fairet, Emilie; Shutt, Kathryn; Waters, Siân; Bell, Sandra

    2017-01-01

    Biodiversity conservation is one of the grand challenges facing society. Many people interested in biodiversity conservation have a background in wildlife biology. However, the diverse social, cultural, political, and historical factors that influence the lives of people and wildlife can be investigated fully only by incorporating social science methods, ideally within an interdisciplinary framework. Cultural hierarchies of knowledge and the hegemony of the natural sciences create a barrier to interdisciplinary understandings. Here, we review three different projects that confront this difficulty, integrating biological and ethnographic methods to study conservation problems. The first project involved wildlife foraging on crops around a newly established national park in Gabon. Biological methods revealed the extent of crop loss, the species responsible, and an effect of field isolation, while ethnography revealed institutional and social vulnerability to foraging wildlife. The second project concerned great ape tourism in the Central African Republic. Biological methods revealed that gorilla tourism poses risks to gorillas, while ethnography revealed why people seek close proximity to gorillas. The third project focused on humans and other primates living alongside one another in Morocco. Incorporating shepherds in the coproduction of ecological knowledge about primates built trust and altered attitudes to the primates. These three case studies demonstrate how the integration of biological and social methods can help us to understand the sustainability of human-wildlife interactions, and thus promote coexistence. In each case, an integrated biosocial approach incorporating ethnographic data produced results that would not otherwise have come to light. Research that transcends conventional academic boundaries requires the openness and flexibility to move beyond one's comfort zone to understand and acknowledge the legitimacy of "other" kinds of knowledge. It is

  17. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

    Science.gov (United States)

    Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M

    2013-05-24

    Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

  19. Preclinical evaluation of VIS513, a therapeutic antibody against dengue virus, in non-human primates.

    Science.gov (United States)

    Ong, Eugenia Z; Budigi, Yadunanda; Tan, Hwee Cheng; Robinson, Luke N; Rowley, Kirk J; Winnett, Alexander; Hobbie, Sven; Shriver, Zachary; Babcock, Gregory J; Ooi, Eng Eong

    2017-08-01

    Despite useful in vivo activity, no therapeutic against dengue virus (DENV) has demonstrated efficacy in clinical trials. Herein, we explored dosing and virological endpoints to guide the design of human trials of VIS513, a pan-serotype anti-DENV IgG1 antibody, in non-human primates (NHPs). Dosing VIS513 pre- or post-peak viremia in NHPs neutralized infectious DENV although RNAemia remained detectable post-treatment; differential interaction of human IgGs with macaque Fc-gamma receptors may delay clearance of neutralized DENV. Our findings suggest useful antiviral utility of VIS513 and highlight an important consideration when evaluating virological endpoints of trials for anti-DENV biologics. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Simone M Cinini

    2014-03-01

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

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

    Science.gov (United States)

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

    2015-05-01

    Aggression is a key component for social behaviour and can have an adaptive value or deleterious consequences. Here, we review the role of sex-related differences in aggressive behaviour in both human and nonhuman primates. First, we address aggression in primates, which varies deeply between species, both in intensity and in display, ranging from animals that are very aggressive, such as chimpanzees, to the nonaggressive bonobos. Aggression also influences the hierarchical structure of gorillas and chimpanzees, and is used as the main tool for dealing with other groups. With regard to human aggression, it can be considered a relevant adaptation for survival or can have negative impacts on social interaction for both sexes. Gender plays a critical role in aggressive and competitive behaviours, which are determined by a cascade of physiological changes, including GABAergic and serotonergic systems, and sex neurosteroids. The understanding of the neurobiological bases and behavioural determinants of different types of aggression is fundamental for minimising these negative impacts. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Misako Komatsu

    2017-09-01

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

  4. Large Volume, Behaviorally-relevant Illumination for Optogenetics in Non-human Primates.

    Science.gov (United States)

    Acker, Leah C; Pino, Erica N; Boyden, Edward S; Desimone, Robert

    2017-10-03

    This protocol describes a large-volume illuminator, which was developed for optogenetic manipulations in the non-human primate brain. The illuminator is a modified plastic optical fiber with etched tip, such that the light emitting surface area is > 100x that of a conventional fiber. In addition to describing the construction of the large-volume illuminator, this protocol details the quality-control calibration used to ensure even light distribution. Further, this protocol describes techniques for inserting and removing the large volume illuminator. Both superficial and deep structures may be illuminated. This large volume illuminator does not need to be physically coupled to an electrode, and because the illuminator is made of plastic, not glass, it will simply bend in circumstances when traditional optical fibers would shatter. Because this illuminator delivers light over behaviorally-relevant tissue volumes (≈ 10 mm 3 ) with no greater penetration damage than a conventional optical fiber, it facilitates behavioral studies using optogenetics in non-human primates.

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

    Czech Academy of Sciences Publication Activity Database

    Doležalová, J.; Vallo, Peter; Petrželková, Klára Judita; Foitová, I.; Nurcahyo, W.; Mudakikwa, A.; Hashimoto, C.; Jirků, M.; Lukeš, J.; Scholz, T.; Modrý, D.

    2015-01-01

    Roč. 142, č. 10 (2015), s. 1278-1289 ISSN 0031-1820 R&D Projects: GA ČR GA524/06/0264; GA ČR GA206/09/0927 Institutional support: RVO:68081766 Keywords : Bertiella * Anoplocephala * phylogeny * primates * zoonotic potential Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 3.031, year: 2015

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  7. Sexual size dimorphism, canine dimorphism, and male-male competition in primates: where do humans fit in?

    Science.gov (United States)

    Plavcan, J Michael

    2012-03-01

    Sexual size dimorphism is generally associated with sexual selection via agonistic male competition in nonhuman primates. These primate models play an important role in understanding the origins and evolution of human behavior. Human size dimorphism is often hypothesized to be associated with high rates of male violence and polygyny. This raises the question of whether human dimorphism and patterns of male violence are inherited from a common ancestor with chimpanzees or are uniquely derived. Here I review patterns of, and causal models for, dimorphism in humans and other primates. While dimorphism in primates is associated with agonistic male mate competition, a variety of factors can affect male and female size, and thereby dimorphism. The causes of human sexual size dimorphism are uncertain, and could involve several non-mutually-exclusive mechanisms, such as mate competition, resource competition, intergroup violence, and female choice. A phylogenetic reconstruction of the evolution of dimorphism, including fossil hominins, indicates that the modern human condition is derived. This suggests that at least some behavioral similarities with Pan associated with dimorphism may have arisen independently, and not directly from a common ancestor.

  8. Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini)

    Science.gov (United States)

    2009-01-01

    In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus,Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates. PMID:21637455

  9. Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini).

    Science.gov (United States)

    Gifalli-Iughetti, Cristiani; Koiffmann, Célia P

    2009-10-01

    In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus,Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates.

  10. Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini

    Directory of Open Access Journals (Sweden)

    Cristiani Gifalli-Iughetti

    2009-01-01

    Full Text Available In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus, Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62. The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates.

  11. Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts.

    Science.gov (United States)

    van der Lee, Robin; Wiel, Laurens; van Dam, Teunis J P; Huynen, Martijn A

    2017-10-13

    Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cell membrane proteins (e.g. pattern recognition, complement, cytokines, immune receptors, MHC, Siglecs). We also find evidence for positive selection in reproduction and chromosome segregation (e.g. centromere-associated CENPO, CENPT), apolipoproteins, smell/taste receptors and mitochondrial proteins. Focusing on the virus-host interaction, we retrieve most evolutionary conflicts known to influence antiviral activity (e.g. TRIM5, MAVS, SAMHD1, tetherin) and predict 70 novel cases through integration with virus-human interaction data. Protein structure analysis further identifies positive selection in the interaction interfaces between viruses and their cellular receptors (CD4-HIV; CD46-measles, adenoviruses; CD55-picornaviruses). Finally, primate PSG consistently show high sequence variation in human exomes, suggesting ongoing evolution. Our curated dataset of positive selection is a rich source for studying the genetics underlying human (antiviral) phenotypes. Procedures and data are available at https://github.com/robinvanderlee/positive-selection. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Chronic Antibody-Mediated Rejection in Nonhuman Primate Renal Allografts: Validation of Human Histological and Molecular Phenotypes.

    Science.gov (United States)

    Adam, B A; Smith, R N; Rosales, I A; Matsunami, M; Afzali, B; Oura, T; Cosimi, A B; Kawai, T; Colvin, R B; Mengel, M

    2017-11-01

    Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0.92). This three-gene set correlated with classic features of AMR, including glomerulitis, capillaritis, glomerulopathy, C4d deposition, and DSAs (r = 0.39-0.63, p < 0.001). Principal component analysis confirmed the association between three-gene set expression and AMR and highlighted the ambiguity of v lesions and ptc lesions between AMR and T cell-mediated rejection (TCMR). Elevated three-gene set expression corresponded with the development of immunopathological evidence of rejection and often preceded it. Many recipients demonstrated mixed AMR and TCMR, suggesting that this represents the natural pattern of rejection. These data provide NHP animal model validation of recent updates to the Banff classification including the assessment of molecular markers for diagnosing AMR. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    Czech Academy of Sciences Publication Activity Database

    Doležalová, J.; Vallo, P.; Petrželková, Klára Judita; Foitová, I.; Nurcahyo, W.; Mudakikwa, A.; Hashimoto, C.; Jirků, Milan; Lukeš, Julius; Scholz, Tomáš; Modrý, David

    2015-01-01

    Roč. 142, č. 10 (2015), s. 1278-1289 ISSN 0031-1820 R&D Projects: GA MŠk(CZ) EE2.3.30.0032; GA ČR GA206/09/0927 Institutional support: RVO:60077344 Keywords : Bertiella * Anoplocephala * phylogeny * primates * zoonotic potential Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 3.031, year: 2015

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

    OpenAIRE

    Marco A B Almeida; Jader da C Cardoso; Edmilson Dos Santos; Daltro F da Fonseca; Laura L Cruz; Fernando J C Faraco; Marilina A Bercini; Kátia C Vettorello; Mariana A Porto; Renate Mohrdieck; Tani M S Ranieri; Maria T Schermann; Alethéa F Sperb; Francisco Z Paz; Zenaida M A Nunes

    2014-01-01

    Author Summary Yellow fever (YF) is a viral hemorrhagic disease that affects humans as well as several species of non-human primates, especially New World monkeys found in South America. Yellow fever virus (YFV) is maintained in a natural cycle involving tree-hole breeding mosquitoes and non-human primates hosts. Because YF is often fatal in susceptible New World monkey populations, sudden die-offs of New World monkeys or epizootics can signal YFV circulation in an environment where humans ma...

  15. Regulation of EGF and Prostaglandin Expression during Neonatal Gastrointestinal Injury in a Non-Human Primate Explant Model

    Science.gov (United States)

    2017-05-05

    Neonatal Gastrointestinal Injury in a Non-Human Primate Explant Model presented at/published to Pediatric Academic Societies Meeting, San Francisco CA...Medical Center, San Antonio, Texas’ 2Department of Biology, Trinity University, San Antonio, Texas’ JDepartment of Pediatrics /Division of Neonatology

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

    CSIR Research Space (South Africa)

    Ripamonti, U

    2008-01-01

    Full Text Available Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) biomimetic matrices. HA/β-TCP biomimetic matrices in a pre...

  17. 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.

  18. Epidemiology and molecular characterization of Cryptosporidium spp. in humans, wild primates, and domesticated animals in the Greater Gombe Ecosystem, Tanzania.

    Science.gov (United States)

    Parsons, Michele B; Travis, Dominic; Lonsdorf, Elizabeth V; Lipende, Iddi; Roellig, Dawn M; Roellig, Dawn M Anthony; Collins, Anthony; Kamenya, Shadrack; Zhang, Hongwei; Xiao, Lihua; Gillespie, Thomas R

    2015-02-01

    Cryptosporidium is an important zoonotic parasite globally. Few studies have examined the ecology and epidemiology of this pathogen in rural tropical systems characterized by high rates of overlap among humans, domesticated animals, and wildlife. We investigated risk factors for Cryptosporidium infection and assessed cross-species transmission potential among people, non-human primates, and domestic animals in the Gombe Ecosystem, Kigoma District, Tanzania. A cross-sectional survey was designed to determine the occurrence and risk factors for Cryptosporidium infection in humans, domestic animals and wildlife living in and around Gombe National Park. Diagnostic PCR revealed Cryptosporidium infection rates of 4.3% in humans, 16.0% in non-human primates, and 9.6% in livestock. Local streams sampled were negative. DNA sequencing uncovered a complex epidemiology for Cryptosporidium in this system, with humans, baboons and a subset of chimpanzees infected with C. hominis subtype IfA12G2; another subset of chimpanzees infected with C. suis; and all positive goats and sheep infected with C. xiaoi. For humans, residence location was associated with increased risk of infection in Mwamgongo village compared to one camp (Kasekela), and there was an increased odds for infection when living in a household with another positive person. Fecal consistency and other gastrointestinal signs did not predict Cryptosporidium infection. Despite a high degree of habitat overlap between village people and livestock, our results suggest that there are distinct Cryptosporidium transmission dynamics for humans and livestock in this system. The dominance of C. hominis subtype IfA12G2 among humans and non-human primates suggest cross-species transmission. Interestingly, a subset of chimpanzees was infected with C. suis. We hypothesize that there is cross-species transmission from bush pigs (Potaochoerus larvatus) to chimpanzees in Gombe forest, since domesticated pigs are regionally absent. Our

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Immune response to the West Nile virus in aged non-human primates.

    Directory of Open Access Journals (Sweden)

    Anne M Wertheimer

    2010-12-01

    Full Text Available Risk of encephalitis from West Nile virus (WNV infection increases dramatically with age. Understanding the basis of this susceptibility requires development of suitable animal models. Here, we investigated the immune response to WNV in old non-human primates.We investigated clinical, immunological and virological correlates of WNV infection in aging non-human primates. Aged (17-30 yrs and adult (6-9 yrs Rhesus macaques (RM were challenged with WNV in the presence or the absence of the mosquito salivary gland extract (SGE to approximate natural infection. None of the 26 animals exhibited clinical signs of the disease. Quantitative PCR suggested discrete and short-lived viremia, but infectious virus was never isolated. There was markedly increased, age-independent, proliferation of CD3(- non-B cells, followed by B-cell proliferation, which correlated to the loss of detectable WNV genomes. Moreover, animals primed with mosquito salivary gland extract exhibited reduced circulating WNV RNA. While we found the expected age-associated reduction in T cell proliferation, adaptive immunity did not correlate with infection outcome. That was further confirmed in a cohort of thymectomized and/or CD8 T-cell depleted Cynomolgus macaques (CM; N = 15, who also failed to develop WNV disease.Results are consistent with strong and age-independent innate resistance of macaques against WNV challenge. This animal model is therefore not suitable for vaccine and therapeutic testing against WNV. However, understanding the basis of their innate resistance against WNV in macaques could provide helpful clues to improve anti-WNV protection of older adults.

  1. Rate of evolution in brain-expressed genes in humans and other primates.

    Directory of Open Access Journals (Sweden)

    Hurng-Yi Wang

    2007-02-01

    Full Text Available Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM and then conducted three-way comparisons among (i mouse, OWM, and human, and (ii OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse, a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i faster evolution in gene expression, and (ii a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.

  2. Humans and great apes share increased neocortical neuropeptide Y innervation compared to other haplorhine primates

    Directory of Open Access Journals (Sweden)

    Mary Ann eRaghanti

    2014-02-01

    Full Text Available Neuropeptide Y (NPY plays a role in a variety of basic physiological functions and has also been implicated in regulating cognition, including learning and memory. A decrease in neocortical NPY has been reported for Alzheimer’s disease, schizophrenia, bipolar disorder, and depression, potentially contributing to associated cognitive deficits. The goal of the present analysis was to examine variation in neocortical NPY-immunoreactive axon and varicosity density among haplorhine primates (monkeys, apes, and humans. Stereologic methods were used to measure the ratios of NPY-expressing axon length density to total neuron density (ALv/Nv and NPY-immunoreactive varicosity density to neuron density (Vv/Nv, as well as the mean varicosity spacing in neocortical areas 10, 24, 44, and 22 (Tpt of humans, African great apes, New World monkeys, and Old World monkeys. Humans and great apes showed increased cortical NPY innervation relative to monkey species for ALv/Nv and Vv/Nv. Furthermore, humans and great apes displayed a conserved pattern of varicosity spacing across cortical areas and layers, with no differences between cortical layers or among cortical areas. These phylogenetic differences may be related to shared life history variables and may reflect specific cognitive abilities.

  3. Alu Sb2 subfamily is present in all higher primates but was most succesfully amplified in humans

    Energy Technology Data Exchange (ETDEWEB)

    Richer, C.; Zietkiewicz, E.; Labuda, D. [Universite de Montreal, Que (Canada)

    1994-09-01

    Alu repeats can be classified into subfamilies which amplified in primate genomes at different evolutionary time periods. A young Alu subfamily, Sb2, with a characteristic 7-nucleotide duplication at position 256, has been described in seven human loci. An Sb2 insertion found near the HD gene was unique to two HD families, indicating that Sb2 was still retropositionally active. Here, we have shown that the Sb2 insertion in the CHOL locus was similarly rare, being absent in 120 individuals of Caucasian, Oriental and Black origin. In contrast, Sb2 inserts in five other loci were found fixed (non-polymorphic), based on measurements in the same population sample, but absent from orthologous positions in higher apes. This suggest that Sb2 repeats spread relatively early in the human lineage following divergence from other primates and that these elements may be human-specific. By quantitative PCR, we investigated the presence of Sb2 sequences in different primate DNA, using one PCR primer anchored at the 5{prime} Alu-end and the other complementary to the duplicated Sb2-specific segment. With an Sb2-containing plasmid as a standard, we estimated the number of Sb2 repeats at 1500-1800 copies per human haploid equivalent; corresponding numbers in chimpanzee and gorilla were almost two orders of magnitude lower, while the signal observed in orangutan and gibbon DNAs was consistent with the presence of a single copy. The analysis of 22 human, 11 chimpanzee and 10 gorilla sequences indicates that the Alu Sb2 dispersed independently in these three primate lineages; gorilla consensus differs from the human Sb2 sequence by one position, while all chimpanzee repeats have their linker expanded by up to eight A-residues. Should they be thus considered as separate subfamilies? It is possible that sequence modifications with respect to the human consensus are responsible for poor retroposition of Sb2 in apes.

  4. Segmental duplications and evolutionary acquisition of UV damage response in the SPATA31 gene family of primates and humans.

    Science.gov (United States)

    Bekpen, Cemalettin; Künzel, Sven; Xie, Chen; Eaaswarkhanth, Muthukrishnan; Lin, Yen-Lung; Gokcumen, Omer; Akdis, Cezmi A; Tautz, Diethard

    2017-03-06

    Segmental duplications are an abundant source for novel gene functions and evolutionary adaptations. This mechanism of generating novelty was very active during the evolution of primates particularly in the human lineage. Here, we characterize the evolution and function of the SPATA31 gene family (former designation FAM75A), which was previously shown to be among the gene families with the strongest signal of positive selection in hominoids. The mouse homologue for this gene family is a single copy gene expressed during spermatogenesis. We show that in primates, the SPATA31 gene duplicated into SPATA31A and SPATA31C types and broadened the expression into many tissues. Each type became further segmentally duplicated in the line towards humans with the largest number of full-length copies found for SPATA31A in humans. Copy number estimates of SPATA31A based on digital PCR show an average of 7.5 with a range of 5-11 copies per diploid genome among human individuals. The primate SPATA31 genes also acquired new protein domains that suggest an involvement in UV response and DNA repair. We generated antibodies and show that the protein is re-localized from the nucleolus to the whole nucleus upon UV-irradiation suggesting a UV damage response. We used CRISPR/Cas mediated mutagenesis to knockout copies of the gene in human primary fibroblast cells. We find that cell lines with reduced functional copies as well as naturally occurring low copy number HFF cells show enhanced sensitivity towards UV-irradiation. The acquisition of new SPATA31 protein functions and its broadening of expression may be related to the evolution of the diurnal life style in primates that required a higher UV tolerance. The increased segmental duplications in hominoids as well as its fast evolution suggest the acquisition of further specific functions particularly in humans.

  5. The importance of surface-based cues for face discrimination in non-human primates.

    Science.gov (United States)

    Parr, Lisa A; Taubert, Jessica

    2011-07-07

    Understanding how individual identity is processed from faces remains a complex problem. Contrast reversal, showing faces in photographic negative, impairs face recognition in humans and demonstrates the importance of surface-based information (shading and pigmentation) in face recognition. We tested the importance of contrast information for face encoding in chimpanzees and rhesus monkeys using a computerized face-matching task. Results showed that contrast reversal (positive to negative) selectively impaired face processing in these two species, although the impairment was greater for chimpanzees. Unlike chimpanzees, however, monkeys performed just as well matching negative to positive faces, suggesting that they retained some ability to extract identity information from negative faces. A control task showed that chimpanzees, but not rhesus monkeys, performed significantly better matching face parts compared with whole faces after a contrast reversal, suggesting that contrast reversal acts selectively on face processing, rather than general visual-processing mechanisms. These results confirm the importance of surface-based cues for face processing in chimpanzees and humans, while the results were less salient for rhesus monkeys. These findings make a significant contribution to understanding the evolution of cognitive specializations for face processing among primates, and suggest potential differences between monkeys and apes.

  6. Cortical networks for encoding near and far space in the non-human primate.

    Science.gov (United States)

    Cléry, Justine; Guipponi, Olivier; Odouard, Soline; Wardak, Claire; Ben Hamed, Suliann

    2018-04-19

    While extra-personal space is often erroneously considered as a unique entity, early neuropsychological studies report a dissociation between near and far space processing both in humans and in monkeys. Here, we use functional MRI in a naturalistic 3D environment to describe the non-human primate near and far space cortical networks. We describe the co-occurrence of two extended functional networks respectively dedicated to near and far space processing. Specifically, far space processing involves occipital, temporal, parietal, posterior cingulate as well as orbitofrontal regions not activated by near space, possibly subserving the processing of the shape and identity of objects. In contrast, near space processing involves temporal, parietal, prefrontal and premotor regions not activated by far space, possibly subserving the preparation of an arm/hand mediated action in this proximal space. Interestingly, this network also involves somatosensory regions, suggesting a cross-modal anticipation of touch by a nearby object. Last, we also describe cortical regions that process both far and near space with a preference for one or the other. This suggests a continuous encoding of relative distance to the body, in the form of a far-to-near gradient. We propose that these cortical gradients in space representation subserve the physically delineable peripersonal spaces described in numerous psychology and psychophysics studies. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sara Garamszegi

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

  8. Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.

    Directory of Open Access Journals (Sweden)

    Kai Weng

    Full Text Available Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1 as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.

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

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    Shanaz A Ghandhi

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

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

    Science.gov (United States)

    Ghandhi, Shanaz A; Turner, Helen C; Shuryak, Igor; Dugan, Gregory O; Bourland, J Daniel; Olson, John D; Tooze, Janet A; Morton, Shad R; Batinic-Haberle, Ines; Cline, J Mark; Amundson, Sally A

    2018-01-01

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

  11. 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

    -life as longer oligonucleotides. Pharmacology studies in both mice and non-human primates were conducted with a 13-mer LNA oligonucleotide against apoB, and the data showed that repeated dosing of the 13-mer at 1-2 mg/kg/week was sufficient to provide a significant and long lasting lowering of non...... using the LNA chemistry. Conclusively, we present a 13-mer LNA oligonucleotide with therapeutic potential that produce beneficial cholesterol lowering effect in non-human primates....

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

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    Hiroko Shimada

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

  13. Studies of Nicotinic Receptors in Non-human Primates Using PET and SPECT

    International Nuclear Information System (INIS)

    Kassiou, M.; University of Sydney,

    2002-01-01

    Full text: Observations of abnormalities in the densities of nicotinic acetylcholine receptors (nAChRs) in the brains of smokers and patients with various CNS disorders has suggested that noninvasive imaging and quantification of nAChRs using PET and SPECT would be useful. This offers further the understanding of the involvement of these receptors in these conditions as well as insight into their role in the normal functioning of the brain. As a prelude to human studies, newly developed PET and SPECT radioligands are first evaluated in animals to determine their suitability for clinical imaging. In the neurosciences the most widespread application of PET and SPECT in animal imaging has been in the study of non-human primates. The larger animals allow the performance of quantitative imaging to be achieved on conventional clinical human scanners. The use of non-human primates for imaging nAChRs in models of Parkinson's disease and smoking is described below. Nicotinic acetylcholine receptors have been implicated in PD's since it has been demonstrated postmortem that cortical nAChRs are reduced and parallel the increase in dementia that occurs in PD patients. In experimental animals it has shown that nicotine protects against MPTP-induced degeneration. MPTP degeneration representing the most widely used and validated animal model of PD. Also, a number of studies have indicated that smokers have a lower than expected incidence of PD, suggesting a protective effect of nicotine. In order to study nAChRs using PET we have developed [ 76 Br]bromoepibatidine. This work was carried out at the Service Hospitalier Frederic Joliot, Orsay France as part of the France-Australia collaboration. In papio papio baboon the brain uptake of [ 76 Br]bromoepibatidine was high with preferential localisation in the thalamus. The [ 76 Br]bromoepibatidine uptake is consistent with the known cerebral nAChR distribution in primates. The radioactivity in thalamus, striatum and cortices was

  14. Non human primate models for Alzheimer's disease-related research and drug discovery

    NARCIS (Netherlands)

    Van Dam, Debby; De Deyn, Peter Paul

    2017-01-01

    Introduction: Pathophysiological mechanisms underlying Alzheimer's disease (AD) remain insufficiently documented for the identification of accurate diagnostic markers and purposeful target discovery and development. Nonhuman primates (NHPs) have important translational value given their close

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

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    Kofler Julia

    2012-05-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  17. Working Memory: A Cognitive Limit to Non-Human Primate Recursive Thinking Prior to Hominid Evolution

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    Dwight W. Read

    2008-10-01

    Full Text Available In this paper I explore the possibility that recursion is not part of the cognitive repertoire of non-human primates such as chimpanzees due to limited working memory capacity. Multiple lines of data, from nut cracking to the velocity and duration of cognitive development, imply that chimpanzees have a short-term memory size that limits working memory to dealing with two, or at most three, concepts at a time. If so, as a species they lack the cognitive capacity for recursive thinking to be integrated into systems of social organization and communication. If this limited working memory capacity is projected back to a common ancestor for Pan and Homo, it follows that early hominid ancestors would have had limited working memory capacity. Hence we should find evidence for expansion of working memory capacity during hominid evolution reflected in changes in the products of conceptually framed activities such as stone tool production. Data on the artifacts made by our hominid ancestors support this expansion hypothesis for hominid working memory, thereby leading to qualitative differences between Pan and Homo.

  18. Non-human primate FOG develops with advanced parkinsonism induced by MPTP Treatment.

    Science.gov (United States)

    Revuelta, Gonzalo J; Uthayathas, Subramaniam; Wahlquist, Amy E; Factor, Stewart A; Papa, Stella M

    2012-10-01

    Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) and other forms of parkinsonism. The anatomical or pathophysiological correlates are poorly understood largely due to the lack of a well-established animal model. Here we studied whether FOG is reproduced in the non-human primate (NHP) model of PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (Genus Macaca, n=29) were examined for the development of FOG, and the leg movements were recorded with accelerometry. The relationships between developing FOG and the animals' characteristics, the MPTP treatments, and the modeled outcomes were determined. In parkinsonian monkeys FOG developed frequently (48%) manifesting similar characteristics to those seen in PD patients. In addition, FOG episodes in the monkey were accompanied by leg trembling with the typical duration (2-10s) and frequency (~7 Hz). The development of NHP FOG was significantly associated with the severity of parkinsonism, as shown by high motor disability scores (≥ 20) and levodopa-induced dyskinesia scores (p=0.01 and p=0.04, respectively). Differences in demographics and MPTP treatments (doses, treatment duration, etc.) had no influence on NHP FOG occurrence, with the exception of gender that showed FOG predominance in males (p=0.03). The unique features of FOG in PD can be replicated in severely parkinsonian macaques, and this represents the first description of a FOG animal model. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    Tal Noy-Porat

    2016-03-01

    Full Text Available Ricin, derived from the castor bean plant Ricinus communis, is one of the most potent and lethal toxins known, against which there is no available antidote. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this study was to isolate high affinity anti-ricin antibodies that possess potent toxin-neutralization capabilities. Two non-human primates were immunized with either a ricin-holotoxin- or subunit-based vaccine, to ensure the elicitation of diverse high affinity antibodies. By using a comprehensive set of primers, immune scFv phage-displayed libraries were constructed and panned. A panel of 10 antibodies (five directed against the A subunit of ricin and five against the B subunit was isolated and reformatted into a full-length chimeric IgG. All of these antibodies were found to neutralize ricin in vitro, and several conferred full protection to ricin-intoxicated mice when given six hours after exposure. Six antibodies were found to possess exceptionally high affinity toward the toxin, with KD values below pM (koff < 1 × 10−7 s−1 that were well correlated with their ability to neutralize ricin. These antibodies, alone or in combination, could be used for the development of a highly-effective therapeutic preparation for post-exposure treatment of ricin intoxication.

  20. Multichannel micromanipulator and chamber system for recording multineuronal activity in alert, non-human primates.

    Science.gov (United States)

    Gray, Charles M; Goodell, Baldwin; Lear, Alex

    2007-07-01

    We describe the design and performance of an electromechanical system for conducting multineuron recording experiments in alert non-human primates. The system is based on a simple design, consisting of a microdrive, control electronics, software, and a unique type of recording chamber. The microdrive consists of an aluminum frame, a set of eight linear actuators driven by computer-controlled miniature stepping motors, and two printed circuit boards (PCBs) that provide connectivity to the electrodes and the control electronics. The control circuitry is structured around an Atmel RISC-based microcontroller, which sends commands to as many as eight motor control cards, each capable of controlling eight motors. The microcontroller is programmed in C and uses serial communication to interface with a host computer. The graphical user interface for sending commands is written in C and runs on a conventional personal computer. The recording chamber is low in profile, mounts within a circular craniotomy, and incorporates a removable internal sleeve. A replaceable Sylastic membrane can be stretched across the bottom opening of the sleeve to provide a watertight seal between the cranial cavity and the external environment. This greatly reduces the susceptibility to infection, nearly eliminates the need for routine cleaning, and permits repeated introduction of electrodes into the brain at the same sites while maintaining the watertight seal. The system is reliable, easy to use, and has several advantages over other commercially available systems with similar capabilities.

  1. Manganese Neurotoxicity: New Perspectives from Behavioral, Neuroimaging, and Neuropathological Studies in Humans and Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Tomas R Guilarte

    2013-06-01

    Full Text Available Manganese (Mn is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinsonism. Historically, studies on the effects of Mn in humans and experimental animals have been concerned with effects on the basal ganglia and the dopaminergic system as it relates to movement abnormalities. However, emerging studies are beginning to provide significant evidence of Mn effects on cortical structures and cognitive function at lower levels than previously recognized. This review advances new knowledge of putative mechanisms by which exposure to excess levels of Mn alters neurobiological systems and produces neurological deficits not only in the basal ganglia but also in the cerebral cortex. The emerging evidence suggests that working memory is significantly affected by chronic Mn exposure and this may be mediated by alterations in brain structures associated with the working memory network including the caudate nucleus in the striatum, frontal cortex and parietal cortex. Dysregulation of the dopaminergic system may play an important role in both the movement abnormalities as well as the neuropsychiatric and cognitive function deficits that have been described in humans and non-human primates exposed to Mn.

  2. An autonomous, automated and mobile device to concurrently assess several cognitive functions in group-living non-human primates.

    Science.gov (United States)

    Fizet, Jonas; Rimele, Adam; Pebayle, Thierry; Cassel, Jean-Christophe; Kelche, Christian; Meunier, Hélène

    2017-11-01

    Research methods in cognitive neuroscience using non-human primates have undergone notable changes over the last decades. Recently, several research groups have described freely accessible devices equipped with a touchscreen interface. Two characteristics of such systems are of particular interest: some apparatuses include automated identification of subjects, while others are mobile. Here, we designed, tested and validated an experimental system that, for the first time, combine automatization and mobility. Moreover, our system allows autonomous learning and testing of cognitive performance in group-living subjects, including follow-up assessments. The mobile apparatus is designed to be available 24h a day, 7days a week, in a typical confined primate breeding and housing facility. Here we present as proof of concept, the results of two pilot studies. We report that rhesus macaques (Macaca mulatta) learned the tasks rapidly and achieved high-level of stable performance. Approaches of this kind should be developed for future pharmacological and biomedical studies in non-human primates. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Geographic and species association of hepatitis B virus genotypes in non-human primates

    International Nuclear Information System (INIS)

    Starkman, S.E.; MacDonald, D.M.; Lewis, J.C.M.; Holmes, E.C.; Simmonds, P.

    2003-01-01

    Infection with hepatitis B virus (HBV) has been detected in human populations throughout the world, as well as in a number of ape species (Pan troglodytes, Gorilla gorilla, gibbons [Nomascus and Hylobates species] and Pongo pygmaeus). To investigate the distribution of naturally occurring HBV infection in these species and other African Old World monkey species (Cercopithecidae), we screened 137 plasma samples from mainly wild caught animals by polymerase chain reaction (PCR) using several of highly conserved primers from the HB surface (HBs) gene, and for HBs antigen (HBsAg) by ELISA. None of the 93 Cercopithecidae screened (6 species) showed PCR or serology evidence for HBV infection; in contrast 2 from 8 chimpanzees and 5 from 22 gibbons were PCR-positive with each set of primers. Complete genome sequences from each of the positive apes were obtained and compared with all previously published complete and surface gene sequences. This extended phylogenetic analysis indicated that HBV variants from orangutans were interspersed by with HBV variants from southerly distributed gibbon species (H. agilis and H. moloch) occupying overlapping or adjacent habitat ranges with orangutans; in contrast, HBV variants from gibbon species in mainland Asia were phylogenetically distinct. A geographical rather than (sub)species association of HBV would account for the distribution of HBV variants in different subspecies of chimpanzees in Africa, and explain the inlier position of the previously described lowland gorilla sequence in the chimpanzee clade. These new findings have a number of implication for understanding the origins and epidemiology of HBV infection in non-human primates

  4. Protective potential of antioxidant enzymes as vaccines for schistosomiasis in a non-human primate model

    Directory of Open Access Journals (Sweden)

    Claudia eCarvalho-Queiroz

    2015-06-01

    Full Text Available 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. Recent large-scale efforts aimed at limiting schistosomiasis have produced 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 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. PBMC, mesenteric and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. These data demonstrate the potential of antioxidants as vaccine

  5. 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).

  6. [3H]cholesteryl ester labeling and transfer among human and honhuman primate plasma lipoproteins

    International Nuclear Information System (INIS)

    Thomas, M.S.; Rudel, L.L.

    1983-01-01

    Aliquots of human and nonhuman primate plasma containing 5,5'-dithiobis (2-nitrobenzoic acid) were incubated at 37 0 C in tubes previously coated with trace amounts of tritium-labeled cholesteryl oleate ([ 3 H]CO). Initially, cholesteryl esters were transferred at a rapid rate into plasma after which the rate slowed. During 24 h of incubation, an average of 55% of the [ 3 H]CO transferred from the side of the tube into African green monkey plasma, 44% into human plasma and 21% into rat plasma. Greater than 98% of the radioactive ester transferred into plasma was found to be associated with plasma lipoproteins that were then rapidly separated using vertical rotor density gradient ultracentrifugation. In very low density lipoprotein (VLDL)-poor plasma after 30 min incubations, high density lipoproteins (HDL) contained most of the [ 3 H]CO while 5- to 24-h incubations resulted in increased labeling of low density proteins (LDL). In VLDL-rich plasma, it was found that in addition to the labeling of HDL, VLDL contained about 25% of the labeled cholesteryl esters after 30-min incubations and, as above, the proportion in LDL subsequently increased. Compositional analyses showed that intermediate-sized LDL (ILDL) were accumulating cholesteryl ester mass while transfer occurred. LDL labeled using this method were injected intravenously into monkeys and their removal from plasma was found to be similar to that found for LDL labeled in vivo. It was concluded that this method of plasma lipoprotein cholesteryl ester labeling, presumably a result of cholesteryl ester transfer protein activity, was efficient, resulted in lipoproteins labeled only in the cholesteryl ester moiety, and induced minimal modification of lipoprotein particles that did not alter their biological activity

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Safety testing of monoclonal antibodies in non-human primates: Case studies highlighting their impact on human risk assessment.

    Science.gov (United States)

    Brennan, Frank R; Cavagnaro, Joy; McKeever, Kathleen; Ryan, Patricia C; Schutten, Melissa M; Vahle, John; Weinbauer, Gerhard F; Marrer-Berger, Estelle; Black, Lauren E

    2018-01-01

    Monoclonal antibodies (mAbs) are improving the quality of life for patients suffering from serious diseases due to their high specificity for their target and low potential for off-target toxicity. The toxicity of mAbs is primarily driven by their pharmacological activity, and therefore safety testing of these drugs prior to clinical testing is performed in species in which the mAb binds and engages the target to a similar extent to that anticipated in humans. For highly human-specific mAbs, this testing often requires the use of non-human primates (NHPs) as relevant species. It has been argued that the value of these NHP studies is limited because most of the adverse events can be predicted from the knowledge of the target, data from transgenic rodents or target-deficient humans, and other sources. However, many of the mAbs currently in development target novel pathways and may comprise novel scaffolds with multi-functional domains; hence, the pharmacological effects and potential safety risks are less predictable. Here, we present a total of 18 case studies, including some of these novel mAbs, with the aim of interrogating the value of NHP safety studies in human risk assessment. These studies have identified mAb candidate molecules and pharmacological pathways with severe safety risks, leading to candidate or target program termination, as well as highlighting that some pathways with theoretical safety concerns are amenable to safe modulation by mAbs. NHP studies have also informed the rational design of safer drug candidates suitable for human testing and informed human clinical trial design (route, dose and regimen, patient inclusion and exclusion criteria and safety monitoring), further protecting the safety of clinical trial participants.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. 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.

  11. COMT Val158 Met moderates the link between rank and aggression in a non-human primate.

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    Gutleb, D R; Roos, C; Noll, A; Ostner, J; Schülke, O

    2018-04-01

    The COMT Val 158 Met polymorphism is one of the most widely studied genetic polymorphisms in humans implicated in aggression and the moderation of stressful life event effects. We screened a wild primate population for polymorphisms at the COMT Val 158 Met site and phenotyped them for aggression to test whether the human polymorphism exists and is associated with variation in aggressive behavior. Subjects were all adults from 4 study groups (37 males, 40 females) of Assamese macaques (Macaca assamensis) in their natural habitat (Phu Khieo Wildlife Sanctuary, Thailand). We collected focal animal behavioral data (27 males, 36 females, 5964 focal hours) and fecal samples for non-invasive DNA analysis. We identified the human COMT Val 158 Met polymorphism (14 Met/Met, 41 Val/Met and 22 Val/Val). Preliminary results suggest that COMT genotype and dominance rank interact to influence aggression rates. Aggression rates increased with rank in Val/Val, but decreased in Met/Met and Val/Met individuals, with no significant main effect of COMT genotype on aggression. Further support for the interaction effect comes from time series analyses revealing that when changing from lower to higher rank position Val/Val individuals decreased, whereas Met/Met individuals increased their aggression rate. Contradicting the interpretation of earlier studies, we show that the widely studied Val 158 Met polymorphism in COMT is not unique to humans and yields similar behavioral phenotypes in a non-human primate. This study represents an important step towards understanding individual variation in aggression in a wild primate population and may inform human behavioral geneticists about the evolutionary roots of inter-individual variation in aggression. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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

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    Michaela D Curry

    2017-07-01

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

  13. Social complexity parallels vocal complexity: a comparison of three non-human primate species.

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    Bouchet, Hélène; Blois-Heulin, Catherine; Lemasson, Alban

    2013-01-01

    Social factors play a key role in the structuring of vocal repertoires at the individual level, notably in non-human primates. Some authors suggested that, at the species level too, social life may have driven the evolution of communicative complexity, but this has rarely been empirically tested. Here, we use a comparative approach to address this issue. We investigated vocal variability, at both the call type and the repertoire levels, in three forest-dwelling species of Cercopithecinae presenting striking differences in their social systems, in terms of social organization as well as social structure. We collected female call recordings from twelve De Brazza's monkeys (Cercopithecus neglectus), six Campbell's monkeys (Cercopithecus campbelli) and seven red-capped mangabeys (Cercocebus torquatus) housed in similar conditions. First, we noted that the level of acoustic variability and individual distinctiveness found in several call types was related to their importance in social functioning. Contact calls, essential to intra-group cohesion, were the most individually distinctive regardless of the species, while threat calls were more structurally variable in mangabeys, the most "despotic" of our three species. Second, we found a parallel between the degree of complexity of the species' social structure and the size, diversity, and usage of its vocal repertoire. Mangabeys (most complex social structure) called twice as often as guenons and displayed the largest and most complex repertoire. De Brazza's monkeys (simplest social structure) displayed the smallest and simplest repertoire. Campbell's monkeys displayed an intermediate pattern. Providing evidence of higher levels of vocal variability in species presenting a more complex social system, our results are in line with the theory of a social-vocal coevolution of communicative abilities, opening new perspectives for comparative research on the evolution of communication systems in different animal taxa.

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

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    Fernandez-Leon, Jose A; Parajuli, Arun; Franklin, Robert; Sorenson, Michael; Felleman, Daniel J; Hansen, Bryan J; Hu, Ming; Dragoi, Valentin

    2015-10-01

    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. 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. 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. 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. 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.

  16. Zinc bioavailability from legumes in non-human primates (Macaca fascicularis)

    International Nuclear Information System (INIS)

    Sockalingam, S.

    1984-01-01

    Zinc bioavailability from legumes in non-human primates (M. Fascicularis) was studied by: (1) determining zinc requirements of adolescent monkeys, (2) validating the use of extrinsic zinc label in peas, (3) validating the blood appearance and disappearance technique, and (4) measuring zinc absorption and endogenous excretion from control and legume diets. Ten monkeys were assigned to the control (CG) and legume groups (LG) based on their initial body weights and plasma zinc concentrations. Zinc salt or legumes served as the source of zinc for CG and LG, respectively. The animals were adapted for three weeks to 2.23, 5.70, 11.67, 16.70 and 30.00 ppm dietary zinc for the requirement and bioavailability experiments and 5.70 ppm dietary zinc for the extrinsic labeling study and the blood appearance and disappearance study. Zinc requirement was determined using the following criteria: body weight, clinical signs and plasma, leukocyte and erythrocyte zinc concentrations. The use of the extrinsic label was validated by comparing percent absorption of 65 Zn (salt) and intrinsically labeled 65 Zn from peas. The blood appearance and disappearance of orally administered /sup 69m/Zn (CG) and 65 Zn(LG) and intravenously administered 65 Zn was determined serially in blood over an eight hour period. Zinc absorption and regulation in the CG and LG was determined by the fecal balance method and endogenous excretion of intravenously administered 65 Zn. The zinc requirement for adolescent M. Fascicularis was between 11.67 and 16.70 ppm dietary zinc per day

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

    Science.gov (United States)

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

    2014-01-01

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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Krista Geraldine Haanstra

    2016-11-01

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

  20. Reciprocity explains food sharing in humans and other primates independent of kin selection and tolerated scrounging: a phylogenetic meta-analysis.

    Science.gov (United States)

    Jaeggi, Adrian V; Gurven, Michael

    2013-10-07

    Helping, i.e. behaviour increasing the fitness of others, can evolve when directed towards kin or reciprocating partners. These predictions have been tested in the context of food sharing both in human foragers and non-human primates. Here, we performed quantitative meta-analyses on 32 independent study populations to (i) test for overall effects of reciprocity on food sharing while controlling for alternative explanations, methodological biases, publication bias and phylogeny and (ii) compare the relative effects of reciprocity, kinship and tolerated scrounging, i.e. sharing owing to costs imposed by others. We found a significant overall weighted effect size for reciprocity of r = 0.20-0.48 for the most and least conservative measure, respectively. Effect sizes did not differ between humans and other primates, although there were species differences in in-kind reciprocity and trade. The relative effect of reciprocity in sharing was similar to those of kinship and tolerated scrounging. These results indicate a significant independent contribution of reciprocity to human and primate helping behaviour. Furthermore, similar effect sizes in humans and primates speak against cognitive constraints on reciprocity. This study is the first to use meta-analyses to quantify these effects on human helping and to directly compare humans and other primates.

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

    Science.gov (United States)

    Naidoo-Variawa, S.; Hey-Cunningham, A. J.; Lehnert, W.; Kench, P. L.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2007-11-01

    The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm3 FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm3) and 3D reprojection (3DRP) (5.9-9.1 mm3). A pilot 18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

  2. 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.

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

    Science.gov (United States)

    Fourie, Nicolaas H; Brown, Janine L; Jolly, Clifford J; Phillips-Conroy, Jane E; Rogers, Jeffrey; Bernstein, Robin M

    2016-04-01

    Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results. Published by Elsevier GmbH.

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

    Science.gov (United States)

    Emery Thompson, Melissa

    2017-05-01

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

  5. Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research.

    Science.gov (United States)

    Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R

    2018-03-01

    Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely

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

    Science.gov (United States)

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

    2014-11-01

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

  7. Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Jacqueline R. Thompson

    2018-04-01

    Full Text Available Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD, metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2017-01-01

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

  10. The carcinogenic risk of high dose total body irradiation in non-human primates

    International Nuclear Information System (INIS)

    Broerse, J.J.; Bartstra, R.W.; Bekkum, D.W. van; Hage, M.H. van der; Zurcher, C.; Zwieten, M.J. van; Hollander, C.F.

    2000-01-01

    High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on turnout induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older a-e compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcormas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a

  11. 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

  12. A molecular phylogeny of living primates.

    Science.gov (United States)

    Perelman, Polina; Johnson, Warren E; Roos, Christian; Seuánez, Hector N; Horvath, Julie E; Moreira, Miguel A M; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C; Silva, Artur; O'Brien, Stephen J; Pecon-Slattery, Jill

    2011-03-01

    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

  13. A Molecular Phylogeny of Living Primates

    Science.gov (United States)

    Perelman, Polina; Johnson, Warren E.; Roos, Christian; Seuánez, Hector N.; Horvath, Julie E.; Moreira, Miguel A. M.; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C.; Silva, Artur; O'Brien, Stephen J.; Pecon-Slattery, Jill

    2011-01-01

    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (∼8 Mb) from 186 primates representing 61 (∼90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species. PMID:21436896

  14. A molecular phylogeny of living primates.

    Directory of Open Access Journals (Sweden)

    Polina Perelman

    2011-03-01

    Full Text Available Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb from 186 primates representing 61 (~90% of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

  15. Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin.

    Science.gov (United States)

    Mueller, Kate R; Balamurugan, A N; Cline, Gary W; Pongratz, Rebecca L; Hooper, Rebecca L; Weegman, Bradley P; Kitzmann, Jennifer P; Taylor, Michael J; Graham, Melanie L; Schuurman, Henk-Jan; Papas, Klearchos K

    2013-01-01

    Porcine islet xenotransplantation is considered a potential cell-based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics of islets, the suitability and predictive value of the preclinical model in the extrapolation to the clinical setting remain a critical issue. Islets isolated from human (n = 3), NHP (n = 2), adult pig (AP, n = 3), and juvenile pig (JP, n = 4) pancreata were perifused with medium at basal glucose (2.5 mm) followed by high glucose (16.7 mm) concentrations. The total glucose-stimulated insulin secretion (GSIS) was calculated from generated insulin secretion profiles. Nonhuman primate islets exhibited GSIS 3-fold higher than AP islets, while AP and JP islets exhibited GSIS 1/3 and 1/30 of human islets, respectively. The insulin content of NHP and AP islets was similar to that of human islets, whereas that of JP islets was 1/5 of human islets. Despite the fact that human, NHP, and AP islets contain similar amounts of insulin, the much higher GSIS for NHP islets than for AP and JP islets suggests the need for increased dosing of islets from JP and AP in pig-to-NHP transplantation. Porcine islet xenotransplantation to humans may require significantly higher dosing given the lower GSIS of AP islets compared to human islets. © 2013 John Wiley & Sons A/S.

  16. The monitoring and control of task sequences in human and non-human primates

    Directory of Open Access Journals (Sweden)

    Theresa M Desrochers

    2016-01-01

    Full Text Available Our ability to plan and execute a series of tasks leading to a desired goal requires remarkable coordination between sensory, motor, and decision-related systems. Prefrontal cortex is thought to play a central role in this coordination, especially when actions must be assembled extemporaneously and cannot be programmed as a rote series of movements. A central component of this flexible behavior is the moment-by-moment allocation of working memory and attention. The ubiquity of sequence planning in our everyday lives belies the neural complexity that supports this capacity, and little is known about how frontal cortical regions orchestrate the monitoring and control of sequential behaviors. For example, it remains unclear if and how sensory cortical areas, which provide essential driving inputs for behavior, are modulated by the frontal cortex during these tasks. Here we review what is known about moment-to-moment monitoring as it relates to visually guided, rule-driven behaviors that change over time. We highlight recent human work that shows how the rostrolateral prefrontal cortex (RLPFC participates in monitoring during task sequences. Neurophysiological data from monkeys suggests that monitoring may be accomplished by neurons that respond to items within the sequence and may in turn influence the tuning properties of neurons in posterior sensory areas. Understanding the interplay between proceduralized or habitual acts and supervised control of sequences is key to our understanding of sequential task execution. A crucial bridge will be the use of experimental protocols that allow for the examination of the functional homology between monkeys and humans. We illustrate how task sequences may be parceled into components and examined experimentally, thereby opening future avenues of investigation into the neural basis of sequential monitoring and control.

  17. Human grooming in comparative perspective: People in six small-scale societies groom less but socialize just as much as expected for a typical primate.

    Science.gov (United States)

    Jaeggi, Adrian V; Kramer, Karen L; Hames, Raymond; Kiely, Evan J; Gomes, Cristina; Kaplan, Hillard; Gurven, Michael

    2017-04-01

    Grooming has important utilitarian and social functions in primates but little is known about grooming and its functional analogues in traditional human societies. We compare human grooming to typical primate patterns to test its hygienic and social functions. Bayesian phylogenetic analyses were used to derive expected human grooming time given the potential associations between grooming, group size, body size, terrestriality, and several climatic variables across 69 primate species. This was compared against observed times dedicated to grooming, other hygienic behavior, and conversation among the Maya, Pumé, Sanöma, Tsimane', Yanomamö, and Ye'kwana (mean number of behavioral scans = 23,514). Expected grooming time for humans was 4% (95% Credible Interval = 0.07%-14%), similar to values observed in primates, based largely on terrestriality and phylogenetic signal (mean λ = 0.56). No other covariates strongly associated with grooming across primates. Observed grooming time across societies was 0.8%, lower than 89% of the expected values. However, the observed times dedicated to any hygienic behavior (3.0%) or "vocal grooming," that is conversation (7.3%), fell within the expected range. We found (i) that human grooming may be a (recent) phylogenetic outlier when defined narrowly as parasite removal but not defined broadly as personal hygiene, (ii) there was no support for thermoregulatory functions of grooming, and (iii) no support for the "vocal grooming" hypothesis of language having evolved as a less time-consuming means of bonding. Thus, human grooming reflects decreased hygienic needs, but similar social needs compared to primate grooming. © 2017 Wiley Periodicals, Inc.

  18. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Michel Modo

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

  19. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

    Science.gov (United States)

    Modo, Michel; Crum, William R; Gerwig, Madeline; Vernon, Anthony C; Patel, Priya; Jackson, Michael J; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud M

    2017-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    a significant positive correlation with protection at week 6 post infection, whereas the opposite was observed for post infection CD4 T cells producing only IFN-γ. Moreover, as a BCG booster vaccine in a clinically relevant non-human primate TB model, the H28/H28 vaccine strategy induced a slightly more......-γ single producing CD4 T cell subsets correlated with protection in the mouse TB model. Moreover, our data demonstrated that the H28 vaccine antigen was able to induce strong protection in both a mouse and a non-human primate TB model....

  1. Occurrence and distribution of Indian primates

    Science.gov (United States)

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

    2010-01-01

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

  2. Novel polyomaviruses of nonhuman primates: genetic and serological predictors for the existence of multiple unknown polyomaviruses within the human population.

    Directory of Open Access Journals (Sweden)

    Nelly Scuda

    Full Text Available Polyomaviruses are a family of small non-enveloped DNA viruses that encode oncogenes and have been associated, to greater or lesser extent, with human disease and cancer. Currently, twelve polyomaviruses are known to circulate within the human population. To further examine the diversity of human polyomaviruses, we have utilized a combinatorial approach comprised of initial degenerate primer-based PCR identification and phylogenetic analysis of nonhuman primate (NHP polyomavirus species, followed by polyomavirus-specific serological analysis of human sera. Using this approach we identified twenty novel NHP polyomaviruses: nine in great apes (six in chimpanzees, two in gorillas and one in orangutan, five in Old World monkeys and six in New World monkeys. Phylogenetic analysis indicated that only four of the nine chimpanzee polyomaviruses (six novel and three previously identified had known close human counterparts. To determine whether the remaining chimpanzee polyomaviruses had potential human counterparts, the major viral capsid proteins (VP1 of four chimpanzee polyomaviruses were expressed in E. coli for use as antigens in enzyme-linked immunoassay (ELISA. Human serum/plasma samples from both Côte d'Ivoire and Germany showed frequent seropositivity for the four viruses. Antibody pre-adsorption-based ELISA excluded the possibility that reactivities resulted from binding to known human polyomaviruses. Together, these results support the existence of additional polyomaviruses circulating within the human population that are genetically and serologically related to existing chimpanzee polyomaviruses.

  3. Novel Polyomaviruses of Nonhuman Primates: Genetic and Serological Predictors for the Existence of Multiple Unknown Polyomaviruses within the Human Population

    Science.gov (United States)

    Scuda, Nelly; Madinda, Nadege Freda; Akoua-Koffi, Chantal; Adjogoua, Edgard Valerie; Wevers, Diana; Hofmann, Jörg; Cameron, Kenneth N.; Leendertz, Siv Aina J.; Couacy-Hymann, Emmanuel; Robbins, Martha; Boesch, Christophe; Jarvis, Michael A.; Moens, Ugo; Mugisha, Lawrence; Calvignac-Spencer, Sébastien; Leendertz, Fabian H.; Ehlers, Bernhard

    2013-01-01

    Polyomaviruses are a family of small non-enveloped DNA viruses that encode oncogenes and have been associated, to greater or lesser extent, with human disease and cancer. Currently, twelve polyomaviruses are known to circulate within the human population. To further examine the diversity of human polyomaviruses, we have utilized a combinatorial approach comprised of initial degenerate primer-based PCR identification and phylogenetic analysis of nonhuman primate (NHP) polyomavirus species, followed by polyomavirus-specific serological analysis of human sera. Using this approach we identified twenty novel NHP polyomaviruses: nine in great apes (six in chimpanzees, two in gorillas and one in orangutan), five in Old World monkeys and six in New World monkeys. Phylogenetic analysis indicated that only four of the nine chimpanzee polyomaviruses (six novel and three previously identified) had known close human counterparts. To determine whether the remaining chimpanzee polyomaviruses had potential human counterparts, the major viral capsid proteins (VP1) of four chimpanzee polyomaviruses were expressed in E. coli for use as antigens in enzyme-linked immunoassay (ELISA). Human serum/plasma samples from both Côte d'Ivoire and Germany showed frequent seropositivity for the four viruses. Antibody pre-adsorption-based ELISA excluded the possibility that reactivities resulted from binding to known human polyomaviruses. Together, these results support the existence of additional polyomaviruses circulating within the human population that are genetically and serologically related to existing chimpanzee polyomaviruses. PMID:23818846

  4. ELFN1-AS1: A Novel Primate Gene with Possible MicroRNA Function Expressed Predominantly in Human Tumors

    Directory of Open Access Journals (Sweden)

    Dmitrii E. Polev

    2014-01-01

    Full Text Available Human gene LOC100505644 uncharacterized LOC100505644 [Homo sapiens] (Entrez Gene ID 100505644 is abundantly expressed in tumors but weakly expressed in few normal tissues. Till now the function of this gene remains unknown. Here we identified the chromosomal borders of the transcribed region and the major splice form of the LOC100505644-specific transcript. We characterised the major regulatory motifs of the gene and its splice sites. Analysis of the secondary structure of the major transcript variant revealed a hairpin-like structure characteristic for precursor microRNAs. Comparative genomic analysis of the locus showed that it originated in primates de novo. Taken together, our data indicate that human gene LOC100505644 encodes some non-protein coding RNA, likely a microRNA. It was assigned a gene symbol ELFN1-AS1 (ELFN1 antisense RNA 1 (non-protein coding. This gene combines features of evolutionary novelty and predominant expression in tumors.

  5. The appropriation of glucose through primate neurodevelopment.

    Science.gov (United States)

    Bauernfeind, Amy L; Babbitt, Courtney C

    2014-12-01

    The human brain is considerably larger and more energetically costly than that of other primate species. As such, discovering how human ancestors were able to provide sufficient energy to their brains is a central theme in the study of hominin evolution. However, many discussions of metabolism frequently omit the different ways in which energy, primarily glucose, is used once made available to the brain. In this review, we discuss two glucose metabolic pathways, oxidative phosphorylation and aerobic glycolysis, and their respective contributions to the energetic and anabolic budgets of the brain. While oxidative phosphorylation is a more efficient producer of energy, aerobic glycolysis contributes essential molecules for the growth of the brain and maintaining the structure of its cells. Although both pathways occur in the brain throughout the lifetime, aerobic glycolysis is a critical pathway during development, and oxidative phosphorylation is highest during adulthood. We outline how elevated levels of aerobic glycolysis may support the protracted neurodevelopmental sequence of humans compared with other primates. Finally, we review the genetic evidence for differences in metabolic function in the brains of primates and explore genes that may provide insight into how glucose metabolism may differ across species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Dopamine-dependent social information processing in non-human primates.

    Science.gov (United States)

    Lee, Young-A; Lionnet, Sarah; Kato, Akemi; Goto, Yukiori

    2018-04-01

    Dopamine (DA) is a neurotransmitter whose roles have been suggested in various aspects of brain functions. Recent studies in rodents have reported its roles in social function. However, how DA is involved in social information processing in primates has largely remained unclear. We investigated prefrontal cortical (PFC) activities associated with social vs. nonsocial visual stimulus processing. Near-infrared spectroscopy (NIRS) was applied to Japanese macaques, along with pharmacological manipulations of DA transmission, while they were gazing at social and nonsocial visual stimuli. Oxygenated (oxy-Hb) and deoxygenated (deoxy-Hb) hemoglobin changes as well as functional connectivity based on such Hb changes within the PFC network which were distinct between social and nonsocial stimuli were observed. Administration of both D1 and D2 receptor antagonists affected the Hb changes associated with social stimuli, whereas D1, but not D2, receptor antagonist affected the Hb changes associated with nonsocial stimuli. These results suggest that mesocortical DA transmission in the PFC plays significant roles in social information processing, which involves both D1 and D2 receptor activation, in nonhuman primates. However, D1 and D2 receptor signaling in the PFC mediates different aspects of social vs. nonsocial information processing.

  7. Reproductive cloning in humans and therapeutic cloning in primates: is the ethical debate catching up with the recent scientific advances?

    Science.gov (United States)

    Camporesi, S; Bortolotti, L

    2008-09-01

    After years of failure, in November 2007 primate embryonic stem cells were derived by somatic cellular nuclear transfer, also known as therapeutic cloning. The first embryo transfer for human reproductive cloning purposes was also attempted in 2006, albeit with negative results. These two events force us to think carefully about the possibility of human cloning which is now much closer to becoming a reality. In this paper we tackle this issue from two sides, first summarising what scientists have achieved so far, then discussing some of the ethical arguments in favour and against human cloning which are debated in the context of policy making and public consultation. Therapeutic cloning as a means to improve and save lives has uncontroversial moral value. As to human reproductive cloning, we consider and assess some common objections and failing to see them as conclusive. We do recognise, though, that there will be problems at the level of policy and regulation that might either impair the implementation of human reproductive cloning or make its accessibility restricted in a way that could become difficult to justify on moral grounds. We suggest using the time still available before human reproductive cloning is attempted successfully to create policies and institutions that can offer clear directives on its legitimate applications on the basis of solid arguments, coherent moral principles, and extensive public consultation.

  8. 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.

  9. 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.

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

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    Anisur Rahman

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

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

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    Sirigu, Angela; Duhamel, Jean-René

    2016-03-01

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

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

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    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. © 2015 The Author(s).

  13. Inter-individual relationships in proboscis monkeys: a preliminary comparison with other non-human primates.

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    Matsuda, Ikki; Tuuga, Augustine; Bernard, Henry; Furuichi, Takeshi

    2012-01-01

    This is the first report on inter-individual relationships within a one-male group of proboscis monkeys (Nasalis larvatus) based on detailed identification of individuals. From May 2005 to 2006, focal and ad libitum data of agonistic and grooming behaviour were collected in a forest along the Menanggul River, Sabah, Malaysia. During the study period, we collected over 1,968 h of focal data on the adult male and 1,539 h of focal data on the six females. Their social interactions, including agonistic and grooming behaviour, appeared to follow typical patterns reported for other colobines: the incidence of social interaction within groups is low. Of 39 agonistic events, 26 were displacement from sleeping places along the river, 6 were the α male threatening other monkeys to mediate quarrels between females and between females and juveniles, and 7 were displacement from feeding places. Although the agonistic behaviour matrix based on the 33 intra-group agonistic events (excluding events between adults and juveniles and between adults and infants) was indicative of non-significant linearity, there were some specific dominated individuals within the group of proboscis monkeys. Nonetheless, grooming behaviour among adult females within a group were not affected by the dominance hierarchy. This study also conducted initial comparisons of grooming patterns among proboscis monkeys and other primate species. On the basis of comparison of their grooming networks, similar grooming patterns among both-sex-disperse and male-philopatric/female-disperse species were detected. Because adult females in these species migrate to groups repeatedly, it may be difficult to establish the firm grooming exchange relationship for particular individuals within groups, unlike in female-philopatric/male-disperse species. However, grooming distribution patterns within groups among primate species were difficult to explain solely on the basis of their dispersal patterns. Newly immigrated females

  14. Inducible nitric oxide synthase (iNOS) regulatory region variation in non-human primates.

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    Roodgar, Morteza; Ross, Cody T; Kenyon, Nicholas J; Marcelino, Gretchen; Smith, David Glenn

    2015-04-01

    Inducible nitric oxide synthase (iNOS) is an enzyme that plays a key role in intracellular immune response against respiratory infections. Since various species of nonhuman primates exhibit different levels of susceptibility to infectious respiratory diseases, and since variation in regulatory regions of genes is thought to play a key role in expression levels of genes, two candidate regulatory regions of iNOS were mapped, sequenced, and compared across five species of nonhuman primates: African green monkeys (Chlorocebus sabaeus), pig-tailed macaques (Macaca nemestrina), cynomolgus macaques (Macaca fascicularis), Indian rhesus macaques (Macaca mulatta), and Chinese rhesus macaques (M. mulatta). In addition, we conducted an in silico analysis of the transcription factor binding sites associated with genetic variation in these two candidate regulatory regions across species. We found that only one of the two candidate regions showed strong evidence of involvement in iNOS regulation. Specifically, we found evidence of 13 conserved binding site candidates linked to iNOS regulation: AP-1, C/EBPB, CREB, GATA-1, GATA-3, NF-AT, NF-AT5, NF-κB, KLF4, Oct-1, PEA3, SMAD3, and TCF11. Additionally, we found evidence of interspecies variation in binding sites for several regulatory elements linked to iNOS (GATA-3, GATA-4, KLF6, SRF, STAT-1, STAT-3, OLF-1 and HIF-1) across species, especially in African green monkeys relative to other species. Given the key role of iNOS in respiratory immune response, the findings of this study might help guide the direction of future studies aimed to uncover the molecular mechanisms underlying the increased susceptibility of African green monkeys to several viral and bacterial respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Neuroendocrine control in social relationships in non-human primates: Field based evidence.

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    Ziegler, Toni E; Crockford, Catherine

    2017-05-01

    Primates maintain a variety of social relationships and these can have fitness consequences. Research has established that different types of social relationships are unpinned by different or interacting hormonal systems, for example, the neuropeptide oxytocin influences social bonding, the steroid hormone testosterone influences dominance relationships, and paternal care is characterized by high oxytocin and low testosterone. Although the oxytocinergic system influences social bonding, it can support different types of social bonds in different species, whether pair bonds, parent-offspring bonds or friendships. It seems that selection processes shape social and mating systems and their interactions with neuroendocrine pathways. Within species, there are individual differences in the development of the neuroendocrine system: the social environment individuals are exposed to during ontogeny alters their neuroendocrine and socio-cognitive development, and later, their social interactions as adults. Within individuals, neuroendocrine systems can also have short-term effects, impacting on social interactions, such as those during hunting, intergroup encounters or food sharing, or the likelihood of cooperating, winning or losing. To understand these highly dynamic processes, extending research beyond animals in laboratory settings to wild animals living within their natural social and ecological setting may bring insights that are otherwise unreachable. Field endocrinology with neuropeptides is still emerging. We review the current status of this research, informed by laboratory studies, and identify questions particularly suited to future field studies. We focus on primate social relationships, specifically social bonds (mother-offspring, father-offspring, cooperative breeders, pair bonds and adult platonic friendships), dominance, cooperation and in-group/out-group relationships, and examine evidence with respect to the 'tend and defend' hypothesis. Copyright © 2017

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

    Science.gov (United States)

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

    2015-06-01

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

  17. 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

  18. 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.

  19. Links between the discovery of primates and anatomical comparisons with humans, the chain of being, our place in nature, and racism.

    Science.gov (United States)

    Diogo, Rui

    2018-04-01

    I focus on the crucial links between the discovery of nonhuman primates by Westerners, discussions on our place in nature, the chain of being, racism, and the history of primate comparative anatomy and of so-called "anatomical human racial studies." Strikingly, for more than a millennium humans knew more about the internal anatomy of a single monkey species than about that of their own bodies. This is because Galen used monkeys to infer human anatomy, in line with the human-animal continuity implied by the Greek notion of scala naturae. With the rise of Christianity, nonhuman primates were increasingly seen in a negative way. A more positive view emerged in the 14th century when nonhuman primates were directly studied/seen by Europeans, culminating in Tyson's 1699 work showing that chimps share more gross anatomical similarities with humans than with monkeys. However, the discomfort caused by this human-chimp similarity then led to a new idea of animal-human discontinuity, now related not to anatomy but to "civilization": between Europeans vs. non-Europeans + other primates. Moreover, Linnaeus' Systema Naturae and the emergence of "anatomical racial studies" influenced by Camper's craniology then led to even more extreme ideas, such as the notion that Europeans were both mentally and morphologically "ideal." Unfortunately the biased and often incorrect "results" of such studies, combined with ideas based on Darwin's "struggle for survival", became crucial in propaganda that lead to the rise of eugenics in the end of the 19th/first half of 20th centuries and that culminated in Nazism. Since the 1950s there has been an emphasis on the continuity/unity between all human groups and other primates, in great part influenced by what happened during World War 2. Reviews such as this one are, therefore, particularly necessary to illuminate and guard against attitudes against "the Other" and racist ideologies that are re-emerging in modern political discourse across the

  20. 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.

  1. Interpreting sex differences in enamel hypoplasia in human and non-human primates: Developmental, environmental, and cultural considerations.

    Science.gov (United States)

    Guatelli-Steinberg, D; Lukacs, J R

    1999-01-01

    The purpose of this review is to provide a synoptic, critical evaluation of the evidence of, and potential etiological factors contributing to, sex differences in the expression of enamel hypoplasia (EH). Specifically, this review considers theoretical expectations and empirical evidence bearing on two central issues. The first of these is the impact of a theorized inherent male vulnerability to physiological stress on sex differences in EH. The second issue is the potential contribution to sex differences in EH of intrinsic differences in male and female enamel composition and development. To address this first issue, EH frequencies by sex are examined in samples subject to a high degree of physiological stress. Based on the concept of inherent male vulnerability (or female buffering), males in stressful environments would be expected to exhibit higher EH frequencies than females. This expectation is evaluated in light of cultural practices of sex-biased investment that mediate the relationship between environmental stress and EH expression. Defects forming prenatally afford an opportunity to study this relationship without the confounding effects of sex-biased postnatal investment. Data bearing on this issue derive from previously conducted studies of EH in permanent and deciduous teeth in both modern and archaeological samples as well as from new data on Indian schoolchildren. To address the second issue, fundamental male-female enamel differences are evaluated for their potential impact on EH expression. A large sex difference in the duration of canine crown formation in non-human primates suggests that male canines may have greater opportunity to record stress events than those of females. This expectation is examined in great apes, whose canines often record multiple episodes of stress and are sexually dimorphic in crown formation times. With respect to the first issue, in most studies, sex differences in EH prevalence are statistically nonsignificant

  2. Recombinant human parainfluenza virus type 2 with mutations in V that permit cellular interferon signaling are not attenuated in non-human primates

    Science.gov (United States)

    Schaap-Nutt, Anne; D’Angelo, Christopher; Amaro-Carambot, Emerito; Nolan, Sheila M.; Davis, Stephanie; Wise, Shenelle-Marie; Higgins, Caraline; Bradley, Konrad; Kim, Olivia; Mayor, Reina; Skiadopoulos, Mario H.; Collins, Peter L.; Murphy, Brian R.; Schmidt, Alexander C.

    2010-01-01

    The HPIV2 V protein inhibits type I interferon (IFN) induction and signaling. To manipulate the V protein, whose coding sequence overlaps that of the polymerase-associated phosphoprotein (P), without altering the P protein, we generated an HPIV2 virus in which P and V are expressed from separate genes (rHPIV2-P+V). rHPIV2-P+V replicated like HPIV2-WT in vitro and in non-human primates. HPIV2-P+V was modified by introducing two separate mutations into the V protein to create rHPIV2-L101E/L102E and rHPIV2-Δ122–127. In contrast to HPIV2-WT, both mutant viruses were unable to degrade STAT2, leaving virus-infected cells susceptible to IFN. Neither mutant, nor HPIV2-WT, induced significant amounts of IFN-β in infected cells. Surprisingly, neither rHPIV2-L101E/L102E nor rHPIV2-Δ122–127 was attenuated in two species of non-human primates. This indicates that loss of HPIV2's ability to inhibit IFN signaling is insufficient to attenuate virus replication in vivo as long as IFN induction is still inhibited. PMID:20667570

  3. Rabies in Nonhuman Primates and Potential for Transmission to Humans: A Literature Review and Examination of Selected French National Data

    Science.gov (United States)

    Gautret, Philippe; Blanton, Jesse; Dacheux, Laurent; Ribadeau-Dumas, Florence; Brouqui, Philippe; Parola, Philippe; Esposito, Douglas H.; Bourhy, Hervé

    2014-01-01

    Background The nonhuman primate (NHP)-related injuries in rabies-enzootic countries is a public health problem of increasing importance. The aims of this work are to collect data concerning rabies transmission from NHPs to humans; to collate medical practices regarding rabies postexposure prophylaxis (PEP) in different countries, and to provide an evidence base to support the decision to apply rabies PEP in this context. Methodology To retrieve information, we conducted a literature search from 1960 to January 2013. All reports of rabies in NHPs and rabies transmission to humans by infected NHPs were included. Also included were studies of travelers seeking care for rabies PEP in various settings. Data collected by the French National Reference Centre for Rabies concerning NHPs submitted for rabies diagnosis in France and human rabies exposure to NHPs in travelers returning to France were analyzed for the periods 1999–2012 and 1994–2011, respectively. Principal findings A total of 159 reports of rabies in NHPs have been retrieved from various sources in South America, Africa, and Asia, including 13 cases in animals imported to Europe and the US. 134 were laboratory confirmed cases. 25 cases of human rabies following NHP-related injuries were reported, including 20 from Brazil. Among more than 2000 international travelers from various settings, the proportion of injuries related to NHP exposures was about 31%. NHPs rank second, following dogs in most studies and first in studies conducted in travelers returning from Southeast Asia. In France, 15.6% of 1606 travelers seeking PEP for exposure to any animal were injured by monkeys. Conclusions/significance Although less frequently reported in published literature than human rabies, confirmed rabies cases in NHPs occur. The occurrence of documented transmission of rabies from NHPs to human suggests that rabies PEP is indicated in patients injured by NHPs in rabies-enzootic countries. PMID:24831694

  4. Rabies in nonhuman primates and potential for transmission to humans: a literature review and examination of selected French national data.

    Directory of Open Access Journals (Sweden)

    Philippe Gautret

    2014-05-01

    Full Text Available BACKGROUND: The nonhuman primate (NHP-related injuries in rabies-enzootic countries is a public health problem of increasing importance. The aims of this work are to collect data concerning rabies transmission from NHPs to humans; to collate medical practices regarding rabies postexposure prophylaxis (PEP in different countries, and to provide an evidence base to support the decision to apply rabies PEP in this context. METHODOLOGY: To retrieve information, we conducted a literature search from 1960 to January 2013. All reports of rabies in NHPs and rabies transmission to humans by infected NHPs were included. Also included were studies of travelers seeking care for rabies PEP in various settings. Data collected by the French National Reference Centre for Rabies concerning NHPs submitted for rabies diagnosis in France and human rabies exposure to NHPs in travelers returning to France were analyzed for the periods 1999-2012 and 1994-2011, respectively. PRINCIPAL FINDINGS: A total of 159 reports of rabies in NHPs have been retrieved from various sources in South America, Africa, and Asia, including 13 cases in animals imported to Europe and the US. 134 were laboratory confirmed cases. 25 cases of human rabies following NHP-related injuries were reported, including 20 from Brazil. Among more than 2000 international travelers from various settings, the proportion of injuries related to NHP exposures was about 31%. NHPs rank second, following dogs in most studies and first in studies conducted in travelers returning from Southeast Asia. In France, 15.6% of 1606 travelers seeking PEP for exposure to any animal were injured by monkeys. CONCLUSIONS/SIGNIFICANCE: Although less frequently reported in published literature than human rabies, confirmed rabies cases in NHPs occur. The occurrence of documented transmission of rabies from NHPs to human suggests that rabies PEP is indicated in patients injured by NHPs in rabies-enzootic countries.

  5. Identifying recombinants in human and primate immunodeficiency virus sequence alignments using quartet scanning

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    Martin Darren P

    2009-04-01

    Full Text Available Abstract Background Recombination has a profound impact on the evolution of viruses, but characterizing recombination patterns in molecular sequences remains a challenging endeavor. Despite its importance in molecular evolutionary studies, identifying the sequences that exhibit such patterns has received comparatively less attention in the recombination detection framework. Here, we extend a quartet-mapping based recombination detection method to enable identification of recombinant sequences without prior specifications of either query and reference sequences. Through simulations we evaluate different recombinant identification statistics and significance tests. We compare the quartet approach with triplet-based methods that employ additional heuristic tests to identify parental and recombinant sequences. Results Analysis of phylogenetic simulations reveal that identifying the descendents of relatively old recombination events is a challenging task for all methods available, and that quartet scanning performs relatively well compared to the triplet based methods. The use of quartet scanning is further demonstrated by analyzing both well-established and putative HIV-1 recombinant strains. In agreement with recent findings, we provide evidence that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas the presumed parental lineage subtype G has a recombinant origin. We also demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in chimpanzees and further disentangle the recombinant history of SIV lineages in a primate immunodeficiency virus data set. Conclusion Quartet scanning makes a valuable addition to triplet-based methods for identifying recombinant sequences without prior specifications of either query and reference sequences. The new method is available in the VisRD v.3.0 package http://www.cmp.uea.ac.uk/~vlm/visrd.

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

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    Zhijun Zhong

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

  7. Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

    Science.gov (United States)

    Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

    2015-11-01

    Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

  8. Modeling H-ARS using hematological parameters: a comparison between the non-human primate and mini-pig

    International Nuclear Information System (INIS)

    Bolduc, David L.; Buenger, Rolf; Moroni, Maria; Blakely, William F.

    2016-01-01

    Multiple hematological biomarkers (i.e. complete blood counts and serum chemistry parameters) were used in a multivariate linear-regression fit to create predictive algorithms for estimating the severity of hematopoietic acute radiation syndrome (H-ARS) using two different species (i.e. Goettingen Mini-pig and non-human primate (NHP) (Macacca mulatta)). Biomarker data were analyzed prior to irradiation and between 1-60 days (mini-pig) and 1-30 days (NHP) after irradiation exposures of 1.6-3.5 Gy (mini-pig) and 6.5 Gy (NHP) 60 Co gamma ray doses at 0.5-0.6 Gy min -1 and 0.4 Gy min -1 , respectively. Fitted radiation risk and injury categorization (RRIC) values and RRIC prediction percent accuracies were compared between the two models. Both models estimated H-ARS severity with over 80% overall predictive power and with receiver operating characteristic curve area values of 0.884 and 0.825. These results based on two animal radiation models support the concept for the use of a hematopoietic-based algorithm for predicting the risk of H-ARS in humans. (authors)

  9. The ten-thousand year fever: rethinking human and wild primate malarias

    National Research Council Canada - National Science Library

    Cormier, Loretta A

    2011-01-01

    ... relationships between culture and environment that shape the trajectory of a parasite. She argues against the entrenched distinction between human and non-human malarias, using ethnoprimatology to develop a new understanding of cross-species exchange...

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

    Directory of Open Access Journals (Sweden)

    Marco A B Almeida

    2014-03-01

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

  11. Life stage differences in mammary gland gene expression profile in non-human primates.

    Science.gov (United States)

    Stute, Petra; Sielker, Sonja; Wood, Charles E; Register, Thomas C; Lees, Cynthia J; Dewi, Fitriya N; Williams, J Koudy; Wagner, Janice D; Stefenelli, Ulrich; Cline, J Mark

    2012-06-01

    Breast cancer (BC) is the most common malignancy of women in the developed world. To better understand its pathogenesis, knowledge of normal breast development is crucial, as BC is the result of disregulation of physiologic processes. The aim of this study was to investigate the impact of reproductive life stages on the transcriptional profile of the mammary gland in a primate model. Comparative transcriptomic analyses were carried out using breast tissues from 28 female cynomolgus macaques (Macaca fascicularis) at the following life stages: prepubertal (n = 5), adolescent (n = 4), adult luteal (n = 5), pregnant (n = 6), lactating (n = 3), and postmenopausal (n = 5). Mammary gland RNA was hybridized to Affymetrix GeneChip(®) Rhesus Macaque Genome Arrays. Differential gene expression was analyzed using ANOVA and cluster analysis. Hierarchical cluster analysis revealed distinct separation of life stage groups. More than 2,225 differentially expressed mRNAs were identified. Gene families or pathways that changed across life stages included those related to estrogen and androgen (ESR1, PGR, TFF1, GREB1, AR, 17HSDB2, 17HSDB7, STS, HSD11B1, AKR1C4), prolactin (PRLR, ELF5, STAT5, CSN1S1), insulin-like growth factor signaling (IGF1, IGFBP1, IGFBP5), extracellular matrix (POSTN, TGFB1, COL5A2, COL12A1, FOXC1, LAMC1, PDGFRA, TGFB2), and differentiation (CD24, CD29, CD44, CD61, ALDH1, BRCA1, FOXA1, POSTN, DICER1, LIG4, KLF4, NOTCH2, RIF1, BMPR1A, TGFB2). Pregnancy and lactation displayed distinct patterns of gene expression. ESR1 and IGF1 were significantly higher in the adolescent compared to the adult animals, whereas differentiation pathways were overrepresented in adult animals and pregnancy-associated life stages. Few individual genes were distinctly different in postmenopausal animals. Our data demonstrate characteristic patterns of gene expression during breast development. Several of the pathways activated during pubertal development have been implicated in cancer

  12. Feature Selection Methods for Robust Decoding of Finger Movements in a Non-human Primate

    Science.gov (United States)

    Padmanaban, Subash; Baker, Justin; Greger, Bradley

    2018-01-01

    Objective: The performance of machine learning algorithms used for neural decoding of dexterous tasks may be impeded due to problems arising when dealing with high-dimensional data. The objective of feature selection algorithms is to choose a near-optimal subset of features from the original feature space to improve the performance of the decoding algorithm. The aim of our study was to compare the effects of four feature selection techniques, Wilcoxon signed-rank test, Relative Importance, Principal Component Analysis (PCA), and Mutual Information Maximization on SVM classification performance for a dexterous decoding task. Approach: A nonhuman primate (NHP) was trained to perform small coordinated movements—similar to typing. An array of microelectrodes was implanted in the hand area of the motor cortex of the NHP and used to record action potentials (AP) during finger movements. A Support Vector Machine (SVM) was used to classify which finger movement the NHP was making based upon AP firing rates. We used the SVM classification to examine the functional parameters of (i) robustness to simulated failure and (ii) longevity of classification. We also compared the effect of using isolated-neuron and multi-unit firing rates as the feature vector supplied to the SVM. Main results: The average decoding accuracy for multi-unit features and single-unit features using Mutual Information Maximization (MIM) across 47 sessions was 96.74 ± 3.5% and 97.65 ± 3.36% respectively. The reduction in decoding accuracy between using 100% of the features and 10% of features based on MIM was 45.56% (from 93.7 to 51.09%) and 4.75% (from 95.32 to 90.79%) for multi-unit and single-unit features respectively. MIM had best performance compared to other feature selection methods. Significance: These results suggest improved decoding performance can be achieved by using optimally selected features. The results based on clinically relevant performance metrics also suggest that the decoding

  13. High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

    International Nuclear Information System (INIS)

    Yin Jiangmei; Dai Anlan; Laddy, Dominick J.; Yan Jian; Arango, Tatiana; Khan, Amir S.; Lewis, Mark G.; Andersen, Hanne; Kutzler, Michele A.; Draghia-Akli, Ruxandra; Weiner, David B.; Boyer, Jean D.

    2009-01-01

    Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhanced the production of IFN-γ (0.5 mg) and the proliferation of CD4 + and CD8 + T cells, as well as T CM levels in proliferating CD8 + T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-γ and the proliferation of CD4 + and CD8 + T cells and T CM levels in the proliferating CD4 + and CD8 + T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.

  14. Multimodal imaging and in vivo/post mortem co-registration in rodents and non human primates

    International Nuclear Information System (INIS)

    Delzescaux, T.

    2006-01-01

    Within the framework of neuro-degenerative disease studies, animal models still remain essential for the improvement of our understanding of underlying pathological mechanisms and for the discovery and development of potential novel therapeutic approaches. The pre-clinical research especially requires the use of non-human primates models because of the similarities between their brain and Human's, whereas fundamental investigations in many areas of biology and medicine more widely involve the use of rodent models.The recent developments of in vivo imaging systems dedicated to small animals (μ-CT, μ-MRI and μ-PET) have made possible the study of brain anatomic alterations as well as the longitudinal follow-up of metabolism and neurotransmission impairments, which can be involved in neuro-degenerative diseases. In particular, μ-PET is becoming increasingly relevant to assess the efficiency of a potential candidate in the field of drug discovery and development and disease diagnosis. However, until today a few laboratories are equipped with them. Moreover, their limited spatial resolution and the lack of specific biological markers are still major limitations. As a consequence, the scientific community still needs comparative anatomical and/or functional analyses, in particular for studies concerning rodent brain. Hence, post mortem biological imaging remains the powerful, reference and predominantly technology used for small animal imaging and for the validation of in vivo imaging systems. Generally, anatomical and complementary functional information are, respectively, provided by histological staining and autoradiography of corresponding brain sections. The large variety of histological dyes (cresyl violet for Nissl bodies Congo red for amyloid plaques) and radioactive compounds ([ 14 C]Deoxyglucose for cerebral glucose metabolism, [ 14 C]leucine for cerebral protein synthesis [ 14 C]iodoantipyrine for cerebral blood flow), as well as the microscopic range of

  15. A random phased-array for MR-guided transcranial ultrasound neuromodulation in non-human primates.

    Science.gov (United States)

    Chaplin, Vandiver; Phipps, Marshal A; Caskey, Charles F

    2018-04-18

    Transcranial focused ultrasound (FUS) is a non-invasive technique for therapy and study of brain neural activation. Here we report on the design and characterization of a new MR-guided FUS transducer for neuromodulation in non-human primates at 650 kHz. The array is randomized with 128 elements 6.6 mm in diameter, radius of curvature 7.2 cm, opening diameter 10.3 cm (focal ratio 0.7), and 46% coverage. Simulations were used to optimize transducer geometry with respect to focus size, grating lobes, and directivity. Focus size and grating lobes during electronic steering were quantified using hydrophone measurements in water and a three-axis stage. A novel combination of optical tracking and acoustic mapping enabled measurement of the 3D pressure distribution in the cortical region of an ex vivo skull to within ~3.5 mm of the surface, and allowed accurate modelling of the experiment via non-homogeneous 3D acoustic simulations. The data demonstrates acoustic focusing beyond the skull bone, with the focus slightly broadened and shifted proximal to the skull. The fabricated design is capable of targeting regions within the S1 sensorimotor cortex of macaques. © 2018 Institute of Physics and Engineering in Medicine.

  16. The application of sequential sup(99m)Tc-methylene diphosphonate scintigraphy to evaluate bone healing in non human primates

    International Nuclear Information System (INIS)

    Dormehl, I.C.; Mennen, U.; Goosen, D.J.

    1982-01-01

    The study was performed to devise and assess a sensitive non-invasive method for investigated the healing process of long bones in non-human primates. A specific clinical application in mind is the early detection of non-healing or delayed healing of fractures in the aged. Important for accurate evaluation is the consistency of the localisation of the fracture site and the region of healthy bone from each scintiscan for the entire study. The present report concerns a technique which seems to be successful for this purpose, and is found useful towards the clinical application. Four adult chacma baboons (Papio ursinus) were used in the experiment. All four animals were clinically and radiographically normal. They were housed indoors in environmentally controlled rooms for the duration of the experiment and they were fed a balanced commercial diet with water freely available. Eight forearms, i.e. a total of 16 radius and ulna bones were osteotomized with a Gigli saw to create simple standard and controlled fractures

  17. Multimodal imaging and in vivo/post mortem co-registration in rodents and non human primates

    Energy Technology Data Exchange (ETDEWEB)

    Delzescaux, T. [Service Hospitalier Frederic Joliot, Isotopic Imaging, 91 - Orsay (France)

    2006-07-01

    Within the framework of neuro-degenerative disease studies, animal models still remain essential for the improvement of our understanding of underlying pathological mechanisms and for the discovery and development of potential novel therapeutic approaches. The pre-clinical research especially requires the use of non-human primates models because of the similarities between their brain and Human's, whereas fundamental investigations in many areas of biology and medicine more widely involve the use of rodent models.The recent developments of in vivo imaging systems dedicated to small animals ({mu}-CT, {mu}-MRI and {mu}-PET) have made possible the study of brain anatomic alterations as well as the longitudinal follow-up of metabolism and neurotransmission impairments, which can be involved in neuro-degenerative diseases. In particular, {mu}-PET is becoming increasingly relevant to assess the efficiency of a potential candidate in the field of drug discovery and development and disease diagnosis. However, until today a few laboratories are equipped with them. Moreover, their limited spatial resolution and the lack of specific biological markers are still major limitations. As a consequence, the scientific community still needs comparative anatomical and/or functional analyses, in particular for studies concerning rodent brain. Hence, post mortem biological imaging remains the powerful, reference and predominantly technology used for small animal imaging and for the validation of in vivo imaging systems. Generally, anatomical and complementary functional information are, respectively, provided by histological staining and autoradiography of corresponding brain sections. The large variety of histological dyes (cresyl violet for Nissl bodies Congo red for amyloid plaques) and radioactive compounds ([{sup 14}C]Deoxyglucose for cerebral glucose metabolism, [{sup 14}C]leucine for cerebral protein synthesis [{sup 14}C]iodoantipyrine for cerebral blood flow), as well as

  18. The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

    Science.gov (United States)

    Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

    2018-01-15

    Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

  19. A random phased-array for MR-guided transcranial ultrasound neuromodulation in non-human primates

    Science.gov (United States)

    Chaplin, Vandiver; Phipps, Marshal A.; Caskey, Charles F.

    2018-05-01

    Transcranial focused ultrasound (FUS) is a non-invasive technique for therapy and study of brain neural activation. Here we report on the design and characterization of a new MR-guided FUS transducer for neuromodulation in non-human primates at 650 kHz. The array is randomized with 128 elements 6.6 mm in diameter, radius of curvature 7.2 cm, opening diameter 10.3 cm (focal ratio 0.7), and 46% coverage. Simulations were used to optimize transducer geometry with respect to focus size, grating lobes, and directivity. Focus size and grating lobes during electronic steering were quantified using hydrophone measurements in water and a three-axis stage. A novel combination of optical tracking and acoustic mapping enabled measurement of the 3D pressure distribution in the cortical region of an ex vivo skull to within ~3.5 mm of the surface, and allowed accurate modelling of the experiment via non-homogeneous 3D acoustic simulations. The data demonstrates acoustic focusing beyond the skull bone, with the focus slightly broadened and shifted proximal to the skull. The fabricated design is capable of targeting regions within the S1 sensorimotor cortex of macaques.

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

    Science.gov (United States)

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

    2015-10-01

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

  1. Gender markedly modulates behavioral thermoregulation in a non-human primate species, the mouse lemur (Microcebus murinus).

    Science.gov (United States)

    Terrien, J; Perret, M; Aujard, F

    2010-11-02

    Age and gender are known to significantly modulate thermoregulatory capacities in mammals, suggesting strong impacts on behavioral adjustments, which are used to minimize the energy costs of thermoregulation. We tested the effects of sex and age on spontaneous choice of ambient temperature (Ta) in a non-human primate species, the mouse lemur (Microcebus murinus). The animals acclimated to both winter and summer photoperiods, two seasons significantly modifying thermoregulation function, were experimented in a thermal gradient device. During winter, adult males did not show preference for warm Tas whereas old males did. In contrast, female mouse lemurs of both age categories exhibited great preferences for warm Tas. Acclimation to summer revealed that males selected colder Ta for the day than during the night. Such behavior did not exist in females. Old females explored and selected warmer nests than adult ones. This study raised novel issues on the effect of gender on thermoregulatory capacities in the mouse lemur. Females probably use behavioral adjustments to limit energy expenditure and might prefer to preserve energy for maternal investment by anticipation of and during the breeding season. Further experiments focusing on female thermoregulatory capacities are needed to better understand the energy challenge that may occur during winter and summer in female mouse lemurs, and whether this trade-off changes during aging. Copyright © 2010 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-11-30

    Currently, the primary technique employed in circuit-level study of the brain is electrophysiology, recording local field or action potentials (LFPs or APs). However most communication between neurons is chemical and the relationship between electrical activity within neurons and chemical signaling between them is not well understood in vivo, particularly for molecules that signal at least in part by non-synaptic transmission. We describe a multi-contact array and accompanying head stage circuit that together enable concurrent electrophysiological and electrochemical recording. The array is small (electrochemistry) recording. This system is designed for concurrent, dual-mode recording. It is also the only system designed explicitly to meet the challenges of recording in non-human primates. Our system offers the possibility for conducting in vivo studies in a range of species that examine the relationship between the electrical activity of neurons and their chemical environment, with exquisite spatial and temporal precision. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

    Science.gov (United States)

    Dechow, Paul C.; Wang, Qian; Peterson, Jill

    2011-01-01

    Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which

  4. The ten-thousand year fever: rethinking human and wild primate malarias

    National Research Council Canada - National Science Library

    Cormier, Loretta A

    2011-01-01

    .... She also shows how current human-environment interactions, including deforestation and development, create the potential for new forms of malaria to threaten human populations. This book is a model of interdisciplinary integration that will be essential reading in fields from anthropology and biology to public health"--Provided by publisher.

  5. 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

  6. The effects of single dose TBI on hepatic and renal function in non-human primates and patients

    International Nuclear Information System (INIS)

    Broerse, J.J.; Bakker, B.; Davelaar, J.; Leer, J.W.H.; Niemer-Tucker, M.M.B.; Noordijk, E.M.

    1996-01-01

    Total body irradiation (TBI) and bone marrow transplantation (BMT) are common procedures in the treatment of severe combined immune deficiency syndromes, leukemia, non-Hodgkin lymphoma and other hematological disorders. Improved results following TBI and BMT have increased the number of patients in long term follow up. Late detrimental effects of TBI have been investigated in non-human primates and patients with emphasis on vital organs like liver and kidney. The response of monkeys to radiation is not significantly different from that in man. Long term effects of TBI could be studied by keeping 84 monkeys of different ages under continuous observation for a period up to 25 years. Effects on hepatic and renal function were demonstrated using serological and histological parameters. The values of the liver function parameters such as alkaline phosphatase and gamma glutamyl transferase in the irradiated group are significantly increased after TBI. Also the parameters of kidney dysfunction, e.g., Ht and urea show a significant change in the irradiated old aged cohort with respect to the controls. Between 1967 and 1993, 336 bone marrow transplantations were performed at the University Hospital Leiden. The present Study was restricted to those patients who survived at least 18 months after transplantation. This retrospective analysis consequently amounts to 120 patients. The monkey data indicated subclinical organ damage for postirradiation intervals exceeding 15 years. However, up to the present time, the human data do not support these findings since the follow up time is still restricted to a median survival of 4,5 years. Detrimental effects in liver and kidney function at a later stage can not be excluded yet, and careful examinations of the patients remain indicated

  7. Quantitative serology assays for determination of antibody responses to Ebola virus glycoprotein and matrix protein in nonhuman primates and humans.

    Science.gov (United States)

    Vu, Hong; Shulenin, Sergey; Grolla, Allen; Audet, Jonathan; He, Shihua; Kobinger, Gary; Unfer, Robert C; Warfield, Kelly L; Aman, M Javad; Holtsberg, Frederick W

    2016-02-01

    The West Africa Ebola virus disease (EVD) outbreak has reached unprecedented magnitude and caused worldwide concerns for the spread of this deadly virus. Recent findings in nonhuman primates (NHPs) demonstrate that antibodies can be protective against EVD. However, the role of antibody response in vaccine-mediated protection is not fully understood. To address these questions quantitative serology assays are needed for measurement of the antibody response to key Ebola virus (EBOV) proteins. Serology enzyme-linked immunosorbent assays (ELISA's), using a reference detection antibody, were developed in order to standardize the quantitation of antibody levels in vaccinated NHPs or in humans exposed to EBOV or immunized with an EBOV vaccine. Critical reagents were generated to support the development of the serology ELISAs. Recombinant EBOV matrix protein (VP40) was expressed in Escherichia coli and purified. Two variants of the glycoprotein (GP), the ectodomain lacking the transmembrane domain (GPΔTM), and an engineered GP lacking the mucin-like domain (GPΔmuc) were expressed and purified from mammalian cell systems. Using these proteins, three ELISA methods were developed and optimized for reproducibility and robustness, including stability testing of critical reagents. The assay was used to determine the antibody response against VP40, GPΔTM, and GPΔmuc in a NHP vaccine study using EBOV virus-like particles (VLP) vaccine expressing GP, VP40 and the nucleoprotein. Additionally, these ELISAs were used to successfully detect antibody responses to VP40, GPΔTM and GPΔmuc in human sera from EBOV infected individuals. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  9. Non-human primates avoid the detrimental effects of prenatal androgen exposure in mixed-sex litters: combined demographic, behavioral, and genetic analyses.

    Science.gov (United States)

    Bradley, Brenda J; Snowdon, Charles T; McGrew, William C; Lawler, Richard R; Guevara, Elaine E; McIntosh, Annick; O'Connor, Timothy

    2016-12-01

    Producing single versus multiple births has important life history trade-offs, including the potential benefits and risks of sharing a common in utero environment. Sex hormones can diffuse through amniotic fluid and fetal membranes, and females with male littermates risk exposure to high levels of fetal testosterone, which are shown to have masculinizing effects and negative fitness consequences in many mammals. Whereas most primates give birth to single offspring, several New World monkey and strepsirrhine species regularly give birth to small litters. We examined whether neonatal testosterone exposure might be detrimental to females in mixed-sex litters by compiling data from long-term breeding records for seven primate species (Saguinus oedipus; Varecia variegata, Varecia rubra, Microcebus murinis, Mirza coquereli, Cheirogaleus medius, Galago moholi). Litter sex ratios did not differ from the expected 1:2:1 (MM:MF:FF for twins) and 1:2:2:1 (MMM:MMF:MFF:FFF for triplets). Measures of reproductive success, including female survivorship, offspring-survivorship, and inter-birth interval, did not differ between females born in mixed-sex versus all-female litters, indicating that litter-producing non-human primates, unlike humans and rodents, show no signs of detrimental effects from androgen exposure in mixed sex litters. Although we found no evidence for CYP19A1 gene duplications-a hypothesized mechanism for coping with androgen exposure-aromatase protein evolution shows patterns of convergence among litter-producing taxa. That some primates have effectively found a way to circumvent a major cost of multiple births has implications for understanding variation in litter size and life history strategies across mammals. © 2016 Wiley Periodicals, Inc.

  10. Landscape requirements of a primate population in a human-dominated environment

    Directory of Open Access Journals (Sweden)

    Hoffman Tali S

    2012-01-01

    Full Text Available Abstract Introduction As urban and rural land development become widespread features of the global landscape so an understanding of the landscape requirements of displaced and isolated wildlife species becomes increasingly important for conservation planning. In the Cape Peninsula, South Africa, rapid human population growth, and the associated urban and rural land transformation, threatens the sustainability of the local chacma baboon population. Here we analyse spatial data collected from nine of the 12 extant troops to determine their population-level landscape requirements. We use hurdle models to ascertain the key landscape features influencing baboon occurrence and abundance patterns on two hierarchical spatial scales. Results Both spatial scales produced similar results that were ecologically reliable and interpretable. The models indicated that baboons were more likely to occur, and be more abundant, at low altitudes, on steep slopes and in human-modified habitats. The combination of these landscape variables provides baboons with access to the best quality natural and anthropogenic food sources in close proximity to one another and suitable sleeping sites. Surface water did not emerge as an influential landscape feature presumably as the area is not water stressed. Conclusions The model results indicate that land development in the Cape Peninsula has pushed baboons into increasingly marginal natural habitat while simultaneously providing them with predictable and easily accessible food sources in human-modified habitats. The resultant spatial competition between humans and baboons explains the high levels of human-baboon conflict and further erosion of the remaining land fragments is predicted to exacerbate competition. This study demonstrates how the quantification of animal landscape requirements can provide a mechanism for identifying priority conservation areas at the human-wildlife interface.

  11. PrimateLit Database

    Science.gov (United States)

    Primate Info Net Related Databases NCRR PrimateLit: A bibliographic database for primatology Top of any problems with this service. We welcome your feedback. The PrimateLit database is no longer being Resources, National Institutes of Health. The database is a collaborative project of the Wisconsin Primate

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

    Directory of Open Access Journals (Sweden)

    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. Monomorphism in humans and sequence differences among higher primates for a sequence tagged site (STS) in homeo box cluster 2 as assayed by denaturing gradient electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Ruano, G.; Ruddle, F.H.; Kidd, K.K. (Yale Univ., New Haven, CT (United States)); Gray, M.R. (Tufts Univ., Boston, MA (United States)); Miki, Tetsuro (Osaka Univ. (Japan)); Ferguson-Smith, A.C. (Inst. of Animal Physiology and Genetics Research, Cambridge (United Kingdom))

    1990-03-11

    The human homeo box cluster 2 (HOX2) contains genes coding for DNA binding proteins involved in developmental control and is highly conserved between mouse and man. The authors have applied in concert the Polymerase Chain Reaction (PCR) and Denaturing Gradient Electrophoresis (DGE) to amplify defined primate HOX2 segments and to detect sequence differences among them. They have sequenced a PstI fragment 4 kb upstream from HOX 2.2 and synthesized primers delimiting both halves of 630 bp segment within it PCR on various unrelated humans and SC-PCR on chimpanzee, gorilla, orangutan and gibbon yielded products of the same length for each primer pair.

  14. Perceptual elements in brain mechanisms of acoustic communication in humans and nonhuman primates.

    Science.gov (United States)

    Reser, David H; Rosa, Marcello

    2014-12-01

    Ackermann et al. outline a model for elaboration of subcortical motor outputs as a driving force for the development of the apparently unique behaviour of language in humans. They emphasize circuits in the striatum and midbrain, and acknowledge, but do not explore, the importance of the auditory perceptual pathway for evolution of verbal communication. We suggest that understanding the evolution of language will also require understanding of vocalization perception, especially in the auditory cortex.

  15. First comparative approach to touchscreen-based visual object-location paired-associates learning in humans (Homo sapiens) and a nonhuman primate (Microcebus murinus).

    Science.gov (United States)

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

    2018-05-10

    A recent study suggests that a specific, touchscreen-based task on visual object-location paired-associates learning (PAL), the so-called Different PAL (dPAL) task, allows effective translation from animal models to humans. Here, we adapted the task to a nonhuman primate (NHP), the gray mouse lemur, and provide first evidence for the successful comparative application of the task to humans and NHPs. Young human adults reach the learning criterion after considerably less sessions (one order of magnitude) than young, adult NHPs, which is likely due to faster and voluntary rejection of ineffective learning strategies in humans and almost immediate rule generalization. At criterion, however, all human subjects solved the task by either applying a visuospatial rule or, more rarely, by memorizing all possible stimulus combinations and responding correctly based on global visual information. An error-profile analysis in humans and NHPs suggests that successful learning in NHPs is comparably based either on the formation of visuospatial associative links or on more reflexive, visually guided stimulus-response learning. The classification in the NHPs is further supported by an analysis of the individual response latencies, which are considerably higher in NHPs classified as spatial learners. Our results, therefore, support the high translational potential of the standardized, touchscreen-based dPAL task by providing first empirical and comparable evidence for two different cognitive processes underlying dPAL performance in primates. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  16. Prevalence of antibody to adult T-cell leukemia virus-associated antigens (ATLA) in Japanese monkeys and other non-human primates.

    Science.gov (United States)

    Hayami, M; Komuro, A; Nozawa, K; Shotake, T; Ishikawa, K; Yamamoto, K; Ishida, T; Honjo, S; Hinuma, Y

    1984-02-15

    The prevalence of adult T-cell-leukemia virus (ATLV) infection was examined in Japanese monkeys living naturally in various parts of Japan and in other species of non-human primates imported into and kept in Japan. Sera of 2,650 Japanese monkeys from 41 troops throughout Japan were tested. High incidences of anti-ATLV-associated antigen (ATLA)-positive monkeys were found in most troops, not only in the endemic area of human ATL(Southwestern Japan), but also in non-endemic areas. The incidence of sero-positive individuals increased gradually with age, reaching a maximum when the animals became adult, indicating age dependency, like that found by epidemiological studies on humans. Anti-ATLA antibodies were also detected in 90 of 815 sera of imported non-human primates of 33 species other than Japanese monkeys. All the anti-ATLA sero-positive monkeys were Catarrhines (Old World monkeys), mainly macaques of Asian origin. Some sero-positive monkeys were also found among animals of African origin, but no antibody was detected in Prosimians and Platyrrhines (New World monkeys). The clear-cut difference between the geographical distribution of sero-positive simians and that of humans indicates the improbability of direct transmission of ATLV from simians to humans.

  17. Chronic bronchiolitis in non-human primates after prolonged ozone exposure

    International Nuclear Information System (INIS)

    Eustis, S.L.

    1979-01-01

    Bonnet monkeys (Macaca radiata) were exposed to 0.0, 0.5, and 0.8 ppM ozone for 7, 28, or 90 consecutive d, eight h per d. Changes in the lung evoked by prolonged oxidant exposure were evaluated by light microscopy, scanning electron microscopy, transmission electron microscopy, autoradiography, and morphometry. Morphological changes were principally characterized as a low-grade chronic respiratory bronchiolitis. Proximal generations of respiratory bronchioles were the most consistently affected region of the pulmonary acinus. Major features of the bronchiolitis were intraluminal accumulations of macrophages and hypertrophy and hyperplasia of cuboidal bronchiolar epithelial cells. The degree of inflammation was greatest at the 0.8 ppM ozone concentration at each exposure period. The number of inflammatory cells observed at 90 d, however, was about one-half that observed at 7 d. Tritiated thymidine labeling and differential cell counts of respiratory bronchiolar epithelium demonstrated a proliferative response and an increase in the proportion of cubiodal bronchiolar cells which presumably function as the progenitor cell during cell renewal and repair of the epithelium. The labeling index remained elevated above control values through 90 d of ozone exposure despite a reduction below 7 d values at both 28 and 90 d. The epithelial hyperplasia persisted through 90 d at a level similar to but slightly above that present at 7 d. Since cell differentials remained shifted at 28 and 90 d, it appears that persistent ozone exposure delayed maturation and transformation of cubiodal bronchiolar cells to their mature phenotype

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

    Science.gov (United States)

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

    2016-01-01

    Objective Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10–30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30–60 s, but there was no correlation with beta band power. Significance This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology. PMID:26469737

  19. Functional consequences of cocaine expectation: findings in a non-human primate model of cocaine self-administration.

    Science.gov (United States)

    Porrino, Linda J; Beveridge, Thomas J R; Smith, Hilary R; Nader, Michael A

    2016-05-01

    Exposure to stimuli and environments associated with drug use is considered one of the most important contributors to relapse among substance abusers. Neuroimaging studies have identified neural circuits underlying these responses in cocaine-dependent subjects. But these studies are often difficult to interpret because of the heterogeneity of the participants, substances abused, and differences in drug histories and social variables. Therefore, the goal of this study was to assess the functional effects of exposure to cocaine-associated stimuli in a non-human primate model of cocaine self-administration, providing precise control over these variables, with the 2-[(14) C]deoxyglucose method. Rhesus monkeys self-administered 0.3 mg/kg/injection cocaine (n = 4) under a fixed-interval 3-minute (FI 3-min) schedule of reinforcement (30 injections/session) for 100 sessions. Control animals (n = 4) underwent identical schedules of food reinforcement. Sessions were then discontinued for 30 days, after which time, monkeys were exposed to cocaine- or food-paired cues, and the 2-[(14) C]deoxyglucose experiment was conducted. The presentation of the cocaine-paired cues resulted in significant increases in functional activity within highly restricted circuits that included portions of the pre-commissural striatum, medial prefrontal cortex, rostral temporal cortex and limbic thalamus when compared with control animals presented with the food-paired cues. The presentation of cocaine-associated cues increased brain functional activity in contrast to the decreases observed after cocaine consumption. Furthermore, the topography of brain circuits engaged by the expectation of cocaine is similar to the distribution of effects during the earliest phases of cocaine self-administration, prior to the onset of neuroadaptations that accompany chronic cocaine exposure. © 2015 Society for the Study of Addiction.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2012-11-01

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

  4. Role of Kisspeptin and Neurokinin B in Puberty in Female Non-Human Primates

    OpenAIRE

    Ei Terasawa; Ei Terasawa; James P. Garcia; Stephanie B. Seminara; Kim L. Keen

    2018-01-01

    In human patients, loss-of-function mutations in the genes encoding kisspeptin (KISS1) and neurokinin B (NKB) and their receptors (KISS1R and NK3R, respectively) result in an abnormal timing of puberty or the absence of puberty. To understand the neuroendocrine mechanism of puberty, we investigated the contribution of kisspeptin and NKB signaling to the pubertal increase in GnRH release using rhesus monkeys as a model. Direct measurements of GnRH and kisspeptin in the median eminence of the h...

  5. Myofibroblast Numbers are Elevated in Human Elbow Capsules After Trauma

    OpenAIRE

    Hildebrand, Kevin A.; Zhang, Mei; van Snellenberg, Wistara; King, Graham J. W.; Hart, David A.

    2004-01-01

    Elbow contractures, a frequent problem after injury, can be treated by excision of the joint capsule. However, the underlying changes in the joint capsule are poorly understood. Based on skin healing work, we examined the hypotheses that myofibroblast numbers and expression of a myofibroblast marker α-smooth muscle actin, are elevated in patients with posttraumatic joint contractures. Anterior capsules were obtained from six patients who had operative release of posttraumatic contractures gre...

  6. Omega-3 PUFA supplementation differentially affects behavior and cognition in the young and aged non-human primate Grey mouse lemur (Microcebus murinus

    Directory of Open Access Journals (Sweden)

    Pifferi Fabien

    2014-01-01

    Full Text Available Data are divergent about the ability of dietary ω3 fatty acids to prevent age-associated cognitive decline. Most of the clinical trials failed to demonstrate a protective effect of ω3 fatty acids against cognitive decline and methodological issues are still under debate. Conversely to human studies, experiments performed in adult rodents clearly indicate that long chain ω3 fatty acids play a beneficial role in behavioral and cognitive functions. Inconsistent observations between human and rodent studies highlight the importance of the use of non-human primate models. We recently started a series of experiments on Grey mouse lemurs, an emerging non-human primate model of aging in order to assess the impact of ω3 fatty acids dietary supplementation on several brain functions. These experiments started with the determination of the fatty acids composition of target organs (brain, adipose tissue, liver, plasma of animals fed under control diet. We then explored the impact of ω3 polyunsaturated fatty acids (PUFA supplementation on cognition and behavior in young and aged grey mouse lemurs. The aim of the present review is to compare the observations made in young and aged grey mouse lemurs and to explore the possibilities of new experiments in order to bridge the gap between rodents and Humans.

  7. Black and gold howler monkeys (Alouatta caraya) as sentinels of ecosystem health: patterns of zoonotic protozoa infection relative to degree of human-primate contact.

    Science.gov (United States)

    Kowalewski, Martin M; Salzer, Johanna S; Deutsch, Joseph C; Raño, Mariana; Kuhlenschmidt, Mark S; Gillespie, Thomas R

    2011-01-01

    Exponential expansion of human populations and human activities within primate habitats has resulted in high potential for pathogen exchange creating challenges for biodiversity conservation and global health. Under such conditions, resilient habitat generalists such as black and gold howler monkeys (Alouatta caraya) may act as effective sentinels to overall ecosystem health and alert us to impending epidemics in the human population. To better understand this potential, we examined noninvasively collected fecal samples from black and gold howler monkeys from remote, rural, and village populations in Northern Argentina. We examined all samples (n=90) for the zoonotic protozoa Cryptosporidium sp. and Giardia sp. via immunofluorescent antibody (IFA) detection. All samples were negative for Cryptosporidium sp. The prevalence of Giardia sp. was significantly higher at the rural site (67%) compared with the remote forest (57%) and village (40%) sites. A lack of Cryptosporidium sp. in all samples examined suggests that this pathogen is not a natural component of the howler parasite communities at these sites and that current land-use patterns and livestock contact are not exposing Argentine howler monkeys to this pathogen. High prevalence of Giardia sp. at all sites suggests that howler monkeys may serve as a viable reservoir for Giardia. Significantly higher prevalence of Giardia sp. at the rural site, where primate-livestock contact is highest, suggests the presence of multiple Giardia clades or increased exposure to Giardia through repeated zoonotic transmission among nonhuman primates, livestock, and/or people. These results highlight the need for future research into the epidemiology, cross-species transmission ecology, and clinical consequences of Giardia and other infectious agents not only in humans and livestock, but also in the wild animals that share their environments. © 2010 Wiley-Liss, Inc.

  8. The Cellular Composition and Glia-Neuron Ratio in the Spinal Cord of a Human and a Nonhuman Primate: Comparison With Other Species and Brain Regions.

    Science.gov (United States)

    Bahney, Jami; von Bartheld, Christopher S

    2018-04-01

    The cellular composition of brains shows largely conserved, gradual evolutionary trends between species. In the primate spinal cord, however, the glia-neuron ratio was reported to be greatly increased over that in the rodent spinal cord. Here, we re-examined the cellular composition of the spinal cord of one human and one nonhuman primate species by employing two different counting methods, the isotropic fractionator and stereology. We also determined whether segmental differences in cellular composition, possibly reflecting increased fine motor control of the upper extremities, may explain a sharply increased glia-neuron ratio in primates. In the cynomolgus monkey spinal cord, the isotropic fractionator and stereology yielded 206-275 million cells, of which 13.3-25.1% were neurons (28-69 million). Stereological estimates yielded 21.1% endothelial cells and 65.5% glial cells (glia-neuron ratio of 4.9-5.6). In human spinal cords, the isotropic fractionator and stereology generated estimates of 1.5-1.7 billion cells and 197-222 million neurons (13.4% neurons, 12.2% endothelial cells, 74.8% glial cells), and a glia-neuron ratio of 5.6-7.1, with estimates of neuron numbers in the human spinal cord based on morphological criteria. The non-neuronal to neuron ratios in human and cynomolgus monkey spinal cords were 6.5 and 3.2, respectively, suggesting that previous reports overestimated this ratio. We did not find significant segmental differences in the cellular composition between cervical, thoracic and lumbar levels. When compared with brain regions, the spinal cord showed gradual increases of the glia-neuron ratio with increasing brain mass, similar to the cerebral cortex and the brainstem. Anat Rec, 301:697-710, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Antibody Prophylaxis Against Dengue Virus 2 Infection in Non-Human Primates.

    Science.gov (United States)

    Simmons, Monika; Putnak, Robert; Sun, Peifang; Burgess, Timothy; Marasco, Wayne A

    2016-11-02

    Passive immunization with anti-dengue virus (DENV) immune serum globulin (ISG) or monoclonal antibodies (Mabs) may serve to supplement or replace vaccination for short-term dengue immune prophylaxis. In the present study, we sought to establish proof-of-concept by evaluating several DENV-neutralizing antibodies for their ability to protect rhesus macaques against viremia following live virus challenge, including human anti-dengue ISG, and a human Mab (Mab11/wt) and its genetically engineered variant (Mab11/mutFc) that is unable to bind to cells with Fc gamma receptors (FcγR) and potentiate antibody-dependent enhancement (ADE). In the first experiment, groups of animals received ISG or Mab11/wt at low doses (3-10 mg/kg) or a saline control followed by challenge with DENV-2 at day 10 or 30. After passive immunization, only low-titered circulating virus-neutralizing antibody titers were measured in both groups, which were undetectable by day 30. After challenge at day 10, a reduction in viremia duration compared with the control was seen only in the ISG group (75%). However, after a day 30 challenge, no reduction in viremia was observed in both immunized groups. In a second experiment to test the effect of higher antibody doses on short-term protection, groups received either ISG, Mab11/wt, Mab11/mutFc (each at 25 mg/kg) or saline followed by challenge with DENV-2 on day 10. Increased virus-neutralizing antibody titers were detected in all groups at day 5 postinjection, with geometric mean titers (GMTs) of 464 (ISG), 313 (Mab11/wt), and 309 (Mab11/mutFc). After challenge, there was complete protection against viremia in the group that received ISG, and a reduction in viremia duration of 89% and 83% in groups that received Mab11/wt and Mab11/mutFc, respectively. An in vitro ADE assay in Fcγ receptor-bearing K562 cells with sera collected immediately before challenge showed increased DENV-2 infection levels in the presence of both ISG and Mab11/wt, which peaked at a

  10. Role of Kisspeptin and Neurokinin B in Puberty in Female Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Ei Terasawa

    2018-04-01

    Full Text Available In human patients, loss-of-function mutations in the genes encoding kisspeptin (KISS1 and neurokinin B (NKB and their receptors (KISS1R and NK3R, respectively result in an abnormal timing of puberty or the absence of puberty. To understand the neuroendocrine mechanism of puberty, we investigated the contribution of kisspeptin and NKB signaling to the pubertal increase in GnRH release using rhesus monkeys as a model. Direct measurements of GnRH and kisspeptin in the median eminence of the hypothalamus with infusion of agonists and antagonists for kisspeptin and NKB reveal that kisspeptin and NKB signaling stimulate GnRH release independently or collaboratively by forming kisspeptin and NKB neuronal networks depending on the developmental age. For example, while in prepubertal females, kisspeptin and NKB signaling independently stimulate GnRH release, in pubertal females, the formation of a collaborative kisspeptin and NKB network further accelerates the pubertal increase in GnRH release. It is speculated that the collaborative mechanism between kisspeptin and NKB signaling to GnRH neurons is necessary for the complex reproductive function in females.

  11. Costimulation blockade and regulatory T-cells in a non-human primate model of kidney allograft transplantation

    NARCIS (Netherlands)

    Haanstra, Krista Geraldine

    2008-01-01

    Successful tolerance induction therapies in rodents are for the most part unsuccessful in larger primates. Costimulation blockade by anti-CD40 or anti-CD40 + anti-CD86 in the life-supporting kidney allograft model in the rhesus monkey prevented graft rejection during treatment but did not induce

  12. Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates

    Science.gov (United States)

    Andrews, Rachel N.; Metheny-Barlow, Linda J.; Peiffer, Ann M.; Hanbury, David B.; Tooze, Janet A.; Bourland, J. Daniel; Hampson, Robert E.; Deadwyler, Samuel A.; Cline, J. Mark

    2017-01-01

    Andrews, R. N., Metheny-Barlow, L. J., Peiffer, A. M., Hanbury, D. B., Tooze, J. A., Bourland, J. D., Hampson, R. E., Deadwyler, S. A. and Cline, J. M. Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates. Radiat. Res. 187, 599–611 (2017). Fractionated whole-brain irradiation (fWBI) is a mainstay of treatment for patients with intracranial neoplasia; however late-delayed radiation-induced normal tissue injury remains a major adverse consequence of treatment, with deleterious effects on quality of life for affected patients. We hypothesize that cerebrovascular injury and remodeling after fWBI results in ischemic injury to dependent white matter, which contributes to the observed cognitive dysfunction. To evaluate molecular effectors of radiation-induced brain injury (RIBI), real-time quantitative polymerase chain reaction (RT-qPCR) was performed on the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46), hippocampus and temporal white matter of 4 male Rhesus macaques (age 6–11 years), which had received 40 Gray (Gy) fWBI (8 fractions of 5 Gy each, twice per week), and 3 control comparators. All fWBI animals developed neurologic impairment; humane euthanasia was elected at a median of 6 months. Radiation-induced brain injury was confirmed histopathologically in all animals, characterized by white matter degeneration and necrosis, and multifocal cerebrovascular injury consisting of perivascular edema, abnormal angiogenesis and perivascular extracellular matrix deposition. Herein we demonstrate that RIBI is associated with white matter-specific up-regulation of hypoxia-associated lactate dehydrogenase A (LDHA) and that increased gene expression of fibronectin 1 (FN1), SERPINE1 and matrix metalloprotease 2 (MMP2) may contribute to cerebrovascular remodeling in late-delayed RIBI. Additionally, vascular stability and maturation associated tumor necrosis super family member 15 (TNFSF15) and

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2010-05-29

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

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

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    Daniella S. Battagello

    2017-07-01

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

  16. HERV-W group evolutionary history in non-human primates: characterization of ERV-W orthologs in Catarrhini and related ERV groups in Platyrrhini.

    Science.gov (United States)

    Grandi, Nicole; Cadeddu, Marta; Blomberg, Jonas; Mayer, Jens; Tramontano, Enzo

    2018-01-19

    The genomes of all vertebrates harbor remnants of ancient retroviral infections, having affected the germ line cells during the last 100 million years. These sequences, named Endogenous Retroviruses (ERVs), have been transmitted to the offspring in a Mendelian way, being relatively stable components of the host genome even long after their exogenous counterparts went extinct. Among human ERVs (HERVs), the HERV-W group is of particular interest for our physiology and pathology. A HERV-W provirus in locus 7q21.2 has been coopted during evolution to exert an essential role in placenta, and the group expression has been tentatively linked to Multiple Sclerosis and other diseases. Following up on a detailed analysis of 213 HERV-W insertions in the human genome, we now investigated the ERV-W group genomic spread within primate lineages. We analyzed HERV-W orthologous loci in the genome sequences of 12 non-human primate species belonging to Simiiformes (parvorders Catarrhini and Platyrrhini), Tarsiiformes and to the most primitive Prosimians. Analysis of HERV-W orthologous loci in non-human Catarrhini primates revealed species-specific insertions in the genomes of Chimpanzee (3), Gorilla (4), Orangutan (6), Gibbon (2) and especially Rhesus Macaque (66). Such sequences were acquired in a retroviral fashion and, in the majority of cases, by L1-mediated formation of processed pseudogenes. There were also a number of LTR-LTR homologous recombination events that occurred subsequent to separation of Catarrhini sub-lineages. Moreover, we retrieved 130 sequences in Marmoset and Squirrel Monkeys (family Cebidae, Platyrrhini parvorder), identified as ERV1-1_CJa based on RepBase annotations, which appear closely related to the ERV-W group. Such sequences were also identified in Atelidae and Pitheciidae, representative of the other Platyrrhini families. In contrast, no ERV-W-related sequences were found in genome sequence assemblies of Tarsiiformes and Prosimians. Overall, our

  17. Transmission of MDR MRSA between primates, their environment and personnel at a United States primate centre.

    Science.gov (United States)

    Soge, Olusegun O; No, David; Michael, Karen E; Dankoff, Jennifer; Lane, Jennifer; Vogel, Keith; Smedley, Jeremy; Roberts, Marilyn C

    2016-10-01

    MDR MRSA isolates cultured from primates, their facility and primate personnel from the Washington National Primate Research Center were characterized to determine whether they were epidemiologically related to each other and if they represented common local human-associated MRSA strains. Human and primate nasal and composite environmental samples were collected, enriched and selected on medium supplemented with oxacillin and polymyxin B. Isolates were biochemically verified as Staphylococcus aureus and screened for the mecA gene. Selected isolates were characterized using SCCmec typing, MLST and WGS. Nasal cultures were performed on 596 primates and 105 (17.6%) were MRSA positive. Two of 79 (2.5%) personnel and two of 56 (3.6%) composite primate environmental facility samples were MRSA positive. Three MRSA isolates from primates, one MRSA from personnel, two environmental MRSA and one primate MSSA were ST188 and were the same strain type by conventional typing methods. ST188 isolates were related to a 2007 ST188 human isolate from Hong Kong. Both MRSA isolates from out-of-state primates had a novel MLST type, ST3268, and an unrelated group. All isolates carried ≥1 other antibiotic resistance gene(s), including tet(38), the only tet gene identified. ST188 is very rare in North America and has almost exclusively been identified in people from Pan-Asia, while ST3268 is a newly reported MRSA type. The data suggest that the primate MDR MRSA was unlikely to come from primate centre employees. Captive primates are likely to be an unappreciated source of MRSA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Delayed revascularization of islets after transplantation by IL-6 blockade in pig to non-human primate islet xenotransplantation model.

    Science.gov (United States)

    Min, Byoung-Hoon; Shin, Jun-Seop; Kim, Jong-Min; Kang, Seong-Jun; Kim, Hyun-Je; Yoon, Il-Hee; Park, Su-Kyoung; Choi, Ji-Won; Lee, Min-Suk; Park, Chung-Gyu

    2018-01-01

    Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model. Also, the endothelial cell origin in a new vessel of the transplanted pig islets was determined. Pig islets were isolated from designated pathogen-free (DPF) SNU miniature pigs and transplanted via portal vein into five streptozotocin-induced diabetic monkeys. One group (n = 2, basal group) was treated with anti-thymoglobulin (ATG), anti-CD40 antibody (2C10R4), sirolimus, and tacrolimus, and the other group was additionally given tocilizumab on top of basal immunosuppression (n = 3, Tocilizumab group). To confirm IL-6 blocking effect, C-reactive protein (CRP) levels and serum IL-6 concentration were measured. Scheduled biopsy of the margin of the posterior segment right lobe inferior of the liver was performed at 3 weeks after transplantation to assess the degree of revascularization of the transplanted islets. Immunohistochemical staining using anti-insulin, anti-CD31 antibodies, and lectin IB4 was conducted to find the origin of endothelial cells in the islet graft. CRP significantly increased at 1~2 days after transplantation in Basal group, but not in Tocilizumab group, and higher serum IL-6 concentration was measured in latter group, showing the biological potency of tocilizumab. In Basal group, well-developed endothelial cells were observed on the peri- and intraislet area, whereas the number of CD31 + cells in the intraislet space was significantly reduced in Tocilizumab group. Finally, new endothelial

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

    Sosa, Sebastian; Zhang, Peng; Cabanes, Guénaël

    2017-06-01

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

  1. The visual development of hand-centered receptive fields in a neural network model of the primate visual system trained with experimentally recorded human gaze changes.

    Science.gov (United States)

    Galeazzi, Juan M; Navajas, Joaquín; Mender, Bedeho M W; Quian Quiroga, Rodrigo; Minini, Loredana; Stringer, Simon M

    2016-01-01

    Neurons have been found in the primate brain that respond to objects in specific locations in hand-centered coordinates. A key theoretical challenge is to explain how such hand-centered neuronal responses may develop through visual experience. In this paper we show how hand-centered visual receptive fields can develop using an artificial neural network model, VisNet, of the primate visual system when driven by gaze changes recorded from human test subjects as they completed a jigsaw. A camera mounted on the head captured images of the hand and jigsaw, while eye movements were recorded using an eye-tracking device. This combination of data allowed us to reconstruct the retinal images seen as humans undertook the jigsaw task. These retinal images were then fed into the neural network model during self-organization of its synaptic connectivity using a biologically plausible trace learning rule. A trace learning mechanism encourages neurons in the model to learn to respond to input images that tend to occur in close temporal proximity. In the data recorded from human subjects, we found that the participant's gaze often shifted through a sequence of locations around a fixed spatial configuration of the hand and one of the jigsaw pieces. In this case, trace learning should bind these retinal images together onto the same subset of output neurons. The simulation results consequently confirmed that some cells learned to respond selectively to the hand and a jigsaw piece in a fixed spatial configuration across different retinal views.

  2. The Effect of Varying Jaw-elevator Muscle Forces on a Finite Element Model of a Human Cranium.

    Science.gov (United States)

    Toro-Ibacache, Viviana; O'Higgins, Paul

    2016-07-01

    Finite element analyses simulating masticatory system loading are increasingly undertaken in primates, hominin fossils and modern humans. Simplifications of models and loadcases are often required given the limits of data and technology. One such area of uncertainty concerns the forces applied to cranial models and their sensitivity to variations in these forces. We assessed the effect of varying force magnitudes among jaw-elevator muscles applied to a finite element model of a human cranium. The model was loaded to simulate incisor and molar bites using different combinations of muscle forces. Symmetric, asymmetric, homogeneous, and heterogeneous muscle activations were simulated by scaling maximal forces. The effects were compared with respect to strain distribution (i.e., modes of deformation) and magnitudes; bite forces and temporomandibular joint (TMJ) reaction forces. Predicted modes of deformation, strain magnitudes and bite forces were directly proportional to total applied muscle force and relatively insensitive to the degree of heterogeneity of muscle activation. However, TMJ reaction forces and mandibular fossa strains decrease and increase on the balancing and working sides according to the degree of asymmetry of loading. These results indicate that when modes, rather than magnitudes, of facial deformation are of interest, errors in applied muscle forces have limited effects. However the degree of asymmetric loading does impact on TMJ reaction forces and mandibular fossa strains. These findings are of particular interest in relation to studies of skeletal and fossil material, where muscle data are not available and estimation of muscle forces from skeletal proxies is prone to error. Anat Rec, 299:828-839, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Pathogenesis of varicelloviruses in primates.

    Science.gov (United States)

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

    2015-01-01

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

  4. Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.

    Science.gov (United States)

    Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W; Thiebaut, Rodolphe; Cope, Alethea; Scarlatti, Gabriella; Shattock, Robin J

    2016-06-01

    Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have

  5. Brains, Genes and Primates

    Science.gov (United States)

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  6. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior

    Science.gov (United States)

    Curtis, Britni; Liberato, Noelle; Rulien, Megan; Morrisroe, Kelly; Kenney, Caroline; Yutuc, Vernon; Ferrier, Clayton; Marti, C. Nathan; Mandell, Dorothy; Burbacher, Thomas M.; Sackett, Gene P.

    2015-01-01

    Background In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. Objectives The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. Methods We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate. Results We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. Conclusions This comprehensive 5-year case–control study, which closely examined

  7. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson’s disease

    Science.gov (United States)

    Crum, William R.; Gerwig, Madeline; Vernon, Anthony C.; Patel, Priya; Jackson, Michael J.; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud M.

    2017-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics. PMID:28738061

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

    Directory of Open Access Journals (Sweden)

    Stephanie D Byrum

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

  9. Elevated mercury concentrations in humans of Madre de Dios, Peru.

    Directory of Open Access Journals (Sweden)

    Katy Ashe

    Full Text Available The enormous increase in practically unregulated mining in Madre de Dios Peru is leading to massive release of liquid elemental mercury to the environment. Rapidly increasing global prices for gold are causing a massive upsurge in artisanal mining in the Peruvian Amazon, considered to be one of the most biodiverse places on the planet. This study identifies the current levels of mercury in the human population, through identifying levels of total mercury in human hair in mining zones of Madre de Dios Department and in the nearby city of Puerto Maldonado. A regression analysis reveals that fish consumption, gender, and location of residence were significant indicators of mercury levels; while duration of residence and age had no significant relationship to mercury levels. Increased fish consumption levels were the strongest indicators of increased total mercury levels across the entire population. The levels of total mercury in hair was significantly (α = 0.05 higher in mining zones, than Puerto Maldonado. In both areas men had significantly higher levels than women, likely due to a difference in metabolism or varying levels of direct involvement in gold mining- a male predominated industry. This is the first study to show the health threat that mercury poses to this region, however further research needs to be done to gain a more refined understanding of the predominant routes of exposure in this population.

  10. Elevated mercury concentrations in humans of Madre de Dios, Peru.

    Science.gov (United States)

    Ashe, Katy

    2012-01-01

    The enormous increase in practically unregulated mining in Madre de Dios Peru is leading to massive release of liquid elemental mercury to the environment. Rapidly increasing global prices for gold are causing a massive upsurge in artisanal mining in the Peruvian Amazon, considered to be one of the most biodiverse places on the planet. This study identifies the current levels of mercury in the human population, through identifying levels of total mercury in human hair in mining zones of Madre de Dios Department and in the nearby city of Puerto Maldonado. A regression analysis reveals that fish consumption, gender, and location of residence were significant indicators of mercury levels; while duration of residence and age had no significant relationship to mercury levels. Increased fish consumption levels were the strongest indicators of increased total mercury levels across the entire population. The levels of total mercury in hair was significantly (α = 0.05) higher in mining zones, than Puerto Maldonado. In both areas men had significantly higher levels than women, likely due to a difference in metabolism or varying levels of direct involvement in gold mining- a male predominated industry. This is the first study to show the health threat that mercury poses to this region, however further research needs to be done to gain a more refined understanding of the predominant routes of exposure in this population.

  11. Termini of human chromosomes display elevated rates of mitotic recombination.

    Science.gov (United States)

    Cornforth, M N; Eberle, R L

    2001-01-01

    The strand-specific in situ hybridization technique of CO-FISH was used to probe telomeres of human mitotic cells in order to determine the spontaneous frequency of crossover. This approach allowed the detection of recombinational crossovers occurring anywhere along the length of individual chromosomes, including reciprocal events taking place between sister chromatids. Although the process of sister chromatid exchange (SCE) is the most prominent type of recombination in somatic mammalian cells, our results show that SCEs accounted for less than a third of the recombinational events revealed by CO-FISH. It is concluded that chromosomal regions near the termini of chromosome arms undergo extraordinarily high rates of spontaneous recombination, producing terminal crossovers whose small size precludes detection by standard cytogenetic methods. That similar results were observed for transformed epithelial cells, as well as primary fibroblasts, suggests that the phenomenon is a common characteristic of human cells. These findings are noteworthy because, although telomeric and subtelomeric DNA is known to be preferentially involved in certain types of recombination, the tips of somatic mammalian chromosomes have not previously been identified as preferred sites for crossover. Implications of these results are discussed in terms of limitations imposed on CO-FISH for its proposed use in directional hybridization mapping.

  12. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    International Nuclear Information System (INIS)

    Ejima, Yosuke

    1988-01-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G 0 or G 1 phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases. (author)

  13. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Ejima, Yosuke; Ikushima, Takaji (ed.)

    1988-07-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G/sub 0/ or G/sub 1/ phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases.

  14. 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

  15. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  17. 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.

  18. Elevated Serum Level of Human Alkaline Phosphatase in Obesity

    International Nuclear Information System (INIS)

    Khan, A. R.; Awan, F. R.; Najam, S. S.; Islam, M.; Siddique, T.; Zain, M.

    2015-01-01

    Objective: To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. Methods: The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass index: normal weight (<25kg/m2), overweight (25-27kg/m2) and obese (>27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. Results: Of the 197 subjects, 97(49 percent) were obese and 100(51 percent) were non-obese. The serum alkaline phosphatase level increased in obese (214±6.4 IU/L) compared to the non-obese subjects (184.5±5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. Conclusion: Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity. (author)

  19. Cooperation and deception in primates.

    Science.gov (United States)

    Hall, Katie; Brosnan, Sarah F

    2017-08-01

    Though competition and cooperation are often considered opposing forces in an arms race driving natural selection, many animals, including humans, cooperate in order to mitigate competition with others. Understanding others' psychological states, such as seeing and knowing, others' goals and intentions, and coordinating actions are all important for complex cooperation-as well as for predicting behavior in order to take advantage of others through tactical deception, a form of competition. We outline evidence of primates' understanding of how others perceive the world, and then consider how the evidence from both deception and cooperation fits this framework to give us a more complete understanding of the evolution of complex social cognition in primates. In experimental food competitions, primates flexibly manipulate group-mates' behavior to tactically deceive them. Deception can infiltrate cooperative interactions, such as when one takes an unfair share of meat after a coordinated hunt. In order to counter competition of this sort, primates maintain cooperation through partner choice, partner control, and third party punishment. Yet humans appear to stand alone in their ability to understand others' beliefs, which allows us not only to deceive others with the explicit intent to create a false belief, but it also allows us to put ourselves in others' shoes to determine when cheaters need to be punished, even if we are not directly disadvantaged by the cheater. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Vector movement underlies avian malaria at upper elevation in Hawaii: implications for transmission of human malaria.

    Science.gov (United States)

    Freed, Leonard A; Cann, Rebecca L

    2013-11-01

    With climate warming, malaria in humans and birds at upper elevations is an emerging infectious disease because development of the parasite in the mosquito vector and vector life history are both temperature dependent. An enhanced-mosquito-movement model from climate warming predicts increased transmission of malaria at upper elevation sites that are too cool for parasite development in the mosquito vector. We evaluate this model with avian malaria (Plasmodium relictum) at 1,900-m elevation on the Island of Hawaii, with air temperatures too low for sporogony in the vector (Culex quinquefasciatus). On a well-defined site over a 14-year period, 10 of 14 species of native and introduced birds became infected, several epizootics occurred, and the increase in prevalence was driven more by resident species than by mobile species that could have acquired their infections at lower elevations. Greater movement of infectious mosquitoes from lower elevations now permits avian malaria to spread at 1,900 m in Hawaii, in advance of climate warming at that elevation. The increase in malaria at upper elevations due to dispersal of infectious mosquitoes is a real alternative to temperature for the increased incidence of human malaria in tropical highlands.

  1. The Encoding of Sound Source Elevation in the Human Auditory Cortex.

    Science.gov (United States)

    Trapeau, Régis; Schönwiesner, Marc

    2018-03-28

    Spatial hearing is a crucial capacity of the auditory system. While the encoding of horizontal sound direction has been extensively studied, very little is known about the representation of vertical sound direction in the auditory cortex. Using high-resolution fMRI, we measured voxelwise sound elevation tuning curves in human auditory cortex and show that sound elevation is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. We changed the ear shape of participants (male and female) with silicone molds for several days. This manipulation reduced or abolished the ability to discriminate sound elevation and flattened cortical tuning curves. Tuning curves recovered their original shape as participants adapted to the modified ears and regained elevation perception over time. These findings suggest that the elevation tuning observed in low-level auditory cortex did not arise from the physical features of the stimuli but is contingent on experience with spectral cues and covaries with the change in perception. One explanation for this observation may be that the tuning in low-level auditory cortex underlies the subjective perception of sound elevation. SIGNIFICANCE STATEMENT This study addresses two fundamental questions about the brain representation of sensory stimuli: how the vertical spatial axis of auditory space is represented in the auditory cortex and whether low-level sensory cortex represents physical stimulus features or subjective perceptual attributes. Using high-resolution fMRI, we show that vertical sound direction is represented by broad tuning functions preferring lower elevations as well as secondary narrow tuning functions preferring individual elevation directions. In addition, we demonstrate that the shape of these tuning functions is contingent on experience with spectral cues and covaries with the change in perception, which may indicate that the

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

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    Maibritt B Andersen

    Full Text Available Cholinergic, muscarinic receptor agonists exhibit functional dopamine antagonism and muscarinic receptors have been suggested as possible future targets for the treatment of schizophrenia and drug abuse. The muscarinic ligand (5R,6R-6-(3-butylthio-1,2,5-thiadiazol-4-yl-1-azabicyclo[3.2.1]octane (BuTAC exhibits high affinity for muscarinic receptors with no or substantially less affinity for a large number of other receptors and binding sites, including the dopamine receptors and the dopamine transporter. In the present study, we wanted to examine the possible antipsychotic-like effects of BuTAC in primates. To this end, we investigated the effects of BuTAC on d-amphetamine-induced behaviour in antipsychotic-naive Cebus paella monkeys. Possible adverse events of BuTAC, were evaluated in the same monkeys as well as in monkeys sensitized to antipsychotic-induced extrapyramidal side effects. The present data suggests that, the muscarinic receptor ligand BuTAC exhibits antipsychotic-like behaviour in primates. The behavioural data of BuTAC as well as the new biochemical data further substantiate the rationale for the use of muscarinic M1/M2/M4-preferring receptor agonists as novel pharmacological tools in the treatment of schizophrenia.

  3. A comparative psychophysical approach to visual perception in primates.

    Science.gov (United States)

    Matsuno, Toyomi; Fujita, Kazuo

    2009-04-01

    Studies on the visual processing of primates, which have well developed visual systems, provide essential information about the perceptual bases of their higher-order cognitive abilities. Although the mechanisms underlying visual processing are largely shared between human and nonhuman primates, differences have also been reported. In this article, we review psychophysical investigations comparing the basic visual processing that operates in human and nonhuman species, and discuss the future contributions potentially deriving from such comparative psychophysical approaches to primate minds.

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

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    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

  5. 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

  6. A technique to evaluate bone healing in non-human primates using sequential sub(99m)Tc-methylene diphosphonate scintigraphy

    International Nuclear Information System (INIS)

    Dormehl, I.C.

    1982-01-01

    The assessment of bone healing through sequential nuclear medical scintigraphy requires a method of consistent localization of the exact fracture area in each consecutive image as the study progresses. This is difficult when there is surrounding bone activity as in the early stages of trauma, and also if complications should set in. The image profile feature, available from most nuclear medical computer software, facilitates this procedure considerably, as is indicated in the present report on bone healing in baboons. Together with roentgenology and histology a sup(99m)Tc-MDP study was in this way successfully done on the healing of long bone fractures experimentally induced in non-human primates. Different surgical implants were used. The results indicated that sup(99m)Tc-MDP accurately reflects the physiological activity in bone. The time-activity curves obtained are presently being studied together with extensive histology, bearing possible clinical application in mind. (orig.) [de

  7. 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

    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......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...

  8. Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract.

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    Ann M Carias

    2016-09-01

    Full Text Available Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.

  9. Increases in Endogenous or Exogenous Progestins Promote Virus-Target Cell Interactions within the Non-human Primate Female Reproductive Tract.

    Science.gov (United States)

    Carias, Ann M; Allen, Shannon A; Fought, Angela J; Kotnik Halavaty, Katarina; Anderson, Meegan R; Jimenez, Maria L; McRaven, Michael D; Gioia, Casey J; Henning, Tara R; Kersh, Ellen N; Smith, James M; Pereira, Lara E; Butler, Katherine; McNicholl, S Janet M; Hendry, R Michael; Kiser, Patrick F; Veazey, Ronald S; Hope, Thomas J

    2016-09-01

    Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.

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

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    Christina Faust

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Di Cave David

    2011-10-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina, a primate species susceptible to Human Immunodeficiency Virus type 1 infection

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    Jiang Xue-Long

    2009-06-01

    Full Text Available Abstract Background The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1 infection. We have previously reported that the TRIM5-Cyclophilin A (TRIMCyp fusion in pig-tailed macaques (Macaca nemestrina is dysfunctional in restricting HIV-1, which may explain why pig-tailed macaques are susceptible to HIV-1 infection. Similar results have also been reported by other groups. However, according to the current primate taxonomy, the previously reported M. nemestrina are further classified into three species, which all belong to the Macaca spp. This calls for the need to look into the previous studies in more details. Results The local species Northern pig-tailed macaque (M. leonina was analyzed for the correlation of TRIM5 structure and HIV-1 infection. Eleven M. leonina animals were analyzed, and all of them were found to possess TRIM5-CypA fusion at the TRIM5 locus. The transcripts encoding the dysfunctional TRIM5-CypA should result from the G-to-T mutation in the 3'-splicing site of intron 6. Polymorphism in the putative TRIMCyp recognition domain was observed. The peripheral blood mononuclear cells (PBMCs of M. leonina were susceptible to HIV-1 infection. Consistent with the previous results, expression of the M. leonina TRIMCyp in HeLa-T4 cells rendered the cells resistant to HIV-2ROD but not to SIVmac239 infection. Conclusion The susceptibility of M. leonina to HIV-1 infection is due to the dysfunctional TRIM5-CypA fusion in the TRIM5 locus. This finding should broaden our perspective in developing better HIV/AIDS non-human primate animal models.

  14. Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation and Ductal Hyperplasia in Non-Human Primates

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Owston, Michael; Abrahamian, Gregory; La Rosa, Stefano; Marando, Alessandro; Perego, Carla; Di Cairano, Eliana S.; Finzi, Giovanna; Capella, Carlo; Sessa, Fausto; Casiraghi, Francesca; Paez, Ana; Adivi, Ashwin; Davalli, Alberto; Fiorina, Paolo; Guardado Mendoza, Rodolfo; Comuzzie, Anthony G.; Sharp, Mark; DeFronzo, Ralph A.; Halff, Glenn; Dick, Edward J.; Folli, Franco

    2016-01-01

    In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67–positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67–positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67–positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30–positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates. PMID:25447052

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

    Science.gov (United States)

    Burton, Frances D.

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

  16. Donor-Derived Regulatory Dendritic Cell Infusion Maintains Donor-Reactive CD4+CTLA4hi T Cells in Non-Human Primate Renal Allograft Recipients Treated with CD28 Co-Stimulation Blockade

    OpenAIRE

    Mohamed B. Ezzelarab; Lien Lu; William F. Shufesky; Adrian E. Morelli; Adrian E. Morelli; Angus W. Thomson; Angus W. Thomson

    2018-01-01

    Donor-derived regulatory dendritic cell (DCreg) infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag) 4 (CTLA4) and programmed cell death protein 1 (PD1) by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig) is associated with reduced differ...

  17. 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…

  18. Primate beta oscillations and rhythmic behaviors.

    Science.gov (United States)

    Merchant, Hugo; Bartolo, Ramón

    2018-03-01

    The study of non-human primates in complex behaviors such as rhythm perception and entrainment is critical to understand the neurophysiological basis of human cognition. Next to reviewing the role of beta oscillations in human beat perception, here we discuss the role of primate putaminal oscillatory activity in the control of rhythmic movements that are guided by a sensory metronome or internally gated. The analysis of the local field potentials of the behaving macaques showed that gamma-oscillations reflect local computations associated with stimulus processing of the metronome, whereas beta-activity involves the entrainment of large putaminal circuits, probably in conjunction with other elements of cortico-basal ganglia-thalamo-cortical circuit, during internally driven rhythmic tapping. Thus, this review emphasizes the need of parametric neurophysiological observations in non-human primates that display a well-controlled behavior during high-level cognitive processes.

  19. 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. Copyright © 2013 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

    Sundberg, Maria; Bogetofte, Helle; Lawson, Tristan

    2013-01-01

    of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM(+) /CD29(low) sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations......The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and h......ESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation...

  1. Radio frequency-induced temperature elevations in the human head considering small anatomical structures

    International Nuclear Information System (INIS)

    Schmid, G.; Ueberbacher, R.; Samaras, T.

    2007-01-01

    In order to enable a detailed numerical radio frequency (RF) dosimetry and the computations of RF-induced temperature elevations, high-resolution (0.1 mm) numerical models of the human eye, the inner ear organs and the pineal gland were developed and inserted into a commercially available head model. As radiation sources, generic models of handsets at 400, 900 and 1850 MHz operating in close proximity to the head were considered. The results, obtained by finite-difference time domain-based computations, showed a highly heterogeneous specific absorption rate (SAR) distribution and SAR-peaks inside the inner ear structures; however, the corresponding RF-induced temperature elevations were well below 0.1 deg. C, when considering typical output power values of hand-held devices. In case of frontal exposure, with the radiation sources ∼2.5 cm in front of the closed eye, maximum temperature elevations in the eye in the range of ∼0.2-0.6 deg. C were found for typical device output powers. A reduction in tissue perfusion mainly affected the maximum RF-induced temperature elevation of tissues deep inside the head. Similarly, worst-case considerations regarding pulsed irradiation affected temperature elevations in deep tissue significantly more than in superficial tissues. (authors)

  2. Human-nonhuman primate interactions amongst Tikuna people: perceptions and local initiatives for resource management in Amacayacu in the Colombian Amazon.

    Science.gov (United States)

    Parathian, Hannah E; Maldonado, Angela M

    2010-09-01

    This study assesses the impact of hunting on the densities of nonhuman primates in two indigenous Tikuna territories (Mocagua and San Martín), overlapping Amacayacu National Park in the Colombian Amazon. Large-bodied primates were once favored prey by Tikunas, but are now rarely hunted owing to the diminishing primate populations. We evaluate the effect of a hunting ban on woolly monkeys (Lagothrix lagothricha) by the residents of Mocagua, using qualitative and quantitative methods. Hunting records showed that from February 2005 to February 2009, a total of 25,142 kg of mammal bushmeat were harvested in Mocagua and San Martín. Primates constituted 345 kg of the total harvest. From 223 kg of large-bodied primates extracted for subsistence purposes, 160 kg were hunted in San Martín and 64 kg in Mocagua. Large-bodied primates made up 70% of the total primate biomass in Mocagua (398 kg/km(2)) and 22% in San Martín (199 kg/km(2)). From dietary records, we found bushmeat constituted 30% of protein consumption in Mocagua and 37% in San Martín. Primates were absent in records from Mocagua, and appeared only three times in those from San Martín suggesting inconsistencies with hunting data. Despite its moderate consumption, bushmeat was identified as a highly valued food source during focus group activities. Primate pet-keeping and part utilization were observed in San Martín but not in Mocagua, possibly as a consequence of fewer primates being hunted. We suggest that Mocagua provides an example of how community-based conservation strategies can be achieved, where opportunities for employment in tourism and alternative food sources are available. 2010 Wiley-Liss, Inc.

  3. Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates.

    Science.gov (United States)

    Nevins, Myron; Al Hezaimi, Khalid; Schupbach, Peter; Karimbux, Nadeem; Kim, David M

    2012-07-01

    This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet-derived growth factor-BB (rhPDGF-BB), to augment localized posterior mandibular defects in non-human primates (Papio hamadryas). Bilateral critical-sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non-human primate. All sites exhibited vertical ridge augmentation, with physiologic hard- and soft-tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non-significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF-BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical-sized defects. This investigation supplies additional evidence that eHAC blocks infused with rhPDGF-BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. 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

    Science.gov (United States)

    Casiraghi, Francesca; Chavez, Alberto O.; Davalli, Alberto M.; Naegelin, Terry; Comuzzie, Anthony G.; Frost, Patricia; Musi, Nicolas; Folli, Franco

    2013-01-01

    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. PMID:24069218

  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.

    Science.gov (United States)

    Casiraghi, Francesca; Lertwattanarak, Raweewan; Luzi, Livio; Chavez, Alberto O; Davalli, Alberto M; Naegelin, Terry; Comuzzie, Anthony G; Frost, Patricia; Musi, Nicolas; Folli, Franco

    2013-01-01

    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. 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. 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. 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. 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.

  8. 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.

  9. 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

    Directory of Open Access Journals (Sweden)

    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.

  10. Eomesoderminlo CTLA4hi Alloreactive CD8+ Memory T Cells Are Associated With Prolonged Renal Transplant Survival Induced by Regulatory Dendritic Cell Infusion in CTLA4Ig-Treated Non-Human Primates

    Science.gov (United States)

    Ezzelarab, Mohamed B.; Lu, Lien; Guo, Hao; Zahorchak, Alan F.; Shufesky, William F.; Cooper, David K.C.; Morelli, Adrian E.; Thomson, Angus W.

    2015-01-01

    Background Memory T cells (Tmem), particularly those resistant to costimulation blockade (CB), are a major barrier to transplant tolerance. The transcription factor Eomesodermin (Eomes) is critical for Tmem development and maintenance, but its expression by alloactivated T cells has not been examined in non-human primates. Methods We evaluated Eomes and co-inhibitory cytotoxic T lymphocyte antigen-4 (CTLA4) expression by alloactivated rhesus monkey T cells in the presence of CTLA4 immunoglobulin (Ig), both in vitro and in renal allograft recipients treated with CTLA4Ig, with or without regulatory dendritic cell (DCreg) infusion. Results In normal monkeys, CD8+ T cells expressed significantly more Eomes than CD4+T cells. By contrast, CD8+T cells displayed minimal CTLA4. Among T cell subsets, central Tmem (Tcm) expressed the highest levels of Eomes. Notably, EomesloCTLA4hi cells displayed higher levels of CD25 and Foxp3 than EomeshiCTLA4lo CD8+ T cells. Following allostimulation, distinct proliferating EomesloCTLA4hi and EomeshiCTLA4lo CD8+ T cell populations were identified, with a high proportion of Tcm being EomesloCTLA4hi. CB with CTLA4Ig during allostimulation of CD8+T cells reduced CTLA4 but not Eomes expression, significantly reducing EomesloCTLA4hi cells. After transplantation with CB and rapamycin, donor-reactive EomesloCTLA4hi CD8+T cells were reduced. However, in monkeys also given DCreg, absolute numbers of these cells were elevated significantly. Conclusions Low Eomes and high CTLA4 expression by donor-reactive CD8+ Tmem is associated with prolonged renal allograft survival induced by DCreg infusion in CTLA4Ig-treated monkeys. Prolonged allograft survival associated with DCreg infusion may be related to maintenance of donor-reactive EomesloCTLA4hi Tcm. PMID:26680373

  11. Culture in Animals: The Case of a Non-human Primate Culture of Low Aggression and High Affiliation

    Science.gov (United States)

    Sapolsky, Robert M.

    2006-01-01

    Philosophers often consider what it is that makes individuals human. For biologists considering the same, the answer is often framed in the context of what are the key differences between humans and other animals. One vestige of human uniqueness still often cited by anthropologists is culture. However, this notion has been challenged in recent…

  12. Human-specific SNP in obesity genes, adrenergic receptor beta2 (ADRB2, Beta3 (ADRB3, and PPAR γ2 (PPARG, during primate evolution.

    Directory of Open Access Journals (Sweden)

    Akiko Takenaka

    Full Text Available UNLABELLED: Adrenergic-receptor beta2 (ADRB2 and beta3 (ADRB3 are obesity genes that play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. The Glu27 allele in ADRB2 and the Arg64 allele in ADRB3 are associated with abdominal obesity and early onset of non-insulin-dependent diabetes mellitus (NIDDM in many ethnic groups. Peroxisome proliferator-activated receptor γ (PPARG is required for adipocyte differentiation. Pro12Ala mutation decreases PPARG activity and resistance to NIDDM. In humans, energy-expense alleles, Gln27 in ADRB2 and Trp64 in ADRB3, are at higher frequencies than Glu27 and Arg64, respectively, but Ala12 in PPARG is at lower frequency than Pro12. Adaptation of humans for lipolysis, thermogenesis, and reduction of fat accumulation could be considered by examining which alleles in these genes are dominant in non-human primates (NHP. All NHP (P. troglodytes, G. gorilla, P. pygmaeus, H. agilis and macaques had energy-thrifty alleles, Gly16 and Glu27 in ADRB2, and Arg64 in ADRB3, but did not have energy-expense alleles, Arg16, Gln27 and Trp64 alleles. In PPARG gene, all NHP had large adipocyte accumulating type, the Pro12 allele. CONCLUSIONS: These results indicate that a tendency to produce much more heat through the energy-expense alleles developed only in humans, who left tropical rainforests for savanna and developed new features in their heat-regulation systems, such as reduction of body hair and increased evaporation of water, and might have helped the protection of entrails from cold at night, especially in glacial periods.

  13. Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

    Science.gov (United States)

    Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

    2002-01-01

    To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by 0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.

  14. 78 FR 11521 - Control of Communicable Disease; Foreign-Requirements for Importers of Nonhuman Primates (NHP)

    Science.gov (United States)

    2013-02-15

    ... Part 71 Control of Communicable Disease; Foreign--Requirements for Importers of Nonhuman Primates (NHP... Primates (NHP) AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human... live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca...

  15. Temperature elevation in the eye of anatomically based human head models for plane-wave exposures

    International Nuclear Information System (INIS)

    Hirata, A; Watanabe, S; Fujiwara, O; Kojima, M; Sasaki, K; Shiozawa, T

    2007-01-01

    This study investigated the temperature elevation in the eye of anatomically based human head models for plane-wave exposures. The finite-difference time-domain method is used for analyzing electromagnetic absorption and temperature elevation. The eyes in the anatomic models have average dimensions and weight. Computational results show that the ratio of maximum temperature in the lens to the eye-average SAR (named 'heating factor for the lens') is almost uniform (0.112-0.147 deg. C kg W -1 ) in the frequency region below 3 GHz. Above 3 GHz, this ratio increases gradually with an increase of frequency, which is attributed to the penetration depth of an electromagnetic wave. Particular attention is paid to the difference in the heating factor for the lens between this study and earlier works. Considering causes clarified in this study, compensated heating factors in all these studies are found to be in good agreement

  16. Molecular and immunological tools for the evaluation of the cellular immune response in the neotropical monkey Saimiri sciureus, a non-human primate model for malaria research.

    Science.gov (United States)

    Riccio, Evelyn K P; Pratt-Riccio, Lilian R; Bianco-Júnior, Cesare; Sanchez, Violette; Totino, Paulo R R; Carvalho, Leonardo J M; Daniel-Ribeiro, Cláudio Tadeu

    2015-04-18

    The neotropical, non-human primates (NHP) of the genus Saimiri and Aotus are recommended by the World Health Organization as experimental models for the study of human malaria because these animals can be infected with the same Plasmodium that cause malaria in humans. However, one limitation is the lack of immunological tools to assess the immune response in these models. The present study focuses on the development and comparative use of molecular and immunological methods to evaluate the cellular immune response in Saimiri sciureus. Blood samples were obtained from nineteen uninfected Saimiri. Peripheral blood mononuclear cells (PBMC) from these animals and splenocytes from one splenectomized animal were cultured for 6, 12, 18, 24, 48, 72 and 96 hrs in the presence of phorbol-12-myristate-13-acetate and ionomycin. The cytokine levels in the supernatant were detected using human and NHP cytometric bead array Th1/Th2 cytokine kits, the Bio-Plex Pro Human Cytokine Th1/Th2 Assay, enzyme-linked immunosorbent assay, enzyme-linked immunospot assays and intracellular cytokine secretion assays. Cytokine gene expression was examined through TaqMan® Gene Expression Real-Time PCR using predesigned human gene-specific primers and probes or primers and probes designed based on published S. sciureus cytokine sequences. The use of five assays based on monoclonal antibodies specific for human cytokines facilitated the detection of IL-2, IL-4 and/or IFN-γ. TaqMan array plates facilitated the detection of 12 of the 28 cytokines assayed. However, only seven cytokines (IL-1A, IL-2, IL-10, IL-12B, IL-17, IFN-β, and TNF) presented relative expression levels of at least 70% of the gene expression observed in human PBMC. The use of primers and probes specific for S. sciureus cytokines facilitated the detection of transcripts that showed relative expression below the threshold of 70%. The most efficient evaluation of cytokine gene expression, in PBMC and splenocytes, was observed

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

    Science.gov (United States)

    Vailas, Arthur C.; Martinez, Daniel A.

    1999-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jacqueline R. Thompson

    2017-07-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  20. Changes in Cerebral Blood Flow during an Alteration in Glycemic State in a Large Non-human Primate (Papio hamadryas sp.).

    Science.gov (United States)

    Kochunov, Peter; Wey, Hsiao-Ying; Fox, Peter T; Lancaster, Jack L; Davis, Michael D; Wang, Danny J J; Lin, Ai-Ling; Bastarrachea, Raul A; Andrade, Marcia C R; Mattern, Vicki; Frost, Patrice; Higgins, Paul B; Comuzzie, Anthony G; Voruganti, Venkata S

    2017-01-01

    Changes in cerebral blood flow (CBF) during a hyperglycemic challenge were mapped, using perfusion-weighted MRI, in a group of non-human primates. Seven female baboons were fasted for 16 h prior to 1-h imaging experiment, performed under general anesthesia, that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500 mg/kg). CBF maps were collected every 7 s and blood glucose and insulin levels were sampled at regular intervals. Blood glucose levels rose from 51.3 ± 10.9 to 203.9 ± 38.9 mg/dL and declined to 133.4 ± 22.0 mg/dL, at the end of the experiment. Regional CBF changes consisted of four clusters: cerebral cortex, thalamus, hypothalamus, and mesencephalon. Increases in the hypothalamic blood flow occurred concurrently with the regulatory response to systemic glucose change, whereas CBF declined for other clusters. The return to baseline of hypothalamic blood flow was observed while CBF was still increasing in other brain regions. The spatial pattern of extra-hypothalamic CBF changes was correlated with the patterns of several cerebral networks including the default mode network. These findings suggest that hypothalamic blood flow response to systemic glucose levels can potentially be explained by regulatory activity. The response of extra-hypothalamic clusters followed a different time course and its spatial pattern resembled that of the default-mode network.

  1. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

    Science.gov (United States)

    Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

    2008-08-01

    Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Jeffrey R Kugelman

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

  4. 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. © 2014 Wiley Periodicals, Inc.

  5. A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates.

    Science.gov (United States)

    Padte, Neal N; Boente-Carrera, Mar; Andrews, Chasity D; McManus, Jenny; Grasperge, Brooke F; Gettie, Agegnehu; Coelho-dos-Reis, Jordana G; Li, Xiangming; Wu, Douglass; Bruder, Joseph T; Sedegah, Martha; Patterson, Noelle; Richie, Thomas L; Wong, Chi-Huey; Ho, David D; Vasan, Sandhya; Tsuji, Moriya

    2013-01-01

    A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP) model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA), consists of two non-replicating recombinant adenoviral (Ad) vectors, one expressing the circumsporozoite protein (CSP) and another expressing the apical membrane antigen-1 (AMA1) of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM) immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold) in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.

  6. A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates.

    Directory of Open Access Journals (Sweden)

    Neal N Padte

    Full Text Available A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer, enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA, consists of two non-replicating recombinant adenoviral (Ad vectors, one expressing the circumsporozoite protein (CSP and another expressing the apical membrane antigen-1 (AMA1 of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.

  7. Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry

    Science.gov (United States)

    Chen, Zhidan; Coy, Stephen L.; Pannkuk, Evan L.; Laiakis, Evagelia C.; Hall, Adam B.; Fornace, Albert J.; Vouros, Paul

    2016-10-01

    Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure.

  8. Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents

    DEFF Research Database (Denmark)

    Khetarpal, Sumeet A; Schjoldager, Katrine T; Christoffersen, Christina

    2016-01-01

    Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian mod...

  9. The comparative anatomy of the forelimb veins of primates.

    OpenAIRE

    Thiranagama, R; Chamberlain, A T; Wood, B A

    1989-01-01

    One hundred and thirteen forelimbs taken from 62 individuals belonging to 17 primate genera were dissected to reveal the entire course of the superficial venous system. The course of the deep venous system was also documented in at least one forelimb of each primate genus, and the number and location of perforating veins was recorded in 18 human and 45 non-human primate limbs. In Pan, Gorilla and in about 25% of human specimens the lateral superficial vein was confined to the forearm, while i...

  10. Conservation of myeloid surface antigens on primate granulocytes.

    Science.gov (United States)

    Letvin, N L; Todd, R F; Palley, L S; Schlossman, S F; Griffin, J D

    1983-02-01

    Monoclonal antibodies reactive with myeloid cell surface antigens were used to study evolutionary changes in granulocyte surface antigens from primate species. Certain of these granulocyte membrane antigens are conserved in phylogenetically distant species, indicating the potential functional importance of these structures. The degree of conservation of these antigens reflects the phylogenetic relationship between primate species. Furthermore, species of the same genus show similar patterns of binding to this panel of anti-human myeloid antibodies. This finding of conserved granulocyte surface antigens suggests that non-human primates may provide a model system for exploring uses of monoclonal antibodies in the treatment of human myeloid disorders.

  11. A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

    Science.gov (United States)

    Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

    2016-07-01

    Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Masanori Sasaki

    Full Text Available Most experimental stroke research is carried out in rodents, but given differences between rodents and human, nonhuman primate (NHP models may provide a valuable tool to study therapeutic interventions. The authors developed a surgical method for transient occlusion of the M1 branch of middle cerebral artery (MCA in the African green monkey to evaluate safety aspects of intravenous infusion of mesenchymal stem cells (hMSCs derived from human bone marrow.The left Sylvian fissure was exposed by a small fronto-temporal craniotomy. The M1 branch of the MCA was exposed by microsurgical dissection and clipped for 2 to 4 hours. Neurological examinations and magnetic resonance imaging (MRI were carried out at regular post-operative course. hMSCs were infused 1 hour after reperfusion (clip release in the 3-hour occlusion model.During M1 occlusion, two patterns of changes were observed in the lateral hemisphere surface. One pattern (Pattern 1 was darkening of venous blood, small vessel collapse, and blood pooling with no venous return in cortical veins. Animals with these three features had severe and lasting hemiplegia and MRI demonstrated extensive MCA territory infarction. Animals in the second pattern (Pattern 2 displayed darkening of venous blood, small vessel collapse, and reduced but incompletely occluded venous flow and the functional deficit was much less severe and MRI indicated smaller infarction areas in brain. The severe group (Pattern 1 likely had less extensive collateral circulation than the less severe group (Pattern 2 where venous pooling of blood was not observed. The hMSC infused animals showed a trend for greater functional improvement that was not statistically significant in the acute phase and no additive negative effects.These results indicate inter-animal variability of collateral circulation after complete M1 occlusion and that hMSC infusion is safe in the developed NHP stroke model.

  13. Modeling Elevation Equilibrium and Human Adaptation in the Ganges-Brahmaputra Delta

    Science.gov (United States)

    Tasich, C. M.; Gilligan, J. M.; Goodbred, S. L., Jr.; Hale, R. P.; Wilson, C.

    2017-12-01

    The communities living in the low-lying tidal reaches of the Ganges-Brahmaputra delta rely on a system of polders (earthen-embanked landscapes) to prevent against tidal inundation and storm surge. These communities initially thrived as a result of poldering due to the increase in the total arable land, which presently helps sustain a population of 20 million people. However, poldering led to the unintended consequence of reducing water and sediment exchange between the polders and the tidal network, which has resulted in a significant elevation offset of 1-1.5 m relative to that of the natural landscape. This offset causes significant waterlogging which is problematic for rice cultivation. Engineering solutions, such as Tidal River Management (TRM), have been proposed to help alleviate this offset. Previous work suggests with proper implementation of TRM, polder elevations can successfully be reequilibrated to that of the natural elevation on timescales of 5-20 years. However, TRM implementation requires community commitment to allowing controlled tidal inundation. Here, we expand previous numerical simulations of sediment accumulation through field-based constraints of grain size, compaction, and sea level rise. We then model human decision-making for implementation of TRM practices using an agent-based model. Our sediment model employs a mass balance of sediment accumulation as a function of tidal height, suspended sediment concentration, settling velocity, and dry bulk density. We couple this sediment model to an agent-based model of human decision making. We model a hypothetical 500 x 300 m polder community with the lowest elevations in the middle and the highest elevations adjacent to the tidal channels. Landowners assess their risk and profit for future scenarios with and without TRM. All landowner decisions are aggregated and then a community decision is made on whether to implement TRM. Initial findings suggest that basic voting (majority rule) results in

  14. 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.

  15. Three-dimensional primate molar enamel thickness.

    Science.gov (United States)

    Olejniczak, Anthony J; Tafforeau, Paul; Feeney, Robin N M; Martin, Lawrence B

    2008-02-01

    Molar enamel thickness has played an important role in the taxonomic, phylogenetic, and dietary assessments of fossil primate teeth for nearly 90 years. Despite the frequency with which enamel thickness is discussed in paleoanthropological discourse, methods used to attain information about enamel thickness are destructive and record information from only a single plane of section. Such semidestructive planar methods limit sample sizes and ignore dimensional data that may be culled from the entire length of a tooth. In light of recently developed techniques to investigate enamel thickness in 3D and the frequent use of enamel thickness in dietary and phylogenetic interpretations of living and fossil primates, the study presented here aims to produce and make available to other researchers a database of 3D enamel thickness measurements of primate molars (n=182 molars). The 3D enamel thickness measurements reported here generally agree with 2D studies. Hominoids show a broad range of relative enamel thicknesses, and cercopithecoids have relatively thicker enamel than ceboids, which in turn have relatively thicker enamel than strepsirrhine primates, on average. Past studies performed using 2D sections appear to have accurately diagnosed the 3D relative enamel thickness condition in great apes and humans: Gorilla has the relatively thinnest enamel, Pan has relatively thinner enamel than Pongo, and Homo has the relatively thickest enamel. Although the data set presented here has some taxonomic gaps, it may serve as a useful reference for researchers investigating enamel thickness in fossil taxa and studies of primate gnathic biology.

  16. Primates in peril: the significance of Brazil, Madagascar, Indonesia and the Democratic Republic of the Congo for global primate conservation

    Science.gov (United States)

    Mittermeier, Russell A.; Wich, Serge; Gouveia, Sidney; Dobrovolski, Ricardo; Nijman, Vincent; Rylands, Anthony B.; Johnson, Steig; Rodrigues de Melo, Fabiano; Schwitzer, Christoph; Roos, Christian; Cheyne, Susan M.; Martins Kierulff, Maria Cecilia; Raharivololona, Brigitte; Ratsimbazafy, Jonah; Supriatna, Jatna; Boonratana, Ramesh; Wedana, Made; Setiawan, Arif

    2018-01-01

    Primates occur in 90 countries, but four—Brazil, Madagascar, Indonesia, and the Democratic Republic of the Congo (DRC)—harbor 65% of the world’s primate species (439) and 60% of these primates are Threatened, Endangered, or Critically Endangered (IUCN Red List of Threatened Species 2017-3). Considering their importance for global primate conservation, we examine the anthropogenic pressures each country is facing that place their primate populations at risk. Habitat loss and fragmentation are main threats to primates in Brazil, Madagascar, and Indonesia. However, in DRC hunting for the commercial bushmeat trade is the primary threat. Encroachment on primate habitats driven by local and global market demands for food and non-food commodities hunting, illegal trade, the proliferation of invasive species, and human and domestic-animal borne infectious diseases cause habitat loss, population declines, and extirpation. Modeling agricultural expansion in the 21st century for the four countries under a worst-case-scenario, showed a primate range contraction of 78% for Brazil, 72% for Indonesia, 62% for Madagascar, and 32% for DRC. These pressures unfold in the context of expanding human populations with low levels of development. Weak governance across these four countries may limit effective primate conservation planning. We examine landscape and local approaches to effective primate conservation policies and assess the distribution of protected areas and primates in each country. Primates in Brazil and Madagascar have 38% of their range inside protected areas, 17% in Indonesia and 14% in DRC, suggesting that the great majority of primate populations remain vulnerable. We list the key challenges faced by the four countries to avert primate extinctions now and in the future. In the short term, effective law enforcement to stop illegal hunting and illegal forest destruction is absolutely key. Long-term success can only be achieved by focusing local and global public

  17. Primates in peril: the significance of Brazil, Madagascar, Indonesia and the Democratic Republic of the Congo for global primate conservation.

    Science.gov (United States)

    Estrada, Alejandro; Garber, Paul A; Mittermeier, Russell A; Wich, Serge; Gouveia, Sidney; Dobrovolski, Ricardo; Nekaris, K A I; Nijman, Vincent; Rylands, Anthony B; Maisels, Fiona; Williamson, Elizabeth A; Bicca-Marques, Julio; Fuentes, Agustin; Jerusalinsky, Leandro; Johnson, Steig; Rodrigues de Melo, Fabiano; Oliveira, Leonardo; Schwitzer, Christoph; Roos, Christian; Cheyne, Susan M; Martins Kierulff, Maria Cecilia; Raharivololona, Brigitte; Talebi, Mauricio; Ratsimbazafy, Jonah; Supriatna, Jatna; Boonratana, Ramesh; Wedana, Made; Setiawan, Arif

    2018-01-01

    Primates occur in 90 countries, but four-Brazil, Madagascar, Indonesia, and the Democratic Republic of the Congo (DRC)-harbor 65% of the world's primate species (439) and 60% of these primates are Threatened, Endangered, or Critically Endangered (IUCN Red List of Threatened Species 2017-3). Considering their importance for global primate conservation, we examine the anthropogenic pressures each country is facing that place their primate populations at risk. Habitat loss and fragmentation are main threats to primates in Brazil, Madagascar, and Indonesia. However, in DRC hunting for the commercial bushmeat trade is the primary threat. Encroachment on primate habitats driven by local and global market demands for food and non-food commodities hunting, illegal trade, the proliferation of invasive species, and human and domestic-animal borne infectious diseases cause habitat loss, population declines, and extirpation. Modeling agricultural expansion in the 21st century for the four countries under a worst-case-scenario, showed a primate range contraction of 78% for Brazil, 72% for Indonesia, 62% for Madagascar, and 32% for DRC. These pressures unfold in the context of expanding human populations with low levels of development. Weak governance across these four countries may limit effective primate conservation planning. We examine landscape and local approaches to effective primate conservation policies and assess the distribution of protected areas and primates in each country. Primates in Brazil and Madagascar have 38% of their range inside protected areas, 17% in Indonesia and 14% in DRC, suggesting that the great majority of primate populations remain vulnerable. We list the key challenges faced by the four countries to avert primate extinctions now and in the future. In the short term, effective law enforcement to stop illegal hunting and illegal forest destruction is absolutely key. Long-term success can only be achieved by focusing local and global public

  18. Contributions of Nonhuman Primates to Research on Aging.

    Science.gov (United States)

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

    2016-03-01

    Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. © The Author(s) 2016.

  19. Persistent neural activity in auditory cortex is related to auditory working memory in humans and nonhuman primates.

    Science.gov (United States)

    Huang, Ying; Matysiak, Artur; Heil, Peter; König, Reinhard; Brosch, Michael

    2016-07-20

    Working memory is the cognitive capacity of short-term storage of information for goal-directed behaviors. Where and how this capacity is implemented in the brain are unresolved questions. We show that auditory cortex stores information by persistent changes of neural activity. We separated activity related to working memory from activity related to other mental processes by having humans and monkeys perform different tasks with varying working memory demands on the same sound sequences. Working memory was reflected in the spiking activity of individual neurons in auditory cortex and in the activity of neuronal populations, that is, in local field potentials and magnetic fields. Our results provide direct support for the idea that temporary storage of information recruits the same brain areas that also process the information. Because similar activity was observed in the two species, the cellular bases of some auditory working memory processes in humans can be studied in monkeys.

  20. Whole-genome characterization in pedigreed non-human primates using Genotyping-By-Sequencing and imputation.

    OpenAIRE

    Cervera-Juanes, Rita; Vinson, Amanda; Ferguson, Betsy; Carbone, Lucia; Spindel, Eliot; Mccouch, Susan; Spindel, Jennifer; Nevonen, Kimberly; Letaw, John; Raboin, Michael; Bimber, Ben

    2016-01-01

    Background: Rhesus macaques are widely used in biomedical research, but the application of genomic information in this species to better understand human disease is still undeveloped. Whole-genome sequence (WGS) data in pedigreed macaque colonies could provide substantial experimental power, but the collection of WGS data in large cohorts remains a formidable expense. Here, we describe a cost-effective approach that selects the most informative macaques in a pedigree for whole-genome sequenci...

  1. Taxonomy proposal for Old World monkey adenoviruses: characterisation of several non-human, non-ape primate adenovirus lineages.

    Science.gov (United States)

    Pantó, Laura; Podgorski, Iva I; Jánoska, Máté; Márkó, Orsolya; Harrach, Balázs

    2015-12-01

    A species classification regarding Old World monkey adenoviruses is proposed. We determined the nucleotide sequences of PCR-amplified fragments from the genes of the IVa2, DNA-dependent DNA polymerase, penton base, and hexon proteins from every simian adenovirus (SAdV) serotype that originated from Old World monkeys for which the full genome sequence had not yet been published. We confirmed that the majority of Old Word monkey SAdVs belong to two previously established species. Interestingly, one is the most recently established human AdV species, Human mastadenovirus G, which includes a single human virus, HAdV-52, as well as SAdV-1, -2, -7, -11, -12, and -15. The other approved species, Simian mastadenovirus A includes SAdV-3, -4, -6, -9, -10, -14, and -48. Several SAdVs (SAdV-5, -8, -49, -50) together with baboon AdV-1 and rhesus monkey AdV strains A1139, A1163, A1173, A1258, A1285, A1296, A1312, A1327 and A1335 have been proposed to be classified into an additional species, Simian mastadenovirus B. Another proposed species, Simian mastadenovirus C has been described for SAdV-19, baboon AdV-2/4 and -3. Our study revealed the existence of four additional AdV lineages. The corresponding new candidate species are Simian mastadenovirus D (for SAdV-13), Simian mastadenovirus E (for SAdV-16), Simian mastadenovirus F (for SAdV-17 and -18), and Simian mastadenovirus G (for SAdV-20). Several biological and genomic properties, such as the host origin, haemagglutination profile, number of fibre genes, and G+C content of the genome, strongly support this classification. Three SAdV strains originating from the American Type Culture Collection turned out to be mixtures of at least two virus types, either of the same species (SAdV-12 and -15 types from Human mastadenovirus G) or of two different species (SAdV-5 types from Simian mastadenovirus B and Human mastadenovirus G).

  2. Hands of early primates.

    Science.gov (United States)

    Boyer, Doug M; Yapuncich, Gabriel S; Chester, Stephen G B; Bloch, Jonathan I; Godinot, Marc

    2013-12-01

    Questions surrounding the origin and early evolution of primates continue to be the subject of debate. Though anatomy of the skull and inferred dietary shifts are often the focus, detailed studies of postcrania and inferred locomotor capabilities can also provide crucial data that advance understanding of transitions in early primate evolution. In particular, the hand skeleton includes characteristics thought to reflect foraging, locomotion, and posture. Here we review what is known about the early evolution of primate hands from a comparative perspective that incorporates data from the fossil record. Additionally, we provide new comparative data and documentation of skeletal morphology for Paleogene plesiadapiforms, notharctines, cercamoniines, adapines, and omomyiforms. Finally, we discuss implications of these data for understanding locomotor transitions during the origin and early evolutionary history of primates. Known plesiadapiform species cannot be differentiated from extant primates based on either intrinsic hand proportions or hand-to-body size proportions. Nonetheless, the presence of claws and a different metacarpophalangeal [corrected] joint form in plesiadapiforms indicate different grasping mechanics. Notharctines and cercamoniines have intrinsic hand proportions with extremely elongated proximal phalanges and digit rays relative to metacarpals, resembling tarsiers and galagos. But their hand-to-body size proportions are typical of many extant primates (unlike those of tarsiers, and possibly Teilhardina, which have extremely large hands). Non-adapine adapiforms and omomyids exhibit additional carpal features suggesting more limited dorsiflexion, greater ulnar deviation, and a more habitually divergent pollex than observed plesiadapiforms. Together, features differentiating adapiforms and omomyiforms from plesiadapiforms indicate increased reliance on vertical prehensile-clinging and grasp-leaping, possibly in combination with predatory behaviors in

  3. Intron-exon organization of the active human protein S gene PS. alpha. and its pseudogene PS. beta. : Duplication and silencing during primate evolution

    Energy Technology Data Exchange (ETDEWEB)

    Ploos van Amstel, H.; Reitsma, P.H.; van der Logt, C.P.; Bertina, R.M. (University Hospital, Leiden (Netherlands))

    1990-08-28

    The human protein S locus on chromosome 3 consists of two protein S genes, PS{alpha} and PS{beta}. Here the authors report the cloning and characterization of both genes. Fifteen exons of the PS{alpha} gene were identified that together code for protein S mRNA as derived from the reported protein S cDNAs. Analysis by primer extension of liver protein S mRNA, however, reveals the presence of two mRNA forms that differ in the length of their 5{prime}-noncoding region. Both transcripts contain a 5{prime}-noncoding region longer than found in the protein S cDNAs. The two products may arise from alternative splicing of an additional intron in this region or from the usage of two start sites for transcription. The intron-exon organization of the PS{alpha} gene fully supports the hypothesis that the protein S gene is the product of an evolutional assembling process in which gene modules coding for structural/functional protein units also found in other coagulation proteins have been put upstream of the ancestral gene of a steroid hormone binding protein. The PS{beta} gene is identified as a pseudogene. It contains a large variety of detrimental aberrations, viz., the absence of exon I, a splice site mutation, three stop codons, and a frame shift mutation. Overall the two genes PS{alpha} and PS{beta} show between their exonic sequences 96.5% homology. Southern analysis of primate DNA showed that the duplication of the ancestral protein S gene has occurred after the branching of the orangutan from the African apes. A nonsense mutation that is present in the pseudogene of man also could be identified in one of the two protein S genes of both chimpanzee and gorilla. This implicates that silencing of one of the two protein S genes must have taken place before the divergence of the three African apes.

  4. Impaired control of body cooling during heterothermia represents the major energetic constraint in an aging non-human primate exposed to cold.

    Directory of Open Access Journals (Sweden)

    Jeremy Terrien

    2009-10-01

    Full Text Available Daily heterothermia is used by small mammals for energy and water savings, and seems to be preferentially exhibited during winter rather than during summer. This feature induces a trade-off between the energy saved during daily heterothermia and the energy cost of arousal, which can impact energy balance and survival under harsh environmental conditions. Especially, aging may significantly affect such trade off during cold-induced energy stress, but direct evidences are still lacking. We hypothesized that aging could alter the energetics of daily heterothermia, and that the effects could differ according to season. In the gray mouse lemur (Microcebus murinus, a non-human primate species which exhibits daily heterothermia, we investigated the effects of exposures to 25 and 12 degrees C on body composition, energy balance, patterns of heterothermia and water turnover in adult (N = 8 and aged animals (N = 7 acclimated to winter-like or summer-like photoperiods. Acclimation to summer prevented animals from deep heterothermia, even during aging. During winter, adult animals at 12 degrees C and aged animals at 25 degrees C exhibited low levels of energy expenditure with minor modulations of heterothermia. The major effects of cold were observed during winter, and were particularly pronounced in aged mouse lemurs which exhibited deep heterothermia phases. Body composition was not significantly affected by age and could not explain the age-related differences in heterothermia patterns. However, aging was associated with increased levels of energy expenditure during cold exposure, in concomitance with impaired energy balance. Interestingly, increased energy expenditure and depth of heterothermia phases were strongly correlated. In conclusion, it appeared that the exhibition of shallow heterothermia allowed energy savings during winter in adult animals only. Aged animals exhibited deep heterothermia and increased levels of energy expenditure, impairing

  5. The use of discriminant analysis for evaluation of early-response multiple biomarkers of radiation exposure using non-human primate 6-Gy whole-body radiation model

    Energy Technology Data Exchange (ETDEWEB)

    Ossetrova, N.I. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: ossetrova@afrri.usuhs.mil; Farese, A.M.; MacVittie, T.J. [Marlene and Stewart Greenebaum Cancer Center, Bressler Research Building, Room 7-039, University of Maryland-Baltimore, 655 West Baltimore Street, Baltimore, MD 21201 (United States); Manglapus, G.L.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    The present need to rapidly identify severely irradiated individuals in mass-casualty and population-monitoring scenarios prompted an evaluation of potential protein biomarkers to provide early diagnostic information after exposure. The level of specific proteins measured using immunodiagnostic technologies may be useful as protein biomarkers to provide early diagnostic information for acute radiation exposures. Herein we present results from on-going studies using a non-human primate (NHP) 6-Gy X-rays ( 0.13Gymin{sup -1}) whole-body radiation model. Protein targets were measured by enzyme-linked immunosorbent assay (ELISA) in blood plasma before, 1, and 2 days after exposure. Exposure of 10 NHPs to 6 Gy resulted in the up-regulation of plasma levels of (a) p21 WAF1/CIP1, (b) interleukin 6 (IL-6), (c) tissue enzyme salivary {alpha}-amylase, and (d) C-reactive protein. Data presented show the potential utility of protein biomarkers selected from distinctly different pathways to detect radiation exposure. A correlation analysis demonstrated strong correlations among different combinations of four candidate radiation-responsive blood protein biomarkers. Data analyzed with use of multivariate discriminant analysis established very successful separation of NHP groups: 100% discrimination power for animals with correct classification for separation between groups before and 1 day after irradiation, and 95% discrimination power for separation between groups before and 2 days after irradiation. These results also demonstrate proof-in-concept that multiple protein biomarkers provide early diagnostic information to the medical community, along with classical biodosimetric methodologies, to effectively manage radiation casualty incidents.

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

    Science.gov (United States)

    Downs, Matthew E; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Teichert, Tobias; Chen, Shangshang; Konofagou, Elisa E; Ferrera, Vincent P

    2015-01-01

    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.

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

    Science.gov (United States)

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

    2017-06-01

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

  8. Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate

    Science.gov (United States)

    Velikyan, Irina; Lindhe, Örjan

    2018-01-01

    Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced 68Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to αvβ3 integrin receptors. The main objective of this study was to develop a method for 68Ga-labeling of RGD containing bicyclic octapeptide ([68Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [68Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full 68Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [68Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis. PMID:29531858

  9. Advancing research in regeneration and repair of the motor circuitry: non-human primate models and imaging scales as the missing links for successfully translating injectable therapeutics to the clinic.

    Science.gov (United States)

    Tsintou, Magdalini; Dalamagkas, Kyriakos; Makris, Nikos

    2016-01-01

    Regeneration and repair is the ultimate goal of therapeutics in trauma of the central nervous system (CNS). Stroke and spinal cord injury (SCI) are two highly prevalent CNS disorders that remain incurable, despite numerous research studies and the clinical need for effective treatments. Neural engineering is a diverse biomedical field, that addresses these diseases using new approaches. Research in the field involves principally rodent models and biologically active, biodegradable hydrogels. Promising results have been reported in preclinical studies of CNS repair, demonstrating the great potential for the development of new treatments for the brain, spinal cord and peripheral nerve injury. Several obstacles stand in the way of clinical translation of neuroregeneration research. There seems to be a key gap in the translation of research from rodent models to human applications, namely non-human primate models, which constitute a critical bridging step. Applying injectable therapeutics and multimodal neuroimaging in stroke lesions using experimental rhesus monkey models is an avenue that a few research groups have begun to embark on. Understanding and assessing the changes that the injured brain or spinal cord undergoes after an intervention with biodegradable hydrogels in non-human primates seem to represent critical preclinical research steps. Existing innovative models in non-human primates allow us to evaluate the potential of neural engineering and injectable hydrogels. The results of these preliminary studies will pave the way for translating this research into much needed clinical therapeutic approaches. Cutting edge imaging technology using Connectome scanners represents a tremendous advancement, enabling the in vivo, detailed, high-resolution evaluation of these therapeutic interventions in experimental animals. Most importantly, they also allow quantifiable and clinically meaningful correlations with humans, increasing the translatability of these

  10. Tracking Alu evolution in New World primates

    Directory of Open Access Journals (Sweden)

    Batzer Mark A

    2005-10-01

    Full Text Available Abstract Background Alu elements are Short INterspersed Elements (SINEs in primate genomes that have proven useful as markers for studying genome evolution, population biology and phylogenetics. Most of these applications, however, have been limited to humans and their nearest relatives, chimpanzees. In an effort to expand our understanding of Alu sequence evolution and to increase the applicability of these markers to non-human primate biology, we have analyzed available Alu sequences for loci specific to platyrrhine (New World primates. Results Branching patterns along an Alu sequence phylogeny indicate three major classes of platyrrhine-specific Alu sequences. Sequence comparisons further reveal at least three New World monkey-specific subfamilies; AluTa7, AluTa10, and AluTa15. Two of these subfamilies appear to be derived from a gene conversion event that has produced a recently active fusion of AluSc- and AluSp-type elements. This is a novel mode of origin for new Alu subfamilies. Conclusion The use of Alu elements as genetic markers in studies of genome evolution, phylogenetics, and population biology has been very productive when applied to humans. The characterization of these three new Alu subfamilies not only increases our understanding of Alu sequence evolution in primates, but also opens the door to the application of these genetic markers outside the hominid lineage.

  11. Reproductive/developmental toxicity and immunotoxicity assessment in the nonhuman primate model

    International Nuclear Information System (INIS)

    Buse, Eberhard; Habermann, Gunnar; Osterburg, Ingrid; Korte, Rainhart; Weinbauer, Gerhard F.

    2003-01-01

    Nonhuman primates are being used increasingly as a non-rodent animal model during preclinical toxicology and safety assessment on the basis of proven similarity and comparability between nonhuman primates and humans. The validity of the nonhuman primate models applies to many aspects of toxicological testing and holds particularly true for the evaluation of reproductive toxicology and developmental toxicology. More recently, the advent of humanized antibodies and vaccines imposed further demand on nonhuman primate models since many immunotherapeutics do not interact with rodent receptors but frequently only cross-react with primate tissue. In this paper we discuss the suitability of primate models for reproductive, developmental and immunotoxicology testing, and present our initial data on the development of lymphatic organs and immune system in a nonhuman primate model

  12. 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.

  13. Brief oral stimulation, but especially oral fat exposure, elevates serum triglycerides in humans

    Science.gov (United States)

    Mattes, Richard D.

    2009-01-01

    Oral exposure to dietary fat results in an early initial spike, followed by a prolonged elevation, of serum triglycerides in humans. The physiological and pathophysiological implications remain unknown. This study sought to determine the incidence of the effect, the required fat exposure duration, and its reliability. Thirty-four healthy adults participated in four to six response-driven trials held at least a week apart. They reported to the laboratory after an overnight fast, a catheter was placed in an antecubital vein, and a blood sample was obtained. Participants then ingested 50 g of safflower oil in capsules with 500 ml of water within 15 min to mimic a high fat meal but without oral fat exposure. Blood was collected 0, 10, 20, 30, 40, 50, 60, 120, 240, 360, and 480 min after capsule ingestion with different forms (full fat, nonfat, none) and durations of oral fat exposures (10 s, 5 min, 20 min, and/or 2 h). A triglyceride response (increase of triglyceride >10 mg/dl within 30 min) was observed in 88.2%, 70.5%, and 50% of participants with full-fat, nonfat, and no oral exposure, respectively. Test-retest reliability was 75% with full-fat exposure but only 45.4% with nonfat exposure. Full-fat and nonfat exposures led to comparable significant elevations of triglyceride over no oral stimulation with 10-s exposures, but full fat led to a greater rise than nonfat with 20 min of exposure. These data indicate that nutritionally relevant oral fat exposures reliably elevate serum triglyceride concentrations in most people. PMID:19074638

  14. Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers

    International Nuclear Information System (INIS)

    Chen Yongxin; Guo Yingqiu; Ge Xijin; Itoh, Hirotaka; Watanabe, Akira; Fujiwara, Takeshi; Kodama, Tatsuhiko; Aburatani, Hiroyuki

    2006-01-01

    In this report, we describe the expression and function of human Sp5, a member of the Sp family of zinc finger transcription factors. Like other family members, the Sp5 protein contains a Cys2His2 zinc finger DNA binding domain at the C-terminus. Our experiments employing Gal4-Sp5 fusion proteins reveal multiple transcriptional domains, including a N-terminal activity domain, an intrinsic repressive element, and a C-terminal synergistic domain. Elevated expression of Sp5 was noted in several human tumors including hepatocellular carcinoma, gastric cancer, and colon cancer. To study the effects of the Sp5 protein on growth properties of human cancer cells and facilitate the identification of its downstream genes, we combined an inducible gene expression system with microarray analysis to screen for its transcriptional targets. Transfer of Sp5 into MCF-7 cells that expressed no detectable endogenous Sp5 protein elicited significant growth promotion activity. Several of the constitutively deregulated genes have been associated with tumorigenesis (CDC25C, CEACAM6, TMPRSS2, XBP1, MYBL1, ABHD2, and CXCL12) and Wnt/β-Catenin signaling pathways (BAMBI, SIX1, IGFBP5, AES, and p21 WAF1 ). This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against human cancers

  15. Recent advances in primate nutritional ecology.

    Science.gov (United States)

    Righini, Nicoletta

    2017-04-01

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

  16. An elevated plus-maze in mixed reality for studying human anxiety-related behavior.

    Science.gov (United States)

    Biedermann, Sarah V; Biedermann, Daniel G; Wenzlaff, Frederike; Kurjak, Tim; Nouri, Sawis; Auer, Matthias K; Wiedemann, Klaus; Briken, Peer; Haaker, Jan; Lonsdorf, Tina B; Fuss, Johannes

    2017-12-21

    A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level. Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants' with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants' acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.

  17. Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates

    Directory of Open Access Journals (Sweden)

    Maria Eugenia Gallo Cantafio

    2016-01-01

    Full Text Available Locked nucleic acid (LNA oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i-miR-221 in plasma and urine, while a specific in situ hybridization assay for tissue uptake analysis was designed. Our analysis revealed short half-life, optimal tissue biovailability and minimal urine excretion of LNA-i-miR-221 in mice and monkeys. Up to 3 weeks, LNA-i-miR-221 was still detectable in mice vital organs and in xenografted tumors, together with p27 target upregulation. Importantly, no toxicity in the pilot monkey study was observed. Overall, our findings indicate the suitability of LNA-i-miR-221 for clinical use and we provide here pilot data for safety analysis and further development of LNA-miRNA-based therapeutics for human cancer.

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates

    International Nuclear Information System (INIS)

    Sekizawa, Shin-ichi; Joad, Jesse P.; Pinkerton, Kent E.; Bonham, Ann C.

    2010-01-01

    Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3 or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS

  20. Haloperidol-induced striatal Nur77 expression in a non-human primate model of tardive dyskinesia

    Science.gov (United States)

    Mahmoudi, Souha; Blanchet, Pierre J.; Lévesque, Daniel

    2015-01-01

    Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication arising in patients chronically exposed to antipsychotic drugs. As several modern (so-called atypical) antipsychotic drugs are common offenders, the widening clinical indications for prescription as well as exposure of vulnerable individuals, TD will remain a significant drug-induced unwanted side effect. In addition, the pathophysiology of TD remains elusive and therapeutics difficult. Based on rodent experiments, we have previously shown that the transcriptional factor Nur77 (also known as NGFI-B or Nr4a1) is induced in the striatum following antipsychotic drug exposure as part of a long-term neuroadaptive process. To confirm this, we exposed adult capuchin (Cebus apella) monkeys to prolonged treatments with haloperidol (median 18.5 months, N=11) or clozapine (median 6 months, N=6). Six untreated animals were used as controls. Six haloperidol-treated animals developed mild TD movements similar to those found in humans. No TD was observed in the clozapine group. Postmortem analysis of Nur77 expression measured by in situ hybridization revealed a stark contrast between the two drugs, as Nur77 mRNA levels in the caudate-putamen were strongly upregulated in animals exposed to haloperidol while spared following clozapine treatment. Interestingly, within the haloperidol-treated group, TD-free animals showed higher Nur77 expression in putamen subterritories compared to dyskinetic animals. This suggests that Nur77 expression might be associated with a reduced risk to TD in this experimental model and could provide a novel target for drug intervention. PMID:23551242

  1. Nonhuman Primate Studies to Advance Vision Science and Prevent Blindness.

    Science.gov (United States)

    Mustari, Michael J

    2017-12-01

    Most primate behavior is dependent on high acuity vision. Optimal visual performance in primates depends heavily upon frontally placed eyes, retinal specializations, and binocular vision. To see an object clearly its image must be placed on or near the fovea of each eye. The oculomotor system is responsible for maintaining precise eye alignment during fixation and generating eye movements to track moving targets. The visual system of nonhuman primates has a similar anatomical organization and functional capability to that of humans. This allows results obtained in nonhuman primates to be applied to humans. The visual and oculomotor systems of primates are immature at birth and sensitive to the quality of binocular visual and eye movement experience during the first months of life. Disruption of postnatal experience can lead to problems in eye alignment (strabismus), amblyopia, unsteady gaze (nystagmus), and defective eye movements. Recent studies in nonhuman primates have begun to discover the neural mechanisms associated with these conditions. In addition, genetic defects that target the retina can lead to blindness. A variety of approaches including gene therapy, stem cell treatment, neuroprosthetics, and optogenetics are currently being used to restore function associated with retinal diseases. Nonhuman primates often provide the best animal model for advancing fundamental knowledge and developing new treatments and cures for blinding diseases. © The Author(s) 2017. Published by Oxford University Press on behalf of the National Academy of Sciences. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Arnold Alma

    2004-10-01

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

  3. Resistance of human erythrocytes containing elevated levels of vitamin E to radiation-induced hemolysis

    International Nuclear Information System (INIS)

    Brown, M.A.

    1983-01-01

    Human erythrocytes were isolated from the blood of healthy donors and then incubated in the presence of suspensions of alpha-tocopherol for 30 min at 37 degrees C. Unabsorbed tocopherol was removed by centrifugation using several washes of isotonic phosphate-buffered saline. Washed erythrocytes were resuspended to 0.05%. Hct and exposed to hemolyzing doses of 60 Co gamma radiation, and hemolysis was monitored continuously by light scattering at 700 nm in a recording spectrophotometer. The extent of hemolysis with time was sigmoid and data analysis was carried out on the time taken for 50% hemolysis to occur (t50%). The vitamin E content of erythrocytes was significantly elevated by the incubation procedure and resulted in the cells exhibiting a significantly increased resistance to hemolysis as reflected by the extended t50% values. Oral supplementation of 500 IU of vitamin E per day to eight normal human subjects for a period of 16 days also resulted in their washed erythrocytes exhibiting a significant increase in resistance to radiation-induced hemolysis. When comparing vitamin E incubated cells with control cells, both the dose-reducing factor (DRF) and the time for 50% hemolysis quotient (Qt50%) were observed to increase with increasing radiation dose

  4. Induced Pluripotent Stem Cells from Nonhuman Primates.

    Science.gov (United States)

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

    2016-01-01

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

  5. Divergent lactate dehydrogenase isoenzyme profile in cellular compartments of primate forebrain structures.

    Science.gov (United States)

    Duka, Tetyana; Collins, Zachary; Anderson, Sarah M; Raghanti, Mary Ann; Ely, John J; Hof, Patrick R; Wildman, Derek E; Goodman, Morris; Grossman, Lawrence I; Sherwood, Chet C

    2017-07-01

    The compartmentalization and association of lactate dehydrogenase (LDH) with specific cellular structures (e.g., synaptosomal, sarcoplasmic or mitochondrial) may play an important role in brain energy metabolism. Our previous research revealed that LDH in the synaptosomal fraction shifts toward the aerobic isoforms (LDH-B) among the large-brained haplorhine primates compared to strepsirrhines. Here, we further analyzed the subcellular localization of LDH in primate forebrain structures using quantitative Western blotting and ELISA. We show that, in cytosolic and mitochondrial subfractions, LDH-B expression level was relatively elevated and LDH-A declined in haplorhines compared to strepsirrhines. LDH-B expression in mitochondrial fractions of the neocortex was preferentially increased, showing a particularly significant rise in the ratio of LDH-B to LDH-A in chimpanzees and humans. We also found a significant correlation between the protein levels of LDH-B in mitochondrial fractions from haplorhine neocortex and the synaptosomal LDH-B that suggests LDH isoforms shift from a predominance of A-subunits toward B-subunits as part of a system that spatially buffers dynamic energy requirements of brain cells. Our results indicate that there is differential subcellular compartmentalization of LDH isoenzymes that evolved among different primate lineages to meet the energy requirements in neocortical and striatal cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Antigenic relatedness of primate procollagens as determined by a competitive radioimmunoassay

    International Nuclear Information System (INIS)

    Taubman, M.B.; Goldberg, B.

    1978-01-01

    A radioimmunoassay specific for the nonhelical carboxy terminal portion of human type I procollagen was used to study the antigenic relatedness of primate procollagens. The assay identified reactive antigen in primate sera and in the media of primate fibroblast cultures. The displacement curves generated in the assay indicated that human and ape type I procollagens have antigenically identical carboxy terminal determinants which are partially cross-reactive with those from Old and New World monkeys. (author)

  7. Mycobacterium leprae genomes from naturally infected nonhuman primates.

    Science.gov (United States)

    Honap, Tanvi P; Pfister, Luz-Andrea; Housman, Genevieve; Mills, Sarah; Tarara, Ross P; Suzuki, Koichi; Cuozzo, Frank P; Sauther, Michelle L; Rosenberg, Michael S; Stone, Anne C

    2018-01-01

    Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild.

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

    Directory of Open Access Journals (Sweden)

    Anisur Rahman

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

  9. 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.

  10. Nonhuman primate models of focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2017-01-01

    Full Text Available Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

  11. GABA-mediated synchronization in the human neocortex: elevations in extracellular potassium and presynaptic mechanisms.

    Science.gov (United States)

    Louvel, J; Papatheodoropoulos, C; Siniscalchi, A; Kurcewicz, I; Pumain, R; Devaux, B; Turak, B; Esposito, V; Villemeure, J G; Avoli, M

    2001-01-01

    Field potential and extracellular [K(+)] ([K(+)](o)) recordings were made in the human neocortex in an in vitro slice preparation to study the synchronous activity that occurs in the presence of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists. Under these experimental conditions, negative or negative-positive field potentials accompanied by rises in [K(+)](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontaneously at intervals of 3-27 s. Both field potentials and [K(+)](o) elevations were largest at approximately 1000 microm from the pia. Similar events were induced by neocortical electrical stimuli. Application of medium containing low [Ca(2+)]/high [Mg(2+)] (n=3 slices), antagonism of the GABA(A) receptor (n=7) or mu-opioid receptor activation (n=4) abolished these events. Hence, they represented network, GABA-mediated potentials mainly reflecting the activation of type A receptors following GABA release from interneurons. The GABA(B) receptor agonist baclofen (10-100 microM, n=11) reduced and abolished the GABA-mediated potentials (ID(50)=18 microM). Baclofen effects were antagonized by the GABA(B) receptor antagonist CGP 35348 (0.1-1 mM, n=6; ID(50)=0.19 mM). CGP 38345 application to control medium increased the amplitude of the GABA-mediated potentials and the concomitant [K(+)](o) rises without modifying their rate of occurrence. The GABA-mediated potentials were not influenced by the broad-spectrum metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (100 microM, n=10), but decreased in rate with the group I receptor agonist (S)-3,5-dihydroxyphenylglycine (10-100 microM, n=9). Our data indicate that human neocortical networks challenged with 4-aminopyridine generate glutamatergic-independent, GABA-mediated potentials that are modulated by mu-opioid and GABA(B) receptors presumably located on interneuron terminals. These events are associated with [K(+)](o) elevations that may

  12. Distribution of the potto Perodictus potto (Primates: Lorisidae) in ...

    African Journals Online (AJOL)

    Journal of East African Natural History ... This paper (1) examines the Eastern Rift Valley as a major barrier to primate distribution in eastern Africa, (2) reviews the taxonomy of P. potto, (3) describes the distribution of the eastern potto P.p. ibeanus, (4) summarizes what is known about the body size, abundance, elevation ...

  13. Precursors to language: Social cognition and pragmatic inference in primates.

    Science.gov (United States)

    Seyfarth, Robert M; Cheney, Dorothy L

    2017-02-01

    Despite their differences, human language and the vocal communication of nonhuman primates share many features. Both constitute forms of coordinated activity, rely on many shared neural mechanisms, and involve discrete, combinatorial cognition that includes rich pragmatic inference. These common features suggest that during evolution the ancestors of all modern primates faced similar social problems and responded with similar systems of communication and cognition. When language later evolved from this common foundation, many of its distinctive features were already present.

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

    Science.gov (United States)

    Druelle, François; Aerts, Peter; Berillon, Gilles

    2016-11-01

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

  15. Further evidence for elevated human minisatellite mutation rate in Belarus eight years after the Chernobyl accident

    International Nuclear Information System (INIS)

    Dubrova, Yuri E.; Buard, Jerome; Jeffreys, Alec J.; Nesterov, Valeri N.; Krouchinsky, Nicolay G.; Ostapenko, Vladislav A.; Vergnaud, Gilles; Giraudeau, Fabienne

    1997-01-01

    Analysis of germline mutation rate at human minisatellites among children born in areas of the Mogilev district of Belarus heavily polluted after the Chernobyl accident has been extended, both by recruiting more families from the affected region and by using five additional minisatellite probes, including multi-locus probe 33.6 and four hypervariable single-locus probes. These additional data confirmed a twofold higher mutation rate in exposed families compared with non-irradiated families from the United Kingdom. An elevated rate was seen at all three independent sets of minisatellites (detected separately by multi-locus probes 33.15, 33.6 and six single-locus probes), indicating a generalised increase in minisatellite germline mutation rate in the Belarus families. Within the Belarus cohort, mutation rate was significantly greater in families with higher parental radiation dose estimated for chronic external and internal exposure to caesium-137, consistent with radiation induction of germline mutation. The spectra of mutation seen in the unexposed and exposed families were indistinguishable, suggesting that increased mutation observed over multiple loci arises indirectly by some mechanism that enhances spontaneous minisatellite mutation

  16. (±)-2-Chloropropionic acid elevates reactive oxygen species formation in human neutrophil granulocytes

    International Nuclear Information System (INIS)

    Aam, B.B.; Fonnum, F.

    2006-01-01

    (±)-2-Chloropropionic acid (2-CPA) is a neurotoxic compound which kills cerebellar granule cells in vivo, and makes cerebellar granule cells in vitro produce reactive oxygen species (ROS). We have studied the effect of 2-CPA on ROS formation in human neutrophil granulocytes in vitro. We found an increased formation of ROS after 2-CPA exposure using three different methods; the fluorescent probe DCFH-DA and the chemiluminescent probes lucigenin and luminol. Four different inhibitors of ROS formation were tested on the cells in combination with 2-CPA to characterize the signalling pathways. The spin-trap s-PBN, the ERK1/2 inhibitor U0126 and the antioxidant Vitamin E inhibited the 2-CPA-induced ROS formation completely, while the mitochondrial transition permeability pore blocker cyclosporine A inhibited the ROS formation partly. We also found that 2-CPA induced an increased nitric oxide production in the cells by using the Griess reagent. The level of reduced glutathione, measured with the DTNB assay, was decreased after exposure to high concentrations of 2-CPA. Western blotting analysis showed that 2-CPA exposure led to an elevated phosphorylation of ERK MAP kinase. This phosphorylation was inhibited by U0126. Based on these experiments it seems like the mechanisms for 2-CPA induced toxicity involves ROS formation and is similar in neutrophil granulocytes as earlier shown in cerebellar granule cells. This also implies that 2-CPA may be immunotoxic

  17. Nonhuman primate dermatology: a literature review

    Science.gov (United States)

    Bernstein, Joseph A.; Didier, Peter J.

    2015-01-01

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

  18. Cross-validation of commercial enzyme-linked immunosorbent assay and radioimmunoassay for porcine C-peptide concentration measurements in non-human primate serum.

    Science.gov (United States)

    Gresch, Sarah C; Mutch, Lucas A; Janecek, Jody L; Hegstad-Davies, Rebecca L; Graham, Melanie L

    2017-09-01

    C-peptide concentration is widely used as a marker of insulin secretion and is especially relevant in evaluating islet graft function following transplantation, because its measurement is not confounded by the presence of exogenous insulin. To address the shortage of human islet donors, the use of porcine islets has been proposed as a possible solution and the stringent pig-to-non-human primate (NHP) model is often the most relevant for pre-clinical evaluation of the potential for diabetes reversal resulting from an islet xenograft. The Millipore radioimmunoassay (RIA) was exclusively used to measure porcine C-peptide (PCP) until 2013 when the assay was discontinued and subsequently a commercially available enzyme-linked immunosorbent assay (ELISA) from Mercodia has been widely adopted. Both assays have been used in pre-clinical trials evaluating the therapeutic potential of xenograft products in reversing diabetes in the pig-to-NHP model, to interpret data in a comparable way it may be useful to perform a harmonization of C-peptide measurements. We performed a method comparison by determining the PCP concentration in 620 serum samples collected from 20 diabetic cynomolgus macaques transplanted with adult porcine islets. All analyses were performed according to manufacturer instructions. With both assays, we demonstrated an acceptable detection limit, precision, and recovery. Linearity of the ELISA met acceptance criteria at all concentrations tested while linearity of the RIA only met acceptance criteria at five of the eight concentrations tested. The RIA had a detection limit of 0.16 ng/mL, and recovery ranged from 82% to 96% and met linearity acceptance criteria at 0.35 ng/mL and from 0.78 to 2.33 ng/mL. The ELISA had a detection limit of 0.03 ng/mL, and recovery ranged from 81% to 115% and met linearity acceptance criteria from 0.08 to 0.85 ng/mL. Both assays had intra-assay precision assay precision ELISA demonstrated a significant correlation with RIA (R

  19. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons

    DEFF Research Database (Denmark)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without ...

  20. Elevated temperature triggers human respiratory syncytial virus F protein six-helix bundle formation

    International Nuclear Information System (INIS)

    Yunus, Abdul S.; Jackson, Trent P.; Crisafi, Katherine; Burimski, Irina; Kilgore, Nicole R.; Zoumplis, Dorian; Allaway, Graham P.; Wild, Carl T.; Salzwedel, Karl

    2010-01-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in infants, immunocompromised patients, and the elderly. The RSV fusion (F) protein mediates fusion of the viral envelope with the target cell membrane during virus entry and is a primary target for antiviral drug and vaccine development. The F protein contains two heptad repeat regions, HR1 and HR2. Peptides corresponding to these regions form a six-helix bundle structure that is thought to play a critical role in membrane fusion. However, characterization of six-helix bundle formation in native RSV F protein has been hindered by the fact that a trigger for F protein conformational change has yet to be identified. Here we demonstrate that RSV F protein on the surface of infected cells undergoes a conformational change following exposure to elevated temperature, resulting in the formation of the six-helix bundle structure. We first generated and characterized six-helix bundle-specific antibodies raised against recombinant peptides modeling the RSV F protein six-helix bundle structure. We then used these antibodies as probes to monitor RSV F protein six-helix bundle formation in response to a diverse array of potential triggers of conformational changes. We found that exposure of 'membrane-anchored' RSV F protein to elevated temperature (45-55 deg. C) was sufficient to trigger six-helix bundle formation. Antibody binding to the six-helix bundle conformation was detected by both flow cytometry and cell-surface immunoprecipitation of the RSV F protein. None of the other treatments, including interaction with a number of potential receptors, resulted in significant binding by six-helix bundle-specific antibodies. We conclude that native, untriggered RSV F protein exists in a metastable state that can be converted in vitro to the more stable, fusogenic six-helix bundle conformation by an increase in thermal energy. These findings help to better define the mechanism of

  1. Primate Torpor: Regulation of Stress-activated Protein Kinases During Daily Torpor in the Gray Mouse Lemur, Microcebus murinus

    Directory of Open Access Journals (Sweden)

    Kyle K. Biggar

    2015-04-01

    Full Text Available Very few selected species of primates are known to be capable of entering torpor. This exciting discovery means that the ability to enter a natural state of dormancy is an ancestral trait among primates and, in phylogenetic terms, is very close to the human lineage. To explore the regulatory mechanisms that underlie primate torpor, we analyzed signal transduction cascades to discover those involved in coordinating tissue responses during torpor. The responses of mitogen-activated protein kinase (MAPK family members to primate torpor were compared in six organs of control (aroused versus torpid gray mouse lemurs, Microcebus murinus. The proteins examined include extracellular signal-regulated kinases (ERKs, c-jun NH2-terminal kinases (JNKs, MAPK kinase (MEK, and p38, in addition to stress-related proteins p53 and heat shock protein 27 (HSP27. The activation of specific MAPK signal transduction pathways may provide a mechanism to regulate the expression of torpor-responsive genes or the regulation of selected downstream cellular processes. In response to torpor, each MAPK subfamily responded differently during torpor and each showed organ-specific patterns of response. For example, skeletal muscle displayed elevated relative phosphorylation of ERK1/2 during torpor. Interestingly, adipose tissues showed the highest degree of MAPK activation. Brown adipose tissue displayed an activation of ERK1/2 and p38, whereas white adipose tissue showed activation of ERK1/2, p38, MEK, and JNK during torpor. Importantly, both adipose tissues possess specialized functions that are critical for torpor, with brown adipose required for non-shivering thermogenesis and white adipose utilized as the primary source of lipid fuel for torpor. Overall, these data indicate crucial roles of MAPKs in the regulation of primate organs during torpor.

  2. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.

    Science.gov (United States)

    Wang, Jichang; Xie, Gangcai; Singh, Manvendra; Ghanbarian, Avazeh T; Raskó, Tamás; Szvetnik, Attila; Cai, Huiqiang; Besser, Daniel; Prigione, Alessandro; Fuchs, Nina V; Schumann, Gerald G; Chen, Wei; Lorincz, Matthew C; Ivics, Zoltán; Hurst, Laurence D; Izsvák, Zsuzsanna

    2014-12-18

    Naive embryonic stem cells hold great promise for research and therapeutics as they have broad and robust developmental potential. While such cells are readily derived from mouse blastocysts it has not been possible to isolate human equivalents easily, although human naive-like cells have been artificially generated (rather than extracted) by coercion of human primed embryonic stem cells by modifying culture conditions or through transgenic modification. Here we show that a sub-population within cultures of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) manifests key properties of naive state cells. These naive-like cells can be genetically tagged, and are associated with elevated transcription of HERVH, a primate-specific endogenous retrovirus. HERVH elements provide functional binding sites for a combination of naive pluripotency transcription factors, including LBP9, recently recognized as relevant to naivety in mice. LBP9-HERVH drives hESC-specific alternative and chimaeric transcripts, including pluripotency-modulating long non-coding RNAs. Disruption of LBP9, HERVH and HERVH-derived transcripts compromises self-renewal. These observations define HERVH expression as a hallmark of naive-like hESCs, and establish novel primate-specific transcriptional circuitry regulating pluripotency.

  3. Primate Anatomy, Kinematics, and Principles for Humanoid Design

    Science.gov (United States)

    Ambrose, Robert O.; Ambrose, Catherine G.

    2004-01-01

    The primate order of animals is investigated for clues in the design of Humanoid Robots. The pursuit is directed with a theory that kinematics, musculature, perception, and cognition can be optimized for specific tasks by varying the proportions of limbs, and in particular, the points of branching in kinematic trees such as the primate skeleton. Called the Bifurcated Chain Hypothesis, the theory is that the branching proportions found in humans may be superior to other animals and primates for the tasks of dexterous manipulation and other human specialties. The primate taxa are defined, contemporary primate evolution hypotheses are critiqued, and variations within the order are noted. The kinematic branching points of the torso, limbs and fingers are studied for differences in proportions across the order, and associated with family and genus capabilities and behaviors. The human configuration of a long waist, long neck, and short arms is graded using a kinematic workspace analysis and a set of design axioms for mobile manipulation robots. It scores well. The re emergence of the human waist, seen in early Prosimians and Monkeys for arboreal balance, but lost in the terrestrial Pongidae, is postulated as benefiting human dexterity. The human combination of an articulated waist and neck will be shown to enable the use of smaller arms, achieving greater regions of workspace dexterity than the larger limbs of Gorillas and other Hominoidea.

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

    Science.gov (United States)

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

    2014-02-13

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

  5. The behavioral genetics of nonhuman primates: Status and prospects.

    Science.gov (United States)

    Rogers, Jeffrey

    2018-01-01

    The complexity and diversity of primate behavior have long attracted the attention of ethologists, psychologists, behavioral ecologists, and neuroscientists. Recent studies have advanced our understanding of the nature of genetic influences on differences in behavior among individuals within species. A number of analyses have focused on the genetic analysis of behavioral reactions to specific experimental tests, providing estimates of the degree of genetic control over reactivity, and beginning to identify the genes involved. Substantial progress is also being made in identifying genetic factors that influence the structure and function of the primate brain. Most of the published studies on these topics have examined either cercopithecines or chimpanzees, though a few studies have addressed these questions in other primate species. One potentially important line of research is beginning to identify the epigenetic processes that influence primate behavior, thus revealing specific cellular and molecular mechanisms by which environmental experiences can influence gene expression or gene function relevant to behavior. This review summarizes many of these studies of non-human primate behavioral genetics. The primary focus is on analyses that address the nature of the genes and genetic processes that affect differences in behavior among individuals within non-human primate species. Analyses of between species differences and potential avenues for future research are also discussed. © 2018 American Association of Physical Anthropologists.

  6. Primates and the Evolution of Long-Slow Life Histories

    Science.gov (United States)

    Jones, James Holland

    2011-01-01

    Summary Primates are characterized by relatively late ages at first reproduction, long lives and low fertility. Together, these traits define a life-history of reduced reproductive effort. Understanding the optimal allocation of reproductive effort, and specifically reduced reproductive effort, has been one of the key problems motivating the development of life history theory. Because of their unusual constellation of life-history traits, primates play an important role in the continued development of life history theory. In this review, I present the evidence for the reduced reproductive effort life histories of primates and discuss the ways that such life-history tactics are understood in contemporary theory. Such tactics are particularly consistent with the predictions of stochastic demographic models, suggesting a key role for environmental variability in the evolution of primate life histories. The tendency for primates to specialize in high-quality, high-variability food items may make them particularly susceptible to environmental variability and explain their low reproductive-effort tactics. I discuss recent applications of life history theory to human evolution and emphasize the continuity between models used to explain peculiarities of human reproduction and senescence with the long, slow life histories of primates more generally. PMID:21959161

  7. 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.

    Science.gov (United States)

    Carter, Anthony M

    2011-04-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human 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. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

  8. Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

    Science.gov (United States)

    Saunders, Kevin O; Santra, Sampa; Parks, Robert; Yates, Nicole L; Sutherland, Laura L; Scearce, Richard M; Balachandran, Harikrishnan; Bradley, Todd; Goodman, Derrick; Eaton, Amanda; Stanfield-Oakley, Sherry A; Tartaglia, James; Phogat, Sanjay; Pantaleo, Giuseppe; Esteban, Mariano; Gomez, Carmen E; Perdiguero, Beatriz; Jacobs, Bertram; Kibler, Karen; Korber, Bette; Montefiori, David C; Ferrari, Guido; Vandergrift, Nathan; Liao, Hua-Xin; Tomaras, Georgia D; Haynes, Barton F

    2018-04-15

    A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge. IMPORTANCE The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model. Copyright © 2018 American Society for Microbiology.

  9. Canine distemper virus isolated from a monkey efficiently replicates on Vero cells expressing non-human primate SLAM receptors but not human SLAM receptor.

    Science.gov (United States)

    Feng, Na; Liu, Yuxiu; Wang, Jianzhong; Xu, Weiwei; Li, Tiansong; Wang, Tiecheng; Wang, Lei; Yu, Yicong; Wang, Hualei; Zhao, Yongkun; Yang, Songtao; Gao, Yuwei; Hu, Guixue; Xia, Xianzhu

    2016-08-02

    In 2008, an outbreak of canine distemper virus (CDV) infection in monkeys was reported in China. We isolated CDV strain (subsequently named Monkey-BJ01-DV) from lung tissue obtained from a rhesus monkey that died in this outbreak. We evaluated the ability of this virus on Vero cells expressing SLAM receptors from dog, monkey and human origin, and analyzed the H gene of Monkey-BJ01-DV with other strains. The Monkey-BJ01-DV isolate replicated to the highest titer on Vero cells expressing dog-origin SLAM (10(5.2±0.2) TCID50/ml) and monkey-origin SLAM (10(5.4±0.1) TCID50/ml), but achieved markedly lower titers on human-origin SLAM cells (10(3.3±0.3) TCID50/ml). Phylogenetic analysis of the full-length H gene showed that Monkey-BJ01-DV was highly related to other CDV strains obtained during recent CDV epidemics among species of the Canidae family in China, and these Monkey strains CDV (Monkey-BJ01-DV, CYN07-dV, Monkey-KM-01) possessed a number of amino acid specific substitutions (E276V, Q392R, D435Y and I542F) compared to the H protein of CDV epidemic in other animals at the same period. Our results suggested that the monkey origin-CDV-H protein could possess specific substitutions to adapt to the new host. Monkey-BJ01-DV can efficiently use monkey- and dog-origin SLAM to infect and replicate in host cells, but further adaptation may be required for efficient replication in host cells expressing the human SLAM receptor.

  10. Dietary quality and encephalization in platyrrhine primates

    Science.gov (United States)

    Allen, Kari L.; Kay, Richard F.

    2012-01-01

    The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The ‘expensive-tissue hypothesis’ (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans. PMID:21831898

  11. Dietary quality and encephalization in platyrrhine primates.

    Science.gov (United States)

    Allen, Kari L; Kay, Richard F

    2012-02-22

    The high energetic costs of building and maintaining large brains are thought to constrain encephalization. The 'expensive-tissue hypothesis' (ETH) proposes that primates (especially humans) overcame this constraint through reduction of another metabolically expensive tissue, the gastrointestinal tract. Small guts characterize animals specializing on easily digestible diets. Thus, the hypothesis may be tested via the relationship between brain size and diet quality. Platyrrhine primates present an interesting test case, as they are more variably encephalized than other extant primate clades (excluding Hominoidea). We find a high degree of phylogenetic signal in the data for diet quality, endocranial volume and body size. Controlling for phylogenetic effects, we find no significant correlation between relative diet quality and relative endocranial volume. Thus, diet quality fails to account for differences in platyrrhine encephalization. One taxon, in particular, Brachyteles, violates predictions made by ETH in having a large brain and low-quality diet. Dietary reconstructions of stem platyrrhines further indicate that a relatively high-quality diet was probably in place prior to increases in encephalization. Therefore, it is unlikely that a shift in diet quality was a primary constraint release for encephalization in platyrrhines and, by extrapolation, humans.

  12. 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. © 2010 Wiley-Liss, Inc.

  13. Elevating your elevator talk

    Science.gov (United States)

    An important and often overlooked item that every early career researcher needs to do is compose an elevator talk. The elevator talk, named because the talk should not last longer than an average elevator ride (30 to 60 seconds), is an effective method to present your research and yourself in a clea...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Intraarterial reteplase and intravenous abciximab for treatment of acute ischemic stroke. A preliminary feasibility and safety study in a non-human primate model

    International Nuclear Information System (INIS)

    Qureshi, Adnan I.; Suri, M. Fareed K.; Ali, Zulfiqar; Ringer, Andrew J.; Boulos, Alan S.; Guterman, Lee R.; Hopkins, L. Nelson; Nakada, Marian T.; Alberico, Ronald A.; Martin, Lisa B.E.

    2005-01-01

    We performed a preliminary feasibility and safety study using intravenous (IV) administration of a platelet glycoprotein IIb/IIIa inhibitor (abciximab) in conjunction with intraarterial (IA) administration of a thrombolytic agent (reteplase) in a primate model of intracranial thrombosis. We introduced thrombus through superselective catheterization of the intracranial segment of the internal carotid artery in 16 primates. The animals were randomly assigned to receive IA reteplase and IV abciximab (n =4), IA reteplase and IV placebo (n =4), IA placebo and IV abciximab (n =4) or IA and IV placebo (n =4). Recanalization was assessed by serial angiography during the 6-h period after initiation of treatment. Postmortem magnetic resonance (MR) imaging was performed to determine the presence of cerebral infarction or intracranial hemorrhage. Partial or complete recanalization at 6 h after initiation of treatment (decrease of two or more points in pre-treatment angiographic occlusion grade) was observed in two animals treated with IA reteplase and IV abciximab, three animals treated with IA reteplase alone and one animal treated with IV abciximab alone. No improvement in perfusion was observed in animals that received IV and IA placebo. Cerebral infarction was demonstrated on postmortem MR imaging in three animals that received IA and IV placebo and in one animal each from the groups that received IA reteplase and IV abciximab or IV abciximab alone. One animal that received IV abciximab alone had a small intracerebral hemorrhage on MR imaging. (orig.)

  16. Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

    Science.gov (United States)

    Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

    2017-05-01

    Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. 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

    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....... Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth...... restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders....

  18. Functional comparison of innate immune signaling pathways in primates.

    Directory of Open Access Journals (Sweden)

    Luis B Barreiro

    2010-12-01

    Full Text Available Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

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

    Directory of Open Access Journals (Sweden)

    Hayes Eric S

    2004-06-01

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

  20. 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.

  1. Primates on display: Potential disease consequences beyond bushmeat.

    Science.gov (United States)

    Muehlenbein, Michael P

    2017-01-01

    Human interactions with nonhuman primates vary tremendously, from daily cultural engagements and food commodities, to pet ownership and tourist encounters. These interactions provide opportunities for the exchange of pathogenic organisms (both zoonoses and anthroponoses). As exposures are not limited to areas where bushmeat usage continues to be a major problem, we must work to understand better our motivations for engaging in activities like owning primates as pets and having direct physical contact with wild primates within the context of nature-based tourism. These topics, and the theoretical potential for pathogen transmission, are reviewed in the present manuscript. This is followed by a case study utilizing 3845 survey responses collected from four international locations known for primate-based tourism, with results indicating that while a majority of people understand that they can give/get diseases to/from wild primates, a surprising percentage would still touch or feed these animals if given the opportunity. Many people still choose to touch and/or own primates, as their drive to bond with animals outweighs some basic health behaviors. Desires to tame, control, or otherwise establish emotional connections with other species, combined with the central role of touch for exploring our environment, necessitate the development of better communication and educational campaigns to minimize risks of emerging infectious diseases. © 2017 American Association of Physical Anthropologists.

  2. Immune Responses in the Central Nervous System Are Anatomically Segregated in a Non-Human Primate Model of Human Immunodeficiency Virus Infection

    Directory of Open Access Journals (Sweden)

    Barbara Tavano

    2017-03-01

    Full Text Available The human immunodeficiency virus (HIV accesses the central nervous system (CNS early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing. These immunologic alterations were not accompanied by differences in SIV transcriptional activity within the tissue. Altered expression of genes associated with neurotoxicity was observed in both midbrain and frontal lobe. The segregation of inflammatory responses to specific regions of the CNS may both account for HIV-associated neurological symptoms and constitute a critical hurdle for HIV eradication by shielding the CNS viral reservoir from antiviral immunity.

  3. Social learning of vocal structure in a nonhuman primate?

    Directory of Open Access Journals (Sweden)

    Lemasson Alban

    2011-12-01

    Full Text Available Abstract Background Non-human primate communication is thought to be fundamentally different from human speech, mainly due to vast differences in vocal control. The lack of these abilities in non-human primates is especially striking if compared to some marine mammals and bird species, which has generated somewhat of an evolutionary conundrum. What are the biological roots and underlying evolutionary pressures of the human ability to voluntarily control sound production and learn the vocal utterances of others? One hypothesis is that this capacity has evolved gradually in humans from an ancestral stage that resembled the vocal behavior of modern primates. Support for this has come from studies that have documented limited vocal flexibility and convergence in different primate species, typically in calls used during social interactions. The mechanisms underlying these patterns, however, are currently unknown. Specifically, it has been difficult to rule out explanations based on genetic relatedness, suggesting that such vocal flexibility may not be the result of social learning. Results To address this point, we compared the degree of acoustic similarity of contact calls in free-ranging Campbell's monkeys as a function of their social bonds and genetic relatedness. We calculated three different indices to compare the similarities between the calls' frequency contours, the duration of grooming interactions and the microsatellite-based genetic relatedness between partners. We found a significantly positive relation between bond strength and acoustic similarity that was independent of genetic relatedness. Conclusion Genetic factors determine the general species-specific call repertoire of a primate species, while social factors can influence the fine structure of some the call types. The finding is in line with the more general hypothesis that human speech has evolved gradually from earlier primate-like vocal communication.

  4. Pervasive Adaptive Evolution in Primate Seminal Proteins.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Seminal fluid proteins show striking effects on reproduction, involving manipulation of female behavior and physiology, mechanisms of sperm competition, and pathogen defense. Strong adaptive pressures are expected for such manifestations of sexual selection and host defense, but the extent of positive selection in seminal fluid proteins from divergent taxa is unknown. We identified adaptive evolution in primate seminal proteins using genomic resources in a tissue-specific study. We found extensive signatures of positive selection when comparing 161 human seminal fluid proteins and 2,858 prostate-expressed genes to those in chimpanzee. Seven of eight outstanding genes yielded statistically significant evidence of positive selection when analyzed in divergent primates. Functional clues were gained through divergent analysis, including several cases of species-specific loss of function in copulatory plug genes, and statistically significant spatial clustering of positively selected sites near the active site of kallikrein 2. This study reveals previously unidentified positive selection in seven primate seminal proteins, and when considered with findings in Drosophila, indicates that extensive positive selection is found in seminal fluid across divergent taxonomic groups.

  5. 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. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  6. ATP and phosphocreatine utilization in single human muscle fibres during the development of maximal power output at elevated muscle temperatures.

    Science.gov (United States)

    Gray, Stuart R; Söderlund, Karin; Ferguson, Richard A

    2008-05-01

    In this study, we examined the effect of muscle temperature (Tm) on adenosine triphosphate (ATP) and phosphocreatine utilization in single muscle fibres during the development of maximal power output in humans. Six male participants performed a 6-s maximal sprint on a friction-braked cycle ergometer under both normal (Tm = 34.3 degrees C, s = 0.6) and elevated (T(m) = 37.3 degrees C, s = 0.2) muscle temperature conditions. During the elevated condition, muscle temperature of the legs was raised, passively, by hot water immersion followed by wrapping in electrically heated blankets. Muscle biopsies were taken from the vastus lateralis before and immediately after exercise. Freeze-dried single fibres were dissected, characterized according to myosin heavy chain composition, and analysed for ATP and phosphocreatine content. Single fibres were classified as: type I, IIA, IIAX25 (1 - 25% IIX isoform), IIAX50 (26 - 50% IIX), IIAX75 (51 - 75% IIX), or IIAX100 (76 - 100% IIX). Maximal power output and pedal rate were both greater (P < 0.05) during the elevated condition by 258 W (s = 110) and 22 rev . min(-1) (s = 6), respectively. In both conditions, phosphocreatine content decreased significantly in all fibre types, with a greater decrease during the elevated condition in type IIA fibres (P < 0.01). Adenosine triphosphate content was also reduced to a greater (P < 0.01) extent in type IIA fibres during the elevated condition. The results of the present study indicate that after passive elevation of muscle temperature, there was a greater decrease in ATP and phosphocreatine content in type IIA fibres than in the normal trial, which contributed to the higher maximal power output.

  7. Threatened species richness along a Himalayan elevational gradient: quantifying the influences of human population density, range size, and geometric constraints.

    Science.gov (United States)

    Paudel, Prakash Kumar; Sipos, Jan; Brodie, Jedediah F

    2018-02-07

    A crucial step in conserving biodiversity is to identify the distributions of threatened species and the factors associated with species threat status. In the biodiversity hotspot of the Himalaya, very little is known about which locations harbour the highest diversity of threatened species and whether diversity of such species is related to area, mid-domain effects (MDE), range size, or human density. In this study, we assessed the drivers of variation in richness of threatened birds, mammals, reptiles, actinopterygii, and amphibians along an elevational gradient in Nepal Himalaya. Although geometric constraints (MDE), species range size, and human population density were significantly related to threatened species richness, the interaction between range size and human population density was of greater importance. Threatened species richness was positively associated with human population density and negatively associated with range size. In areas with high richness of threatened species, species ranges tend to be small. The preponderance of species at risk of extinction at low elevations in the subtropical biodiversity hotspot could be due to the double impact of smaller range sizes and higher human density.

  8. Effect of land use dynamics on habitat of two sympatric primates in ...

    African Journals Online (AJOL)

    Competition between growing human population and burgeoning number of primates were investigated at the Boabeng-Fiema monkey sanctuary (BFMS) in Ghana, to determine the effect of habitat change on primates. Remote sensing data, primarily Landsat imagery, were used to analyse the land use cover changes that ...

  9. Acute moderate elevation of TNF-{alpha} does not affect systemic and skeletal muscle protein turnover in healthy humans

    DEFF Research Database (Denmark)

    Petersen, Anne Marie; Plomgaard, Peter; Fischer, Christian P

    2009-01-01

    -alpha infusion (rhTNF-alpha). We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibit synthesis. Subjects and Methods: Using a randomized controlled, crossover design post-absorptive healthy young males (n=8) were studied 2 hours under basal conditions followed by 4 hours infusion...... with the phenylalanine 3-compartment model showed similar muscle synthesis, breakdown and net muscle degradation after 2 hours basal and after 4 hours Control or rhTNF-alpha infusion. Conclusion: This study is the first to show in humans that TNF-alpha does not affect systemic and skeletal muscle protein turnover, when......Context: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha. Objective: In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover, via a 4 hours recombinant human TNF...

  10. Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

    International Nuclear Information System (INIS)

    Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.; Stuzman, R.E.

    1982-01-01

    Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadal function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men

  11. A small nonhuman primate model for filovirus-induced disease.

    Science.gov (United States)

    Carrion, Ricardo; Ro, Youngtae; Hoosien, Kareema; Ticer, Anysha; Brasky, Kathy; de la Garza, Melissa; Mansfield, Keith; Patterson, Jean L

    2011-11-25

    Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. On folivory, competition, and intelligence: generalisms, overgeneralizations, and models of primate evolution.

    Science.gov (United States)

    Sayers, Ken

    2013-04-01

    Considerations of primate behavioral evolution often proceed by assuming the ecological and competitive milieus of particular taxa via their relative exploitation of gross food types, such as fruits versus leaves. Although this "fruit/leaf dichotomy" has been repeatedly criticized, it continues to be implicitly invoked in discussions of primate socioecology and female social relationships and is explicitly invoked in models of brain evolution. An expanding literature suggests that such views have severely limited our knowledge of the social and ecological complexities of primate folivory. This paper examines the behavior of primate folivore-frugivores, with particular emphasis on gray langurs (traditionally, Semnopithecus entellus) within the broader context of evolutionary ecology. Although possessing morphological characteristics that have been associated with folivory and constrained activity patterns, gray langurs are known for remarkable plasticity in ecology and behavior. Their diets are generally quite broad and can be discussed in relation to Liem's Paradox, the odd coupling of anatomical feeding specializations with a generalist foraging strategy. Gray langurs, not coincidentally, inhabit arguably the widest range of habitats for a nonhuman primate, including high elevations in the Himalayas. They provide an excellent focal point for examining the assumptions and predictions of behavioral, socioecological, and cognitive evolutionary models. Contrary to the classical descriptions of the primate folivore, Himalayan and other gray langurs-and, in actuality, many leaf-eating primates-range widely, engage in resource competition (both of which have previously been noted for primate folivores), and solve ecological problems rivaling those of more frugivorous primates (which has rarely been argued for primate folivores). It is maintained that questions of primate folivore adaptation, temperate primate adaptation, and primate evolution more generally cannot be

  13. Elevational patterns of Polylepis tree height (Rosaceae in the high Andes of Peru: role of human impact and climatic conditions

    Directory of Open Access Journals (Sweden)

    Michael eKessler

    2014-05-01

    Full Text Available We studied tree height in stands of high-Andean Polylepis forests in two cordilleras near Cuzco (Peru with respect to variations in human impact and climatic conditions, and compared air and soil temperatures between qualitatively defined dry and humid slopes. We studied 46 forest plots of 100 m2 of five Polylepis species at 3560-4680 m. We measured diameter at breast height (dbh and tree height in the stands (1229 trees in total, as well as air and soil temperatures in a subset of plots. The data was analysed combining plots of given species from different sites at the same elevation (±100 m. There was no elevational decrease of mean maximum tree height across the entire data set. On humid slopes, tree height decreased continuously with elevation, whereas on dry slopes it peaked at middle elevations. With mean maximum tree heights of 9 m at 4530 m on the humid slopes and of 13 m at 4650 m on the dry slopes, we here document the tallest high-elevation forests found so far worldwide. These highest stands grow under cold mean growing season air temperatures (3.6 °C and 3.8 °C on humid vs. dry slopes and mean growing season soil temperatures (5.1 °C vs. 4.6 °C. Mean annual air and soil temperature both decreased with elevation. Dry slopes had higher mean and maximum growing season air temperatures than humid slopes. Mean annual soil temperatures did not significantly differ and mean annual air temperatures only slightly differed between slopes. However, maximum air temperatures differed on average by 6.6 K between dry and humid slopes. This suggests that the differences in tree height between the two slopes are most likely due to differences in solar radiation as reflected by maximum air temperatures. Our study furthermore provides evidence that alpine Polylepis treelines grow under lower temperature conditions than global high-elevation treelines on average, suggesting that Polylepis species may have evolved special physiological adaptations

  14. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  15. Firing probability and mean firing rates of human muscle vasoconstrictor neurones are elevated during chronic asphyxia

    DEFF Research Database (Denmark)

    Ashley, Cynthia; Burton, Danielle; Sverrisdottir, Yrsa B

    2010-01-01

    in the obstructive sleep apnoea syndrome (OSAS) is associated with an increase in firing probability and mean firing rate, and an increase in multiple within-burst firing. Here we characterize the firing properties of muscle vasoconstrictor neurones in patients with chronic obstructive pulmonary disease (COPD), who...... are chronically asphyxic. We tested the hypothesis that this elevated chemical drive would shift the firing pattern from that seen in healthy subjects to that seen in OSAS. The mean firing probability (52%) and mean firing rate (0.92 Hz) of 17 muscle vasoconstrictor neurones recorded in COPD were comparable...

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

    Directory of Open Access Journals (Sweden)

    Kouassi Roland Yao Wa

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. The human clone ST22 SCCmec IV methicillin-resistant Staphylococcus aureus isolated from swine herds and wild primates in Nepal: is man the common source?

    Science.gov (United States)

    Roberts, Marilyn C; Joshi, Prabhu Raj; Greninger, Alexander L; Melendez, Daira; Paudel, Saroj; Acharya, Mahesh; Bimali, Nabin Kishor; Koju, Narayan P; No, David; Chalise, Mukesh; Kyes, Randall C

    2018-05-01

    Swine nasal samples [n = 282] were collected from 12 randomly selected farms around Kathmandu, Nepal, from healthy animals. In addition, wild monkey (Macaca mulatta) saliva samples [n = 59] were collected near temples areas in Kathmandu using a non-invasive sampling technique. All samples were processed for MRSA using standardized selective media and conventional biochemical tests. MRSA verification was done and isolates characterized by SCCmec, multilocus sequence typing, whole genome sequencing [WGS] and antibiotic susceptibilities. Six (2.1%) swine MRSA were isolated from five of the different swine herds tested, five were ST22 type IV and one ST88 type V. Four (6.8%) macaques MRSA were isolated, with three ST22 SCCmec type IV and one ST239 type III. WGS sequencing showed that the eight ciprofloxacin resistant ST22 isolates carried gyrA mutation [S84L]. Six isolates carried the erm(C) genes, five isolates carried aacC-aphD genes and four isolates carried blaZ genes. The swine linezolid resistant ST22 did not carry any known acquired linezolid resistance genes but had a mutation in ribosomal protein L22 [A29V] and an insertion in L4 [68KG69], both previously associated with linezolid resistance. Multiple virulence factors were also identified. This is the first time MRSA ST22 SCCmec IV has been isolated from livestock or primates.

  19. Measurement of the Effect of Phenothiazine on the Manganese Concentration in the Basal Ganglia of Sub-Human Primates by Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bird, E. D.; Grant, L. G.; Ellis, W. H. [University of Florida, Gainesville, FL (United States)

    1967-10-15

    In man toxicity to manganese and phenothiazine drugs is manifested as dyskinesia. Cotzias and co-workers demonstrated that the phenothiazines form a semiquinone radical with manganese suggesting a common mechanism for production of Parkinsonism. Previous measurements of manganese have been made on whole brain. The very sensitive technique of activation analysis was used in the present study to measure manganese concentration in various nuclei of the basal ganglia. Phenothiazine was given to one group of Rhesus monkeys (Macaca mulatta) for one month. One group served as a control. After sacrifice the basal ganglia were dissected out with plastic knives, dried, and duplicate samples exposed to thermal neutrons at a flux of 1.35 x 10{sup 12} n/cm{sup 2}s. Manganese was separated radiochemical and counts under the manganese peak were compared to a standard handled identically. The results are presented. The manganese concentration was significantly increased in the putamen of primates receiving phenothiazine. There was no significant difference in the other nuclei examined. Phenothiazine is concentrated in basal ganglia. Dopamine is found in large quantities in caudate and putamen, and following phenothiazine therapy dopamine was found to be increased slightly. The associated increase of manganese and dopamine following phenothiazine provides some evidence that this drug causes profound biochemical alterations in the basal ganglia resulting in the various dyskinesias that are seen. (author)

  20. Elevated human chorionic gonadotropin levels in patients with chronic kidney disease: Case series and review of literature

    Directory of Open Access Journals (Sweden)

    S Soni

    2013-01-01

    Full Text Available Women are often subj