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Sample records for infected monkeys showed

  1. Plasmodium simium/Plasmodium vivax infections in southern brown howler monkeys from the Atlantic Forest

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    Daniela Camargos Costa

    2014-08-01

    Full Text Available Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4% and in wild Alouatta clamitans monkeys (n = 20, 35% from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.

  2. Experimental cross-species infection of common marmosets by titi monkey adenovirus.

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    Guixia Yu

    Full Text Available Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV, as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus. Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.

  3. Naturally transmitted herpesvirus papio-2 infection in a black and white colobus monkey.

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    Troan, Brigid V; Perelygina, Ludmila; Patrusheva, Irina; Wettere, Arnaud J van; Hilliard, Julia K; Loomis, Michael R; Voe, Ryan S De

    2007-12-15

    A 6.5-year-old female eastern black and white colobus monkey (Colobus guereza) was evaluated after acute onset of ataxia and inappetence. The monkey was ataxic and lethargic, but no other abnormalities were detected via physical examination, radiography, or clinicopathologic analyses. During the next 2 days, the monkey's clinical condition deteriorated, and its WBC count decreased dramatically. Cytologic examination of a CSF sample revealed marked lymphohistiocytic inflammation. Despite supportive care, the monkey became apneic; after 20 hours of mechanical ventilation, fatal cardiac arrest occurred. At necropsy, numerous petechiae were detected within the white matter tracts of the brain; microscopic lesions of multifocal necrosis and hemorrhage with intranuclear inclusions identified in the brain and adrenal glands were consistent with an acute herpesvirus infection. A specific diagnosis of herpesvirus papio-2 (HVP-2) infection was made on the basis of results of serologic testing; PCR assay of tissue specimens; live virus isolation from the lungs; and immunohistochemical identification of the virus within brain, spinal cord, and adrenal gland lesions. Via phylogenetic tree analysis, the colobus HVP-2 isolate was grouped with neuroinvasive strains of the virus. The virus was most likely transmitted to the colobus monkey through toys shared with a nearby colony of baboons (the natural host of HVP-2). To the authors' knowledge, this is the first reported case of natural transmission of HVP-2 to a nonhost species. Infection with HVP-2 should be a differential diagnosis for acute encephalopathy in primate monkeys and humans, particularly following exposure to baboons.

  4. IL-6 is Upregulated in Late-Stage Disease in Monkeys Experimentally Infected with Trypanosoma brucei rhodesiense

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    Dawn Nyawira Maranga

    2013-01-01

    Full Text Available The management of human African trypanosomiasis (HAT is constrained by lack of simple-to-use diagnostic, staging, and treatment tools. The search for novel biomarkers is, therefore, essential in the fight against HAT. The current study aimed at investigating the potential of IL-6 as an adjunct parameter for HAT stage determination in vervet monkey model. Four adult vervet monkeys (Chlorocebus aethiops were experimentally infected with Trypanosoma brucei rhodesiense and treated subcuratively at 28 days after infection (dpi to induce late stage disease. Three noninfected monkeys formed the control group. Cerebrospinal fluid (CSF and blood samples were obtained at weekly intervals and assessed for various biological parameters. A typical HAT-like infection was observed. The late stage was characterized by significant (P<0.05 elevation of CSF IL-6, white blood cell count, and total protein starting 35 dpi with peak levels of these parameters coinciding with relapse parasitaemia. Brain immunohistochemical staining revealed an increase in brain glial fibrillary acidic protein expression indicative of reactive astrogliosis in infected animals which were euthanized in late-stage disease. The elevation of IL-6 in CSF which accompanied other HAT biomarkers indicates onset of parasite neuroinvasion and show potential for use as an adjunct late-stage disease biomarker in the Rhodesian sleeping sickness.

  5. A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

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    Gormus, Bobby J; Martin, Louis N; Baskin, Gary B

    2004-01-01

    Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM). Our results together with observations of others led us to propose that both SIVmac and SIVDelta originated in SMM and that SIV emerged in humans as a result of early African nonhuman primate SIV trans-species infections in humans.

  6. Prevalence of Balantidium coli Infection in Bred Rhesus Monkeys (Macaca mulatta in Guangxi, southern China.

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    Hai Long Li

    2014-03-01

    Full Text Available Balantidium coli infects humans, primates and pigs, causing serious diarrhea and dysentery. Little information on the prevalence of B. coli in primates is available in China. This investigation was conducted to determine the prevalence of B. coli infection in bred rhesus monkeys in Guangxi Zhuang Nationality Autonomous Region (GZNAR, southern China.A total of 120 fecal samples were collected from rhesus monkeys bred in cages in GZNAR and B. coli cysts and/or trophozoites were examined microscopically after sedimentation with water in May 2013.(64.2% samples were tested positive. The prevalence was 65% (39/60 and 63.3% (38/60 in female and male monkeys, respectively. 80% (48/60 cages in this nonhuman primate center were positive for B. coli.The present survey revealed high circulation of B. coli in bred rhesus monkeys in GZNAR, which poses potential threats to animal and human health.

  7. Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys in Lake Ziway area, Ethiopia.

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    Teklemariam, Dejene; Legesse, Mengistu; Degarege, Abraham; Liang, Song; Erko, Berhanu

    2018-02-20

    To assess Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys (Chlorocebus aethiops) in Bochessa Village, Ziway, Ethiopia. Fecal specimens from selected schoolchildren and droppings of the vervet monkeys were collected and microscopically examined for intestinal parasites using the Kato-Katz thick smear and formol-ether concentration techniques. The prevalences of S. mansoni, Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, hookworms, Hymenolepis nana and Taenia species among the children were 35.7, 26.9, 24.1, 2.1, 2.1, 1.07 and 2.1%, respectively (by Kato-Katz) and 39.3, 36.1, 35.6, 2.9, 10.0, 4.3, and 2.9%, respectively (by formol-ether concentration). Prevalence of S. mansoni in vervet monkeys ranged from 10 to 20%. B. pfeifferi snails were exposed to S. mansoni miracidia from vervet origin, shed cercariae were then used to infect lab-bred albino mice. Adult worms were harvested from the mice 5 weeks post-exposure to cercariae to establish the schistosome life cycle and confirm the infection in the vervet monkeys. The natural infection of S. mansoni in vervet monkeys suggests that the non-human primate is likely to be implicated in the local transmission of schistosomiasis. Further epidemiological and molecular studies are needed to fully elucidate zoonotic role of non-human primate in the area.

  8. Bacterial infections in cynomolgus monkeys given small molecule immunomodulatory antagonists.

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    Price, Karen D

    2010-01-01

    Opportunistic infections (OIs) during the course of non-clinical toxicity studies can serve as a clinical indicator of immunosuppression. In monkeys, severity may be magnified since the possibility for fecal-oral and cage-to-cage transmission of bacteria exists, reserve capacity is low, and clinical signs of infection are not easily detected until the infectious process is well underway. This review summarizes a case study presented at the HESI-ILSI ITC-Sponsored workshop on Naturally Occurring Infections in Non-human Primates and Immunotoxicity Implications. It gives an overview on the impact of bacterial infections in monkeys on the development and regulatory assessment of three closely-related representative small molecule immunomodulatory (anti-inflammatory) drug candidates all inhibiting the same drug target. The infections, which sometimes progressed to bacteremia and death, originally manifested in the skin, upper respiratory tract, gastrointestinal tract, and less frequently as soft tissue abscesses. Infections were sporadic and not observed in all studies despite coverage of equivalent or higher systemic exposures or longer durations of treatment. To address concerns regarding inconsistency in the presentation and type of findings and their potential relationship to infection, steps were taken to identify causative agents (via culture, microscopy), implement various intervention and treatment regimens (supportive care, antibiotics, drug holiday), demonstrate reversibility of clinical and immune effects, and study major immune components/mechanisms affected (cytokine/stress protein profiling, immune cell phenotyping, and humoral/innate immune cell function tests). Appropriate diagnosis and characterization of the infection was critical to discrimination of these findings as a secondary pharmacologic effect rather than a direct drug-related target organ effect, and also guided clinical protocol design and regulatory acceptance.

  9. Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-α gene at an early stage of infection

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    Shimizu, Yuya; Miyazaki, Yasuyuki; Ibuki, Kentaro; Suzuki, Hajime; Kaneyasu, Kentaro; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi

    2005-01-01

    TNF-α has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-α against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-α gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4 + T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES and by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-α contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection

  10. Natural Gastric Infection with Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans

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    1994-01-01

    Methods: Infection and gastritis were have facilitated larger epidemiological studies. Another graded blindly by histological analysis and culture of...infec- with both types of bacteria by histological analysis and tion. Gastritis scores began to decrease 1 month after culture of H. pylori. In these 3...indicated that monkeys were not Infected. Gastritis score was :1.5 this organism belongs in the Helicobacter genus, and it in animals uninfected or

  11. Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.

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    Sakai, Kouji; Nagata, Noriyo; Ami, Yasushi; Seki, Fumio; Suzaki, Yuriko; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Fukushi, Shuetsu; Mizutani, Tetsuya; Yoshikawa, Tomoki; Otsuki, Noriyuki; Kurane, Ichiro; Komase, Katsuhiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Takeda, Makoto; Morikawa, Shigeru

    2013-01-01

    Canine distemper virus (CDV) has recently expanded its host range to nonhuman primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV) was isolated in Vero cells expressing dog signaling lymphocyte activation molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to the recent CDV outbreaks in China, suggesting continuing chains of CDV infection in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high virulence in experimentally infected cynomolgus monkeys and excreted progeny viruses in oral fluid and feces. These data revealed that some of the CDV strains, like CYN07-dV, have the potential to cause acute systemic infection in monkeys.

  12. Serological evidence for hepatitis e virus infection in laboratory monkeys and pigs in animal facilities in Japan.

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    Yamamoto, Hiroshi; Li, Tian-Cheng; Koshimoto, Chihiro; Ito, Kaori; Kita, Masakazu; Miyashita, Nobumoto; Arikawa, Jiro; Yagami, Kenichi; Asano, Masahide; Tezuka, Hideo; Suzuki, Noboru; Kurosawa, Tsutomu; Shibahara, Toshiyuki; Furuya, Masato; Mohri, Shirou; Sato, Hiroshi; Ohsawa, Kazutaka; Ibuki, Kentaro; Takeda, Naokazu

    2008-07-01

    In laboratory animal facilities, monkeys and pigs are used for animal experiments, but the details of hepatitis E virus (HEV) infection in these animals are unknown. The risk of infection from laboratory animals to humans has become a concern; therefore, much attention should be paid to the handling of these animals during their care and use, including surgical procedures performed on infected animals. In this connection, serum samples collected from 916 monkeys and 77 pigs kept in 23 animal facilities belonging to the Japanese Association of Laboratory Animal Facilities of National University Corporations (JALAN) and the Japanese Association of Laboratory Animal Facilities of Public and Private Universities (JALAP) in Japan were examined for the purpose of detecting antibodies to HEV and HEV RNA by using ELISA and RT-PCR, respectively. One hundred and seven serum samples of 916 (11.7%) monkeys were positive for anti-HEV IgG, and 7 and 17 serum samples of 916 (0.8% and 5.3%) monkeys were positive for anti-HEV IgM and IgA, respectively. Thirty-six samples from 62 (58.1%) farm pigs were positive for anti-HEV IgG, whereas all samples tested from miniature pigs were negative (0/15, 0%). Seven samples from 62 (9.1%) farm pigs and 7 samples from 916 (0.8%) monkeys were positive for IgM antibody, but these HEV-IgM antibody positive serum samples were HEV-RNA negative by RT-PCR. The IgM antibody positive rate (9.1%) of farm pigs was much higher than that of monkeys (0.8%). These results suggest the relative levels of risk of HEV infection from these animals to animal handlers and researchers who work with them in laboratory animal facilities.

  13. Dyscoria associated with herpesvirus infection in owl monkeys (Aotus nancymae)

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    Gozalo, Alfonso S.; Montoya, Enrique J.; Weller, Richard E.

    2008-08-16

    Abstract Dyscoria was observed in a female owl monkey and her two offspring. A third offspring was found dead with necrohemorrhagic encephalitis. Two males paired with the female died, one of which showed oral ulcers at necropsy. Histologic examination of the oral ulcers revealed syncytia and eosinophilic intranuclear inclusion bodies in epithelial cells. Ocular examination revealed posterior synechia associated with the dyscoria in all three animals. Serum samples from the female and her offspring were positive for Herpesvirus simplex antibodies by enzyme-linked immunosorbent assay. The clinical history, gross and microscopic lesions, and serology results suggests a herpesviral etiology, possibly, H. simplex or H. saimiri-1. This report underscores the risks associated with introducing animals into breeding or research colonies that were previously kept as pets or those from unknown origin that could carry asymptomatic pathogenic Herpesvirus infections. In addition, herpesviral infection should be considered among the differential diagnoses if dyscoria is observed in nonhuman primates.

  14. Coxsackievirus A 16 infection does not interfere with the specific immune response induced by an enterovirus 71 inactivated vaccine in rhesus monkeys.

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    Wang, Jingjing; Qi, Sudong; Zhang, Xiaolong; Zhang, Ying; Liu, Longding; Che, Yanchun; He, Zhanlong; Zhao, Yuan; Lu, Shuaiyao; Yu, Wenhai; Li, Qihan

    2014-07-31

    Hand, foot and mouth disease is usually caused by enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), which are members of the Picornaviridae family. In the present study, the characteristics of the immune response induced by an EV71 inactivated vaccine (made from human diploid cells) were explored in the presence of CA16 infection, based on the previously established neonatal rhesus monkey model. The typical clinical manifestations, including body temperature, viral viremia and virus shedding in the mouth, pharynx and feces, were characterized. A specific neutralizing antibody assay showed that the specific immune response induced by the EV71 inactivated vaccine was active against EV71 but not against CA16. No remarkable fluctuation in proinflammatory cytokine release was identified in the serum of immunized monkeys with EV71 vaccine and CA16 infections subsequently. The results showed that the specific immune response induced by the EV71 inactivated vaccine is effective against EV71 infection but is not affected by CA16 infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Generation of a human immunodeficiency virus type 1 chronically infected monkey B cell line expressing low levels of endogenous TRIM5alpha.

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    Ridolfi, Barbara; Catone, Stefania; Sgarbanti, Marco; Sernicola, Leonardo; Battistini, Angela; Parolin, Cristina; Titti, Fausto; Borsetti, Alessandra

    2009-12-01

    Several innate cellular antiviral factors exist in mammalian cells that prevent the replication of retroviruses. Among them, the tripartite motif protein (TRIM)5alpha has been shown to block human immunodeficiency virus type 1 (HIV-1) infection in several types of Old World monkey cells. Here we report a novel HIV-1 chronically infected monkey B cell line, F6/HIV-1, characterized by very low levels of TRIM5alpha expression that allows HIV-1 to overcome the restriction. Virus produced by F6/HIV-1 cells fails to infect monkey cells but retains the ability to infect human peripheral blood mononuclear cells (PBMCs) and T cell lines, although with a reduced infectivity compared to the input virus. Ultrastructural analyses revealed the presence of budding virions at the F6/HIV-1 cells plasma membrane characterized by a typical conical core shell. To our knowledge F6/HIV-1 is the first monkey cell line chronically infected by HIV-1 and able to release infectious particles thus representing a useful tool to gain further insights into the molecular mechanisms of HIV-1 pathogenesis.

  16. Induced Neurocysticercosis in Rhesus Monkeys (Macaca mulatta Produces Clinical Signs and Lesions Similar to Natural Disease in Man

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    N. Chowdhury

    2014-01-01

    Full Text Available Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of seizure and epilepsy in humans. The genesis of clinical manifestations of the disease through experimental animal models is poorly exploited. The monkeys may prove useful for the purpose due to their behavior and cognitive responses mimicking man. In this study, neurocysticercosis was induced in two rhesus monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given placebo. The monkeys given higher dose developed hyperexcitability, epileptic seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed delayed and milder clinical signs. On necropsy, all the infected monkeys showed numerous cysticerci in the brain. Histopathologically, heavily infected monkeys revealed liquefactive necrosis and formation of irregular cystic cavities lined by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In contrast, the monkeys infected with lower dose showed formation of typical foreign body granulomas characterized by central liquefaction surrounded by chronic inflammatory response. It was concluded that the inflammatory and immune response exerted by the host against cysticerci, in turn, led to histopathological lesions and the resultant clinical signs thereof.

  17. Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon.

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    Lalremruata, Albert; Magris, Magda; Vivas-Martínez, Sarai; Koehler, Maike; Esen, Meral; Kempaiah, Prakasha; Jeyaraj, Sankarganesh; Perkins, Douglas Jay; Mordmüller, Benjamin; Metzger, Wolfram G

    2015-09-01

    The quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now. We investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing. Based on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys. This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts.

  18. ZIKA VIRUS INFECTION IN AUSTRALIA FOLLOWING A MONKEY BITE IN INDONESIA.

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    Leung, Grace H Y; Baird, Robert W; Druce, Julian; Anstey, Nicholas M

    2015-05-01

    A traveller returning to Australia developed Zika virus infection, with fever, rash and conjunctivitis, with onset five days after a monkey bite in Bali, Indonesia. Flavivirus RNA detected on PCR from a nasopharyngeal swab was sequenced and identified as Zika virus. Although mosquito-borne transmission is also possible, we propose the bite as a plausible route of transmission. The literature for non-vector transmissions of Zika virus and other flaviviruses is reviewed.

  19. Capuchin monkeys do not show human-like pricing effects

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    Rhia eCatapano

    2014-12-01

    Full Text Available Recent work in judgment and decision-making has shown that a good’s price can have irrational effects on people’s preferences. People tend to prefer goods that cost more money and assume that such expensive goods will be more effective, even in cases where the price of the good is itself arbitrary. Although much work has documented the existence of these pricing effects, unfortunately little work has addressed where these price effects come from in the first place. Here we use a comparative approach to distinguish between different accounts of this bias and to explore the origins of these effects. Specifically, we test whether brown capuchin monkeys (Cebus apella are also susceptible to pricing effects within the context of an experimentally trained token economy. Using a capuchin population previously trained in a token market, we explored whether monkeys used price as an indicator of value across four experiments. Although monkeys demonstrated an understanding of which goods had which prices (consistently shifting preferences to cheaper goods when prices were increased, we observed no evidence that such price information affected their valuation of different kinds of goods. These results suggest that human price effects may involve more sophisticated human-unique cognitive capacities, such as an understanding of market forces and signaling.

  20. Capuchin monkeys do not show human-like pricing effects

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    Catapano, Rhia; Buttrick, Nicholas; Widness, Jane; Goldstein, Robin; Santos, Laurie R.

    2014-01-01

    Recent work in judgment and decision-making has shown that a good's price can have irrational effects on people's preferences. People tend to prefer goods that cost more money and assume that such expensive goods will be more effective, even in cases where the price of the good is itself arbitrary. Although much work has documented the existence of these pricing effects, unfortunately little work has addressed where these price effects come from in the first place. Here we use a comparative approach to distinguish between different accounts of this bias and to explore the origins of these effects. Specifically, we test whether brown capuchin monkeys (Cebus apella) are also susceptible to pricing effects within the context of an experimentally trained token economy. Using a capuchin population previously trained in a token market, we explored whether monkeys used price as an indicator of value across four experiments. Although monkeys demonstrated an understanding of which goods had which prices (consistently shifting preferences to cheaper goods when prices were increased), we observed no evidence that such price information affected their valuation of different kinds of goods. These results suggest that human pricing effects may involve more sophisticated human-unique cognitive capacities, such as an understanding of market forces and signaling. PMID:25520677

  1. Capuchin monkeys do not show human-like pricing effects.

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    Catapano, Rhia; Buttrick, Nicholas; Widness, Jane; Goldstein, Robin; Santos, Laurie R

    2014-01-01

    Recent work in judgment and decision-making has shown that a good's price can have irrational effects on people's preferences. People tend to prefer goods that cost more money and assume that such expensive goods will be more effective, even in cases where the price of the good is itself arbitrary. Although much work has documented the existence of these pricing effects, unfortunately little work has addressed where these price effects come from in the first place. Here we use a comparative approach to distinguish between different accounts of this bias and to explore the origins of these effects. Specifically, we test whether brown capuchin monkeys (Cebus apella) are also susceptible to pricing effects within the context of an experimentally trained token economy. Using a capuchin population previously trained in a token market, we explored whether monkeys used price as an indicator of value across four experiments. Although monkeys demonstrated an understanding of which goods had which prices (consistently shifting preferences to cheaper goods when prices were increased), we observed no evidence that such price information affected their valuation of different kinds of goods. These results suggest that human pricing effects may involve more sophisticated human-unique cognitive capacities, such as an understanding of market forces and signaling.

  2. Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys

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    Whitehead Stephen S

    2011-03-01

    Full Text Available Abstract Background Tahyna virus (TAHV is a human pathogen of the California encephalitis virus (CEV serogroup (Bunyaviridae endemic to Europe, Asia, and Africa. TAHV maintains an enzootic life cycle with several species of mosquito vectors and hares, rabbits, hedgehogs, and rodents serving as small mammal amplifying hosts. Human TAHV infection occurs in summer and early fall with symptoms of fever, headache, malaise, conjunctivitis, pharyngitis, and nausea. TAHV disease can progress to CNS involvement, although unlike related La Crosse virus (LACV, fatalities have not been reported. Human infections are frequent with neutralizing antibodies present in 60-80% of the elderly population in endemic areas. Results In order to determine the genomic sequence of wild-type TAHV, we chose three TAHV isolates collected over a 26-year period from mosquitoes. Here we present the first complete sequence of the TAHV S, M, and L segments. The three TAHV isolates maintained a highly conserved genome with both nucleotide and amino acid sequence identity greater than 99%. In order to determine the extent of genetic relatedness to other members of the CEV serogroup, we compared protein sequences of TAHV with LACV, Snowshoe Hare virus (SSHV, Jamestown Canyon virus (JCV, and Inkoo virus (INKV. By amino acid comparison, TAHV was most similar to SSHV followed by LACV, JCV, and INKV. The sequence of the GN protein is most conserved followed by L, N, GC, NSS, and NSM. In a weanling Swiss Webster mouse model, all three TAHV isolates were uniformly neurovirulent, but only one virus was neuroinvasive. In rhesus monkeys, the virus was highly immunogenic even in the absence of viremia. Cross neutralization studies utilizing monkey immune serum demonstrated that TAHV is antigenically distinct from North American viruses LACV and JCV. Conclusions Here we report the first complete sequence of TAHV and present genetic analysis of new-world viruses, LACV, SSHV, and JCV with old

  3. Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

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    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.

  4. Co-infection patterns of intestinal parasites in arboreal primates (proboscis monkeys, Nasalis larvatus in Borneo

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    Annette Klaus

    2017-12-01

    Full Text Available Non-human primates of South-East Asia remain under-studied concerning parasite epidemiology and co-infection patterns. Simultaneously, efforts in conservation demand knowledge of parasite abundance and biodiversity in threatened species. The Endangered proboscis monkey, Nasalis larvatus, a primate flagship species for conservation in Borneo, was investigated in the present study. Habitat loss and fragmentation are among the greatest threats to bachelor and harem groups of this folivorous colobine. Designed as a follow-up study, prevalence and co-infection status of intestinal parasites from N. larvatus in a protected area in Malaysian Borneo were analyzed from fecal samples using a flotation method. For the first time, the intestinal parasite co-infection patterns were examined using quantitative analyses. Overall, 92.3% of fecal samples (N = 652 were positive for helminth eggs. Five helminth groups were detected: (1 trichurids (82.7% prevalence including Trichuris spp. (82.1% and Anatrichosoma spp. (1.4%, (2 strongyles (58.9% including Trichostrongylus spp. (48.5% and Oesophagostomum/Ternidens spp. (22.8%, (3 Strongyloides fuelleborni (32.7%, (4 Ascaris lumbricoides (8.6%, and (5 Enterobius spp. (5.5%. On average, an individual was co-infected with two different groups. Significant positive associations were found for co-infections of trichurids with strongyles and S. fuelleborni as well as S. fuelleborni with A. lumbricoides and strongyles. This study shows a high prevalence of various gastrointestinal helminths with potential transmission pathways primarily related to soil and with zoonotic relevance in wild proboscis monkeys in their remaining natural habitats. Observed positive associations of trichurids with strongyles and Strongyloides spp. may result from the high prevalence of trichurids. Similarly, positive associations between Strongyloides and Ascaris were found, both of which typically occur predominantly in juvenile hosts

  5. Molecular characterization of trypanosomatid infections in wild howler monkeys (Alouatta caraya in northeastern Argentina

    Directory of Open Access Journals (Sweden)

    Mariela Florencia Martínez

    2016-08-01

    Full Text Available The transmission of Trypanosoma cruzi by vectors is confined to the Americas, and the infection circulates in at least two broadly defined transmission cycles occurring in domestic and sylvatic habitats. This study sought to detect and characterize infection by T. cruzi and other trypanosomes using PCR strategies in blood samples from free-ranging howler monkeys, Alouatta caraya, in the northeastern Argentina. Blood samples were collected at four sites with variable levels of habitat modification by human activity. PCR was conducted using primers for kinetoplast DNA, satellite DNA and ribosomal DNA of the trypanosomatid parasites. Ribosomal and satellite DNA fragments were sequenced to identify the trypanosomatid species and to characterize the discrete typing units (DTUs of T. cruzi. Overall, 46% (50/109 of the howlers were positive according to the kDNA-PCR assay, but only 7 of the howlers were positive according to the SatDNA-PCR protocol. We sequenced the amplicons of the satellite DNA obtained from five specimens, and the sequences were 99% and 100% similar to T. cruzi. A sequence typical of DTU T. cruzi I was found in one howler monkey from the “remote” site, while sequences compatible with DTUs II, V, and VI were found in howlers from the “remote”, “rural” and “village” sites. We detected 96% positive samples for RibDNA-PCR, 9 of which were sequenced and displayed 99% identity with Trypanosoma minasense, while none showed identity with T. cruzi. The results demonstrated the presence of T. cruzi and a species closely related to T. minasense in blood samples from free-ranging A. caraya, belonging to different T. cruzi DTUs circulating in these howler monkey populations. The results obtained in this study could help evaluate the role of A. caraya as a reservoir of T. cruzi in regions where Chagas disease is hyper-endemic and where the human-wildlife interface is increasing.

  6. Circular viral DNA detection and junction sequence analysis from PBMC of SHIV-infected cynomolgus monkeys with undetectable virus plasma RNA

    International Nuclear Information System (INIS)

    Cara, Andrea; Maggiorella, Maria Teresa; Bona, Roberta; Sernicola, Leonardo; Baroncelli, Silvia; Negri, Donatella R.M.; Leone, Pasqualina; Fagrouch, Zahra; Heeney, Jonathan; Titti, Fausto; Cafaro, Aurelio; Ensoli, Barbara

    2004-01-01

    Extrachromosomal forms of human immunodeficiency virus (HIV)-1 can be detected in peripheral blood mononuclear cell (PBMC) from HIV-infected patients in the absence of detectable viral replication and are thought to be a sign of active but cryptic virus replication. No information, however, are available on whether these forms are also present in animal models for acquired immunodeficiency syndrome (AIDS) and on their relation with other methods of detection of virus replication. To this aim, a polymerase chain reaction (PCR) approach was used to detect and analyze unintegrated circular 2-LTR-containing forms in PBMC of simian human immunodeficiency virus (SHIV)89.6P infected cynomolgus monkeys with RNA levels ranging between 1.8x10 6 and less than 50 copies/ml of plasma. 2-LTR forms were detected in 96.5% of monkeys' samples above 50 copies/ml of plasma, whereas they were present in 75.8% of monkeys' samples below 50 copies/ml of plasma. Persistence of unintegrated viral DNA in monkeys with undetectable plasma RNA could indicate either stability in non-dividing cells or ongoing low levels of viral replication in dividing cells

  7. Monkey Bites among US Military Members, Afghanistan, 2011

    Science.gov (United States)

    Baker, Katheryn A.

    2012-01-01

    Bites from Macaca mulatta monkeys, native to Afghanistan, can cause serious infections. To determine risk for US military members in Afghanistan, we reviewed records for September–December 2011. Among 126 animal bites and exposures, 10 were monkey bites. Command emphasis is vital for preventing monkey bites; provider training and bite reporting promote postexposure treatment. PMID:23017939

  8. Pathology of experimental Ebola virus infection in African green monkeys. Involvement of fibroblastic reticular cells.

    Science.gov (United States)

    Davis, K J; Anderson, A O; Geisbert, T W; Steele, K E; Geisbert, J B; Vogel, P; Connolly, B M; Huggins, J W; Jahrling, P B; Jaax, N K

    1997-08-01

    Ebola virus has been responsible for explosive lethal outbreaks of hemorrhagic fever in both humans and nonhuman primates. Previous studies showed a predilection of Ebola virus for cells of the mononuclear phagocyte system and endothelial cells. To examine the distribution of lesions and Ebola virus antigen in the tissues of six adult male African green monkeys (Cercopithecus aethiops) that died 6 to 7 days after intraperitoneal inoculation of Ebola-Zaire (Mayinga) virus. Tissues were examined histologically, immunohistochemically, and ultrastructurally. A major novel finding of this study was that fibroblastic reticular cells were immunohistochemically and ultrastructurally identified as targets of Ebola virus infection. The role of Ebola virus-infected fibroblastic reticular cells in the pathogenesis of Ebola hemorrhagic fever warrants further investigation. This is especially important because of recent observations indicating that fibroblastic reticular cells, along with the reticular fibers they produce, maximize the efficiency of the immune response.

  9. Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

    International Nuclear Information System (INIS)

    Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L.

    1991-01-01

    Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV mac ) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV mac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV mac activity in vitro. Plasma of these animals efficiently blocks SIV mac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV mac -infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4 + but not CD8 + concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

  10. Molecular characterization of Blastocystis isolates from children and rhesus monkeys in Kathmandu, Nepal.

    Science.gov (United States)

    Yoshikawa, Hisao; Wu, Zhiliang; Pandey, Kishor; Pandey, Basu Dev; Sherchand, Jeevan Bahadur; Yanagi, Tetsuo; Kanbara, Hiroji

    2009-03-23

    To investigate the possible transmission of Blastocystis organisms between local rhesus monkeys and children in Kathmandu, Nepal, we compared the subtype (ST) and sequence of Blastocystis isolates from children with gastrointestinal symptoms and local rhesus monkeys. Twenty and 10 Blastocystis isolates were established from 82 and 10 fecal samples obtained from children and monkeys, respectively. Subtype analysis with seven sequence-tagged site (STS) primers indicated that the prevalence of Blastocystis sp. ST1, ST2 and ST3 was 20%, 20% and 60% in the child isolates, respectively. In contrast to human isolates, ST3 was not found in monkey isolates and the prevalence of ST1 and ST2 was 50% and 70%, respectively, including three mixed STs1 and 2 and one isolate not amplified by any STS primers, respectively. Since Blastocystis sp. ST2 has been reported as the most dominant genotype in the survey of Blastocystis infection among the various monkey species, sequence comparison of the 150bp variable region of the small subunit rRNA (SSU rRNA) gene was conducted among ST2 isolates of humans and monkeys. Sequence alignment of 24 clones developed from ST2 isolates of 4 humans and 4 monkeys showed three distinct subgroups, defined as ST2A, ST2B and ST2C. These three subgroups were shared between the child and monkey isolates. These results suggest that the local rhesus monkeys are a possible source of Blastocystis sp. ST2 infection of humans in Kathmandu.

  11. Patterns of Infection and Patterns of Evolution: How a Malaria Parasite Brought "Monkeys and Man" Closer Together in the 1960s.

    Science.gov (United States)

    Mason Dentinger, Rachel

    2016-04-01

    In 1960, American parasitologist Don Eyles was unexpectedly infected with a malariaparasite isolated from a macaque. He and his supervisor, G. Robert Coatney of the National Institutes of Health, had started this series of experiments with the assumption that humans were not susceptible to "monkey malaria." The revelation that a mosquito carrying a macaque parasite could infect a human raised a whole range of public health and biological questions. This paper follows Coatney's team of parasitologists and their subjects: from the human to the nonhuman; from the American laboratory to the forests of Malaysia; and between the domains of medical research and natural history. In the course of this research, Coatney and his colleagues inverted Koch's postulate, by which animal subjects are used to identify and understand human parasites. In contrast, Coatney's experimental protocol used human subjects to identify and understand monkey parasites. In so doing, the team repeatedly followed malaria parasites across the purported boundary separating monkeys and humans, a practical experience that created a sense of biological symmetry between these separate species. Ultimately, this led Coatney and his colleagues make evolutionary inferences, concluding "that monkeys and man are more closely related than some of us wish to admit." In following monkeys, men, and malaria across biological, geographical, and disciplinary boundaries, this paper offers a new historical narrative, demonstrating that the pursuit of public health agendas can fuel the expansion of evolutionary knowledge.

  12. Induction of encephalitis in rhesus monkeys infused with lymphocryptovirus-infected B-cells presenting MOG(34-56 peptide.

    Directory of Open Access Journals (Sweden)

    Krista G Haanstra

    Full Text Available The overlapping epidemiology of multiple sclerosis (MS and Epstein-Barr virus (EBV, the increased risk to develop MS after infectious mononucleosis (IM and the localization of EBV-infected B-cells within the MS brain suggest a causal link between EBV and MS. However, the underlying mechanism is unknown. We hypothesize that EBV-infected B-cells are capable of eliciting a central nervous system (CNS targeting autoimmune reaction. To test this hypothesis we have developed a novel experimental model in rhesus monkeys of IM-like disease induced by infusing autologous B-lymphoblastoid cells (B-LCL. Herpesvirus papio (HVP is a lymphocryptovirus related to EBV and was used to generate rhesus monkey B-LCL. Three groups of five animals were included; each group received three intravenous infusions of B-LCL that were either pulsed with the encephalitogenic self peptide MOG(34-56 (group A, a mimicry peptide (981-1003 of the major capsid protein of cytomegalovirus (CMVmcp(981-1003; group B or the citrullinated MOG(34-56 (cMOG(34-56; group C. Groups A and B received on day 98 a single immunization with MOG(34-56 in incomplete Freund's adjuvant (IFA. Group C monkeys were euthanized just prior to day 98 without booster immunization. We observed self-peptide-specific proliferation of T-cells, superimposed on similar strong proliferation of CD3(+CD8(+ T-cells against the B-LCL as observed in IM. The brains of several monkeys contained perivascular inflammatory lesions of variable size, comprising CD3(+ and CD68(+ cells. Moreover, clusters of CD3(+ and CD20(+ cells were detected in the meninges. The only evident clinical sign was substantial loss of bodyweight (>15%, a symptom observed both in early autoimmune encephalitis and IM. In conclusion, this model suggests that EBV-induced B-LCL can elicit a CNS targeting inflammatory (autoimmune reaction.

  13. Aotus infulatus monkey is susceptible to Plasmodium falciparum infection and may constitute an alternative experimental model for malaria

    Directory of Open Access Journals (Sweden)

    Carvalho Leonardo JM

    2000-01-01

    Full Text Available Aotus is one of the WHO-recommended primate models for studies in malaria, and several species can be infected with Plasmodium falciparum or P. vivax. Here we describe the successful infection of the species A. infulatus from eastern Amazon with blood stages of P. falciparum. Both intact and splenectomized animals were susceptible to infection; the intact ones were able to keep parasitemias at lower levels for several days, but developed complications such as severe anemia; splenectomized monkeys developed higher parasitemias but no major complications. We conclude that A. infulatus is susceptible to P. falciparum infection and may represent an alternative model for studies in malaria.

  14. Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.

    Directory of Open Access Journals (Sweden)

    Cristiano Marcelo Espinola Carvalho

    Full Text Available BACKGROUND: The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2 is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2(-/- mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY: Rhesus monkeys and C57BL/6 and Nos2(-/- mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2(+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG, echocardiogram (ECHO, creatine kinase heart isoenzyme (CK-MB activity levels in serum and connexin 43 (Cx43 expression in the cardiac tissue. RESULTS: Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC. Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2(+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2(-/- mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. CONCLUSION: T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute

  15. Immunospecific immunoglobulins and IL-10 as markers for Trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys

    DEFF Research Database (Denmark)

    Ngotho, Maina; Kagira, J.M.; Jensen, Henrik Michael Elvang

    2009-01-01

    and 140 days post-infection (dpi) respectively. Matched serum and CSF samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) and IL-10 were quantified by ELISA. RESULTS: There was no detectable immunospecific IgM and IgG in the CSF before 49 dpi. CSF IgM and Ig......OBJECTIVE: To determine the usefulness of IL-10 and immunoglobulin M (IgM) as biomarkers for staging HAT in vervet monkeys, a useful pathogenesis model for humans. METHODS: Vervet monkeys were infected with Trypanosoma brucei rhodesiense and subsequently given sub-curative and curative treatment 28...... curative treatment was given. After curative treatment, there was rapid and significant drop in serum IgM and IL-10 concentration as well as CSF WCC. However, the CSF IgM and IgG remained detectable to the end of the study. CONCLUSIONS: Serum and CSF concentrations of immunospecific IgM and CSF IgG changes...

  16. Transmission of naturally occurring lymphoma in macaque monkeys.

    OpenAIRE

    Hunt, R D; Blake, B J; Chalifoux, L V; Sehgal, P K; King, N W; Letvin, N L

    1983-01-01

    Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and ...

  17. Monkey-based research on human disease: the implications of genetic differences.

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.

  18. Comparative Infectivity Determinations of Dengue Virus Vaccine Candidates in Rhesus Monkeys, Mosquitoes, and Cell Cultures

    Science.gov (United States)

    1993-01-28

    34 are required for the evaluation of these vaccine candidates. RE: DAMDI7-89-C-9175 Page 16 REFERENCES 1. Sabin AB, Sclesinger RW, 1945. Production of...AD-A261 892 CONTRACT NO: DAMD17-89-C-9 175 \\II\\IllI\\I\\I1\\\\~il\\ TITLE: COMPARATIVE INFECTIVITY DETERMINATIONS OF DENGUE VIRUS VACCINE CANDIDATES IN... Vaccine Candidates in Rhesus Monkeys, 63002A Mosquitoes, and Cell Cultures 3M263002D870 AC 6. AUTHOR(S) DA335475 Edmundo Kraiselburd 7. PERFORMING

  19. Induction of Encephalitis in Rhesus Monkeys Infused with Lymphocryptovirus-Infected B-Cells Presenting MOG34–56 Peptide

    Science.gov (United States)

    Haanstra, Krista G.; Wubben, Jacqueline A. M.; Jonker, Margreet; Hart, Bert A. ‘t.

    2013-01-01

    The overlapping epidemiology of multiple sclerosis (MS) and Epstein-Barr virus (EBV), the increased risk to develop MS after infectious mononucleosis (IM) and the localization of EBV-infected B-cells within the MS brain suggest a causal link between EBV and MS. However, the underlying mechanism is unknown. We hypothesize that EBV-infected B-cells are capable of eliciting a central nervous system (CNS) targeting autoimmune reaction. To test this hypothesis we have developed a novel experimental model in rhesus monkeys of IM-like disease induced by infusing autologous B-lymphoblastoid cells (B-LCL). Herpesvirus papio (HVP) is a lymphocryptovirus related to EBV and was used to generate rhesus monkey B-LCL. Three groups of five animals were included; each group received three intravenous infusions of B-LCL that were either pulsed with the encephalitogenic self peptide MOG34–56 (group A), a mimicry peptide (981–1003) of the major capsid protein of cytomegalovirus (CMVmcp981–1003; group B) or the citrullinated MOG34–56 (cMOG34–56; group C). Groups A and B received on day 98 a single immunization with MOG34–56 in incomplete Freund’s adjuvant (IFA). Group C monkeys were euthanized just prior to day 98 without booster immunization. We observed self-peptide-specific proliferation of T-cells, superimposed on similar strong proliferation of CD3+CD8+ T-cells against the B-LCL as observed in IM. The brains of several monkeys contained perivascular inflammatory lesions of variable size, comprising CD3+ and CD68+ cells. Moreover, clusters of CD3+ and CD20+ cells were detected in the meninges. The only evident clinical sign was substantial loss of bodyweight (>15%), a symptom observed both in early autoimmune encephalitis and IM. In conclusion, this model suggests that EBV-induced B-LCL can elicit a CNS targeting inflammatory (auto)immune reaction. PMID:23977076

  20. Canine distemper outbreak in rhesus monkeys, China.

    Science.gov (United States)

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-08-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People's Republic of China. Approximately 10,000 animals were infected (25%-60% disease incidence); 5%-30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  1. [Hybrids of human and monkey adenoviruses (adeno-adeno hybrids) that can reproduce in monkey cells: biological and molecular genetic peculiarities].

    Science.gov (United States)

    Grinenko, N F; Savitskaia, N V; Pashvykina, G V; Al'tshteĭn, A D

    2003-06-01

    A highly oncogenic monkey adenovirus SA7(C8) facilitates the reproduction of human adenovirus type 2 (Ad2) in monkey cells. Upon mixed infection of monkey cells with both viruses, these viruses recombine producing defective adeno-adeno hybrids Ad2C8 serologically identical to Ad2 and capable of assisting Ad2 to reproduce in monkey cells. Ad2C8 and Ad2 form an intercomplementary pair inseparable in monkey cells. Unlike oncogenic SA7(C8), Ad2C8 is a nononcogenic virus for hamsters but is able to induce tumor antigens of this virus (T and TSTA). Molecular genetic analysis of 68 clones of adeno-adeno hybrids revealed that the left part of their genome consists of Ad2 DNA, and the right part contains no less than 40% of the viral SA7(C8) genome where E2A, E3, and E4 genes are located. Apparently, the products of these genes contribute to the composition of adenoviral tumor antigens, while the E4 gene is involved in complementation of monkey and human adenoviruses and makes a contribution to host range determination of these viruses.

  2. Emergence of Cryptosporidium hominis Monkey Genotype II and Novel Subtype Family Ik in the Squirrel Monkey (Saimiri sciureus) in China.

    Science.gov (United States)

    Liu, Xuehan; Xie, Na; Li, Wei; Zhou, Ziyao; Zhong, Zhijun; Shen, Liuhong; Cao, Suizhong; Yu, Xingming; Hu, Yanchuan; Chen, Weigang; Peng, Gangneng

    2015-01-01

    A single Cryptosporidium isolate from a squirrel monkey with no clinical symptoms was obtained from a zoo in Ya'an city, China, and was genotyped by PCR amplification and DNA sequencing of the small-subunit ribosomal RNA (SSU rRNA), 70-kDa heat shock protein (HSP70), Cryptosporidium oocyst wall protein, and actin genes. This multilocus genetic characterization determined that the isolate was Cryptosporidium hominis, but carried 2, 10, and 6 nucleotide differences in the SSU rRNA, HSP70, and actin loci, respectively, which is comparable to the variations at these loci between C. hominis and the previously reported monkey genotype (2, 3, and 3 nucleotide differences). Phylogenetic studies, based on neighbor-joining and maximum likelihood methods, showed that the isolate identified in the current study had a distinctly discordant taxonomic status, distinct from known C. hominis and also from the monkey genotype, with respect to the three loci. Restriction fragment length polymorphisms of the SSU rRNA gene obtained from this study were similar to those of known C. hominis but clearly differentiated from the monkey genotype. Further subtyping was performed by sequence analysis of the gene encoding the 60-kDa glycoprotein (gp60). Maximum homology of only 88.3% to C. hominis subtype IdA10G4 was observed for the current isolate, and phylogenetic analysis demonstrated that this particular isolate belonged to a novel C. hominis subtype family, IkA7G4. This study is the first to report C. hominis infection in the squirrel monkey and, based on the observed genetic characteristics, confirms a new C. hominis genotype, monkey genotype II. Thus, these results provide novel insights into genotypic variation in C. hominis.

  3. [Monkey-pox, a model of emergent then reemergent disease].

    Science.gov (United States)

    Georges, A J; Matton, T; Courbot-Georges, M C

    2004-01-01

    The recent emergence of monkey pox in the United States of America highlights the problem (known for other infectious agents) of dissemination of pathogens outside their endemic area, and of subsequent global threats of variable gravity according to agents. It is a real emergency since monkey pox had been confined to Africa for several decades, where small epidemics occurred from time to time, monkey pox is a "miniature smallpox" which, in Africa, evolves on an endemic (zoonotic) mode with, as reservoirs, several species of wild rodents (mainly squirrels) and some monkey species. It can be accidentally transmitted to man then develops as epidemics, sometimes leading to death. The virus was imported in 2003 in the United States of America, via Gambia rats and wild squirrels (all African species), and infected prairie dogs (which are now in fashion as pets), then crossed the species barrier to man. In the United States of America, screening campaigns, epidemiological investigations, and subsequent treatments led to a rapid control of the epidemic, which is a model of emergent disease for this country. Therapeutic and preventive measures directly applicable to monkey pox are discussed. They can also be applied against other pox virus infections (including smallpox). The risk of criminal introduction of pox viruses is discussed since it is, more than ever, a real worldwide threat.

  4. Response of sublethally irradiated monkeys to a replicating viral antigen

    International Nuclear Information System (INIS)

    Hilmas, D.E.; Spertzel, R.O.

    1975-01-01

    Temporal effects of exposure to sublethal, total-body x radiation (400 R) on responses to vaccination with the attenuated Venezuelan equine encephalomyelitis vaccine virus, TC-83, were examined in rhesus monkeys. Viremia, often with delayed onset, was prolonged even when irradiation preceded vaccination by 28 days. Virus titers were increased, particularly in groups irradiated 4 or 7 days before vaccination. Delay in appearance of hemagglutination-inhibition and serum-neutralizing antibody correlated closely with persistence of viremia in irradiated-vaccinated monkeys. The temporal course of antibody response was markedly affected by the interval between irradiation and injection of this replicating antigen. With longer intervals between irradiation and vaccination, the somewhat depressed antibody responses approached normal or surpassed those of nonirradiated monkeys. Vaccination 14 days after radiation exposure resulted in lethality to 8 of 12 monkeys, apparently as a result of secondary infection. The additional lymphopenic stress due to the effect of TC-83, superimposed on the severely depressed hematopoietic competence at 14 days, undoubtedly contributed to this increased susceptibility to latent infection

  5. Global gene expression analysis of peripheral blood mononuclear cells in rhesus monkey infants with CA16 infection-induced HFMD.

    Science.gov (United States)

    Song, Jie; Hu, Yajie; Hu, Yunguang; Wang, Jingjing; Zhang, Xiaolong; Wang, Lichun; Guo, Lei; Wang, Yancui; Ning, Ruotong; Liao, Yun; Zhang, Ying; Zheng, Huiwen; Shi, Haijing; He, Zhanlong; Li, Qihan; Liu, Longding

    2016-03-02

    Coxsackievirus A16 (CA16) is a dominant pathogen that results in hand, foot, and mouth disease and causes outbreaks worldwide, particularly in the Asia-Pacific region. However, the underlying molecular mechanisms remain unclear. Our previous study has demonstrated that the basic CA16 pathogenic process was successfully mimicked in rhesus monkey infant. The present study focused on the global gene expression changes in peripheral blood mononuclear cells of rhesus monkey infants with hand, foot, and mouth disease induced by CA16 infection at different time points. Genome-wide expression analysis was performed with Agilent whole-genome microarrays and established bioinformatics tools. Nine hundred and forty-eight significant differentially expressed genes that were associated with 5 gene ontology categories, including cell communication, cell cycle, immune system process, regulation of transcription and metabolic process were identified. Subsequently, the mapping of genes related to the immune system process by PANTHER pathway analysis revealed the predominance of inflammation mediated by chemokine and cytokine signaling pathways and the interleukin signaling pathway. Ultimately, co-expressed genes and their networks were analyzed. The results revealed the gene expression profile of the immune system in response to CA16 in rhesus monkey infants and suggested that such an immune response was generated as a result of the positive mobilization of the immune system. This initial microarray study will provide insights into the molecular mechanism of CA16 infection and will facilitate the identification of biomarkers for the evaluation of vaccines against this virus. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Pentatrichomonas hominis: prevalence and molecular characterization in humans, dogs, and monkeys in Northern China.

    Science.gov (United States)

    Li, Wen-Chao; Ying, Meng; Gong, Peng-Tao; Li, Jian-Hua; Yang, Ju; Li, He; Zhang, Xi-Chen

    2016-02-01

    Pentatrichomonas hominis is an anaerobic amitochondrial flagellated protist that primarily colonizes the large intestines of a number of species, including cats, dogs, nonhuman primates, and humans. The prevalence of this parasite in dogs, monkeys, and humans is, however, poorly understood. In this study, a total of 362 fecal samples including 252 dogs, 60 monkeys, and 50 humans from northern China were collected for an epidemiological survey of P. hominis infection.The average prevalence of P. hominis infection determined by nested PCR was 27.38% (69/252), 4.00% (2/50), and 46.67% (28/60) in dogs, humans, and monkeys, respectively. The prevalence was significantly higher in 6-month-old dogs (41.53%) and children (7.69%) than in older dogs (14.39%) and adults (0%) (P dogs, monkeys, and humans, especially in children and young dogs. Given the infection prevalence, P. hominis may pose a risk of zoonotic and anthroponotic transmission.

  7. Monkey-derived monoclonal antibodies against Plasmodium falciparum

    International Nuclear Information System (INIS)

    Stanley, H.A.; Reese, R.T.

    1985-01-01

    A system has been developed that allows efficient production of monkey monoclonal antibodies from owl monkeys. Splenocytes or peripheral blood lymphocytes from monkeys immune to the human malarial parasite, Plasmodium falciparum, were fused with P3X63 Ag8.653 mouse myelomas. The resulting hybridomas were screened by an indirect fluorescent antibody test for the production of monkey monoclonal antibodies (mAb) reactive with P. falciparum. Most of the mAb reacted with the P. falciparum merozoites and immunoprecipitated a parasite-derived glycoprotein having a relative molecular weight of 185,000. These mAb gave a minimum of five different immunoprecipitation patterns, thus demonstrating that a large number of polypeptides obtained when parasitized erythrocytes are solubilized share epitopes with this large glycoprotein. In addition, mAb were obtained that reacted with antigens associated with the infected erythrocyte membrane. One of these mAb bound a M/sub r/ 95,000 antigen. Radioimmunoprecipitation assays using 125 T-antibodies were done

  8. Molecular characterization and epidemiological investigation of Cryptosporidium hominis IkA18G1 and C. hominis monkey genotype IiA17, two unusual subtypes diagnosed in Swedish patients.

    Science.gov (United States)

    Lebbad, Marianne; Winiecka-Krusnell, Jadwiga; Insulander, Mona; Beser, Jessica

    2018-05-01

    Cryptosporidium hominis is considered a strictly human-adapted species, and it is only occasionally diagnosed in animals. However, two variants, C. hominis monkey genotype and C. hominis Ik, were originally described in non-human hosts, monkeys and horses, respectively. During a Swedish national Cryptosporidium study, where all samples were analyzed at the small subunit rRNA and the 60 kDa (gp60) glycoprotein loci, we identified two patients infected with C. hominis monkey genotype (subtype IiA17) and two infected with C. hominis subtype IkA18G1. The isolates were further analyzed at the actin and the 70 kDa heat shock protein loci, and these analyses showed that these two subtype families are closely related to each other and to human-adapted C. hominis as well as to Cryptosporidium cuniculus. The two patients with C. hominis monkey genotype infection (a father and son) had visited a monkey farm in Thailand prior to infection, while the two cases with C. hominis Ik were unrelated, both probably infected in Sweden. This is the first time that a monkey genotype infection in humans has been related to contact with monkeys and where the gp60 subtype was identified. It is also the first time that human infection caused by C. hominis subtype Ik is described. Even though we were not able to detect any parasites in the animal samples, zoonotic transmission cannot be ruled out in any of these cases because both subtype families are regarded as animal adapted. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Pathogenesis of Rift Valley Fever in Rhesus Monkeys: Role of Interferon Response

    Science.gov (United States)

    1990-01-01

    hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived...DMI, FILE Copy Arch Virol (1990) 110: 195-212 Amhivesirology ( by Springer-Verlag 1990 00 N Pathogenesis of Rift Valley fever in rhesus monkeys: (NI...inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys

  10. 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.

  11. Canine Distemper Outbreak in Rhesus Monkeys, China

    Science.gov (United States)

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang

    2011-01-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People’s Republic of China. Approximately 10,000 animals were infected (25%–60% disease incidence); 5%–30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain. PMID:21801646

  12. Kyasanur forest disease virus: viremia and challenge studies in monkeys with evidence of cross-protection by Langat virus infection [v1; ref status: indexed, http://f1000r.es/UiWGcy

    Directory of Open Access Journals (Sweden)

    Keerti V Shah

    2012-12-01

    Full Text Available Kyasanur Forest Disease Virus (KFDV, discovered in 1957, is a member of the tick-borne encephalitis virus (TBEV complex. Diseases caused by members of the TBEV complex occur in many parts of the world. KFDV produces a hemorrhagic fever in humans in South India and fatal illnesses in both species of monkeys in the area, the black faced langur (Presbytis entellus and the bonnet macaque (Macaca radiata. Experimental infection of the langur and the bonnet macaque with early mouse passage KFDV strain P9605 resulted in a viremia of up to 11 days duration, peak viremia titers as high as 109, and death in 82 = 100% of the animals. Prolonged passage of the KFDV strain P9605 in monkey kidney tissue culture resulted in a markedly reduced virulence of the virus for both species; peak viremia titers in monkeys decreased by 2.5 to 4.0 log LD 50 (p= 0.001, and the mortality decreased to 10% (p= 0.001. In challenge experiments, monkeys previously infected with tissue-culture-adapted KFDV, or with the related Langat virus from Malaysia, were fully protected against virulent KFDV. These studies in non-human primates lend support to the idea that a live virus vaccine from a member of the TBEV complex may be broadly protective against infections by other members of the TBEV complex.

  13. Attempts at immunization against Malayan filariasis using X-irradiated infective larvae

    International Nuclear Information System (INIS)

    Ramachandran, C.P.

    1975-01-01

    Recent studies on immunity to helminthic infections have shown that some degree of protective immunity may be stimulated by inoculations of attenuated living worms or their metabolites. Although much on these lines has been done with several helminths, little if any has been done with filarial infections in general. Experiments were designed to observe the effects of attempted immunization in the rhesus monkey as well as the domestic cat by the use of attenuated infective larvae of Brugia malayi. The sub-periodic strain of Brugia malayi, the major filarial parasite of man in Malaysia, maintained in the laboratory on experimentally infected cats and rhesus monkeys were used for the preparation of X-irradiated vaccines as well as for challenge inoculations. Third-stage infective larvae of Brugia malayi were obtained from experimentally fed Aedes togoi mosquitoes. Infective larvae were irradiated by X-rays, using a Dermopan X-ray unit at exposures between 10 - 40 kR. Rhesus monkeys and cats were inoculated twice with 100 - 400 attenuated larvae per inoculation at 2 week intervals and challenged about a month later by inoculation of 100 normal larvae. Control animals for each vaccination dose as well as for challenge doses were maintained. In rhesus monkeys persistent immunity to challenge infections (expressed as failure to cause microfilaraemia) were obtained in animals vaccinated with 200 infective larvae attenuated by X-irradiation at 20000 R. Encouraged with the results obtained on rhesus monkeys, similar experiments on an enlarged scale using varying strengths of the vaccines were carried out on the domestic cat, which is a more receptive animal host for Brugia malayi. However, all cats vaccinated when challenged came down with patent infection indicating lack of any definite immunity. In all these experiments, results of vaccine control animals showed that inoculation of irradiated larvae was not followed by the infection of microfilaria in the blood, indicating

  14. Comparative analysis of field-isolate and monkey-adapted Plasmodium vivax genomes.

    Science.gov (United States)

    Chan, Ernest R; Barnwell, John W; Zimmerman, Peter A; Serre, David

    2015-03-01

    Significant insights into the biology of Plasmodium vivax have been gained from the ability to successfully adapt human infections to non-human primates. P. vivax strains grown in monkeys serve as a renewable source of parasites for in vitro and ex vivo experimental studies and functional assays, or for studying in vivo the relapse characteristics, mosquito species compatibilities, drug susceptibility profiles or immune responses towards potential vaccine candidates. Despite the importance of these studies, little is known as to how adaptation to a different host species may influence the genome of P. vivax. In addition, it is unclear whether these monkey-adapted strains consist of a single clonal population of parasites or if they retain the multiclonal complexity commonly observed in field isolates. Here we compare the genome sequences of seven P. vivax strains adapted to New World monkeys with those of six human clinical isolates collected directly in the field. We show that the adaptation of P. vivax parasites to monkey hosts, and their subsequent propagation, did not result in significant modifications of their genome sequence and that these monkey-adapted strains recapitulate the genomic diversity of field isolates. Our analyses also reveal that these strains are not always genetically homogeneous and should be analyzed cautiously. Overall, our study provides a framework to better leverage this important research material and fully utilize this resource for improving our understanding of P. vivax biology.

  15. Circulation of Campylobacter spp. in rhesus monkeys (Macaca mulatta held in captivity: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Ribeiro Andrade

    2007-02-01

    Full Text Available Campylobacteriosis is an extremely important zoonosis, circulating freely in the environment. In nonhuman primates kept in open facilities and bred for experimental purposes, the presence of Campylobacter spp. could cause severe damage to the production and interfere with the results of scientific research. In this paper, we assessed the circulation of Campylobacter spp. in a colony of clinically healthy rhesus monkeys (Macaca mulatta destined to research. The analysis was carried out during seven non-consecutive years. Data showed that despite several changes made in animal management along the studied years in order to control this zoonosis, reduction of bacterial charge did not occur. Significant differences among the age groups and sex were observed. Infants showed higher susceptibility than adult animals. In general males were more infected than females. Modifications adopted in the handling techniques need to be reviewed with the intent of improving the production, reducing bacterial infection of the stock and avoiding undesirable cross reactions in the research carried out with these animals. Therefore, this paper alerts professionals that work directly with captive rhesus monkeys about the risks of Campylobacter spp. infection and possible interference on the experimental procedures.

  16. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus

    International Nuclear Information System (INIS)

    Pletnev, Alexander G.; St Claire, Marisa; Elkins, Randy; Speicher, Jim; Murphy, Brian R.; Chanock, Robert M.

    2003-01-01

    Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3' noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3'Δ30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Δ30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3'Δ30, will be evaluated first in our initial clinical studies

  17. Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata

    Science.gov (United States)

    Diniz, Daniel G.; Silva, Geane O.; Naves, Thaís B.; Fernandes, Taiany N.; Araújo, Sanderson C.; Diniz, José A. P.; de Farias, Luis H. S.; Sosthenes, Marcia C. K.; Diniz, Cristovam G.; Anthony, Daniel C.; da Costa Vasconcelos, Pedro F.; Picanço Diniz, Cristovam W.

    2016-01-01

    It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous. PMID:27047345

  18. Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta)

    DEFF Research Database (Denmark)

    Bakker, J.; Thuesen, Line Risager; Braskamp, G.

    2011-01-01

    was to determine whether cefovecin is a suitable antibiotic to prevent skin wound infection in rhesus monkeys. Therefore, the pharmacokinetics (PK) of cefovecin after a single subcutaneous injection at 8 mg/kg bodyweight in four rhesus monkeys (Macaca mulatta) and sensitivity of bacterial isolates from fresh skin...... wounds were determined. After administration, blood, urine, and feces were collected, and concentrations of cefovecin were determined. Further, the minimum inhibitory concentrations (MIC) for bacteria isolated from fresh skin wounds of monkeys during a health control program were determined. The mean...... maximum plasma concentration (C(max) ) of cefovecin was 78 µg/mL and was achieved after 57 min. The mean apparent long elimination half-life (t½) was 6.6 h and excretion occurred mainly via urine. The MIC for the majority of the bacteria examined was >100 µg/mL. The PK of cefovecin in rhesus monkeys...

  19. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  20. Number of Grooming Partners Is Associated with Hookworm Infection in Wild Vervet Monkeys (Chlorocebus aethiops).

    Science.gov (United States)

    Wren, Brandi T; Remis, Melissa J; Camp, Joseph W; Gillespie, Thomas R

    2016-01-01

    There are many known benefits of social grooming among primates, including maintenance of social relationships, removal of ectoparasites, and improved physiological condition. Recently, however, researchers have noted that social grooming and social contact may also present a significant cost by facilitating transmission of some parasites and pathogens. We investigated whether the number of social grooming partners varied based on infection status for gastrointestinal parasites. We used focal animal sampling and continuous recording to collect data on the number of grooming partners for known individual vervet monkeys (Chlorocebus aethiops). We collected non-invasive faecal samples and examined them using faecal flotation, faecal sedimentation, and immunofluorescence microscopy. We detected 6 parasites: Trichuris sp. (92%), hookworm (71%), spirurids (68%), Oesophagostomum sp. (84%), Strongyloides sp. (24%), and Entamoeba coli (92%). The number of grooming partners varied significantly based on infection with hookworm and sex. No significant relationships were detected for other parasites. Associations between host behavioural variation and some parasite taxa (specifically Trichuris, Oesophagostomum, and Entamoeba spp.) were impossible to explore due to an extremely high prevalence among hosts. This is the first report that we are aware of that has detected an association between social grooming behaviours and infection with hookworm. © 2016 S. Karger AG, Basel.

  1. What Do Monkey Calls Mean?

    Science.gov (United States)

    Schlenker, Philippe; Chemla, Emmanuel; Zuberbühler, Klaus

    2016-12-01

    A field of primate linguistics is gradually emerging. It combines general questions and tools from theoretical linguistics with rich data gathered in experimental primatology. Analyses of several monkey systems have uncovered very simple morphological and syntactic rules and have led to the development of a primate semantics that asks new questions about the division of semantic labor between the literal meaning of monkey calls, additional mechanisms of pragmatic enrichment, and the environmental context. We show that comparative studies across species may validate this program and may in some cases help in reconstructing the evolution of monkey communication over millions of years. Copyright © 2016. Published by Elsevier Ltd.

  2. Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans.

    Directory of Open Access Journals (Sweden)

    Joy Gardner

    Full Text Available Chikungunya virus (CHIKV is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7-/- mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities.

  3. Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans.

    Directory of Open Access Journals (Sweden)

    Ilhem Messaoudi

    2009-11-01

    Full Text Available Simian varicella virus (SVV, the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV. Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation.

  4. On Loss Aversion in Capuchin Monkeys

    Science.gov (United States)

    Silberberg, Alan; Roma, Peter G.; Huntsberry, Mary E.; Warren-Boulton, Frederick R.; Sakagami, Takayuki; Ruggiero, Angela M.; Suomi, Stephen J.

    2008-01-01

    Chen, Lakshminarayanan, and Santos (2006) claim to show in three choice experiments that monkeys react rationally to price and wealth shocks, but, when faced with gambles, display hallmark, human-like biases that include loss aversion. We present three experiments with monkeys and humans consistent with a reinterpretation of their data that…

  5. Steroid metabolism by monkey and human spermatozoa

    International Nuclear Information System (INIS)

    Rajalakshmi, M.; Sehgal, A.; Pruthi, J.S.; Anand-Kumar, T.C.

    1983-01-01

    Freshly ejaculated spermatozoa from monkey and human were washed and incubated with tritium labelled androgens or estradiol to study the pattern of spermatozoa steroid metabolism. When equal concentrations of steroid substrates were used for incubation, monkey and human spermatozoa showed very similar pattern of steroid conversion. Spermatozoa from both species converted testosterone mainly to androstenedione, but reverse conversion of androstenedione to testosterone was negligible. Estradiol-17 beta was converted mainly to estrone. The close similarity between the spermatozoa of monkey and men in their steroid metabolic pattern indicates that the rhesus monkey could be an useful animal model to study the effect of drugs on the metabolic pattern of human spermatozoa

  6. Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon

    Directory of Open Access Journals (Sweden)

    Albert Lalremruata

    2015-09-01

    Interpretation: This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts.

  7. Antischistosomal activity of acridanone- hydrazones in Cebus monkeys experimentally infected with the SJ strain of Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Paulo Marcos Zech Coelho

    1995-09-01

    Full Text Available In this study, four compounds were utilized at the dose of 12.5mg/kg body weight, p.o., to treat Cebus monkeys experimentally infected with about 200 cercariae of Schistosoma mansoni (SJ strain, via transcutaneous route. The oograms performed with rectal snips, as well as stool examinations carried out periodically, showed no viable eggs of the parasite, from day 29 to 226post-treatment. The perfusion undertaken after killing the animals showed absence of worms in the treated monkeys, whereas 83 worms were recovered from the control, thus corroborating the results obtained by means of oograms and coproscopy. These results confirm the efficacy of 9-acridanone- hydrazones previously tested against the LE strain of S. mansoni. The low curative dose and apparent absence of toxicity render these dmgs an important therapeutic reserve, taking into consideration the reports on the resistance of S. mansoni to the modern drugs oxamniquine and praziquantel.No presente trabalho, quatro compostos foram utilizados na dose de 12,5mg/kg de peso, por via oral, em macacos infectados transcutaneamente com cerca de 200 cercárias de Schistosoma mansoni. Os oogramas realizados com fragmentos de mucosa retal e os exames de fezes realizados, periodicamente, demonstraram a ausência de ovos viáveis do parasito a partir do 29- até o 226a dia pós-tratamento. A perfusão, apôs sacrifício dos animais tratados, não detectou vermes, enquanto que do macaco cotztrole 83 vermes foram recuperados, confirmando assim os resultados dos oogramas e da coproscopia. Estes resultados confirmam a eficácia das 9-acridanonas- hydrazonas já observada anteriormente contra a cepa LE de S. mansoni. A baixa dosagem curativa e aparente ausência de toxicidade colocam estas drogas como uma reserva terapêutica importante, tendo em vista o relato de resistência do S. mansoni às drogas modernas oxamniquína e praziquantel.

  8. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  9. Safety, pharmacokinetic, and efficacy studies of oral DB868 in a first stage vervet monkey model of human African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    John K Thuita

    Full Text Available There are no oral drugs for human African trypanosomiasis (HAT, sleeping sickness. A successful oral drug would have the potential to reduce or eliminate the need for patient hospitalization, thus reducing healthcare costs of HAT. The development of oral medications is a key objective of the Consortium for Parasitic Drug Development (CPDD. In this study, we investigated the safety, pharmacokinetics, and efficacy of a new orally administered CPDD diamidine prodrug, 2,5-bis[5-(N-methoxyamidino-2-pyridyl]furan (DB868; CPD-007-10, in the vervet monkey model of first stage HAT. DB868 was well tolerated at a dose up to 30 mg/kg/day for 10 days, a cumulative dose of 300 mg/kg. Mean plasma levels of biomarkers indicative of liver injury (alanine aminotransferase, aspartate aminotransferase were not significantly altered by drug administration. In addition, no kidney-mediated alterations in creatinine and urea concentrations were detected. Pharmacokinetic analysis of plasma confirmed that DB868 was orally available and was converted to the active compound DB829 in both uninfected and infected monkeys. Treatment of infected monkeys with DB868 began 7 days post-infection. In the infected monkeys, DB829 attained a median C(max (dosing regimen that was 12-fold (3 mg/kg/day for 7 days, 15-fold (10 mg/kg/day for 7 days, and 31-fold (20 mg/kg/day for 5 days greater than the IC50 (14 nmol/L against T. b. rhodesiense STIB900. DB868 cured all infected monkeys, even at the lowest dose tested. In conclusion, oral DB868 cured monkeys with first stage HAT at a cumulative dose 14-fold lower than the maximum tolerated dose and should be considered a lead preclinical candidate in efforts to develop a safe, short course (5-7 days, oral regimen for first stage HAT.

  10. [Raman spectra of monkey cerebral cortex tissue].

    Science.gov (United States)

    Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

    2010-01-01

    Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

  11. Dissociation of item and source memory in rhesus monkeys.

    Science.gov (United States)

    Basile, Benjamin M; Hampton, Robert R

    2017-09-01

    Source memory, or memory for the context in which a memory was formed, is a defining characteristic of human episodic memory and source memory errors are a debilitating symptom of memory dysfunction. Evidence for source memory in nonhuman primates is sparse despite considerable evidence for other types of sophisticated memory and the practical need for good models of episodic memory in nonhuman primates. A previous study showed that rhesus monkeys confused the identity of a monkey they saw with a monkey they heard, but only after an extended memory delay. This suggests that they initially remembered the source - visual or auditory - of the information but forgot the source as time passed. Here, we present a monkey model of source memory that is based on this previous study. In each trial, monkeys studied two images, one that they simply viewed and touched and the other that they classified as a bird, fish, flower, or person. In a subsequent memory test, they were required to select the image from one source but avoid the other. With training, monkeys learned to suppress responding to images from the to-be-avoided source. After longer memory intervals, monkeys continued to show reliable item memory, discriminating studied images from distractors, but made many source memory errors. Monkeys discriminated source based on study method, not study order, providing preliminary evidence that our manipulation of retention interval caused errors due to source forgetting instead of source confusion. Finally, some monkeys learned to select remembered images from either source on cue, showing that they did indeed remember both items and both sources. This paradigm potentially provides a new model to study a critical aspect of episodic memory in nonhuman primates. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes' monkeys (Cercopithecus mitis in Kenya

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    Otsyula Moses G

    2004-10-01

    Full Text Available Abstract Background The Sykes' monkey and related forms (Cercopithecus mitis make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk. We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western blot assay and analyzed the data by origin, subspecies, age and sex. Results The SIVsyk antigen-specific Western blot assay detected more serum samples as positive than either of the cross-reactive ELISA assays. Using this assay, we found that seroprevalence is higher than previously reported, but extremely variable in wild populations (from 0.0 to 90.9%. Females were infected more often than males in both wild and captive populations. Seropositive infants were common. However, no seropositive juveniles were identified. Conclusion We have developed a specific and sensitive Western blot assay for anti-SIVsyk antibody detection. Sykes' monkeys are commonly infected with SIVsyk, but with extremely variable prevalence in the wild. Higher infection prevalence in females suggests predominantly sexual transmission. High infection prevalence in infants, but none in juveniles, suggests maternal antibodies, but little or no vertical transmission.

  13. Sex differences in rhesus monkey toy preferences parallel those of children

    Science.gov (United States)

    Hassett, Janice M.; Siebert, Erin R.; Wallen, Kim

    2008-01-01

    Socialization processes, parents, or peers encouraging play with gender specific toys are thought to be the primary force shaping sex differences in toy preference. A contrast in view is that toy preferences reflect biologically determined preferences for specific activities facilitated by specific toys. Sex differences in juvenile activities, such as rough and tumble play, peer preferences, and infant interest, share similarities in humans and monkeys. Thus if activity preferences shape toy preferences, male and female monkeys may show toy preferences similar to those seen in boys and girls. We compared the interactions of 34 rhesus monkeys, living within a 135 monkey troop, with human wheeled toys and plush toys. Male monkeys, like boys, showed consistent and strong preferences for wheeled toys, while female monkeys, like girls, showed greater variability in preferences. Thus, the magnitude of preference for wheeled over plush toys differed significantly between males and females. The similarities to human findings demonstrate that such preferences can develop without explicit gendered socialization. We offer the hypothesis that toy preferences reflect hormonally influenced behavioral and cognitive biases which are sculpted by social processes into the sex differences seen in monkeys and humans. PMID:18452921

  14. Hunted woolly monkeys (Lagothrix poeppigii show threat-sensitive responses to human presence.

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    Sarah Papworth

    Full Text Available Responding only to individuals of a predator species which display threatening behaviour allows prey species to minimise energy expenditure and other costs of predator avoidance, such as disruption of feeding. The threat sensitivity hypothesis predicts such behaviour in prey species. If hunted animals are unable to distinguish dangerous humans from non-dangerous humans, human hunting is likely to have a greater effect on prey populations as all human encounters should lead to predator avoidance, increasing stress and creating opportunity costs for exploited populations. We test the threat sensitivity hypothesis in wild Poeppigi's woolly monkeys (Lagothrix poeppigii in Yasuní National Park, Ecuador, by presenting human models engaging in one of three behaviours "hunting", "gathering" or "researching". These experiments were conducted at two sites with differing hunting pressures. Visibility, movement and vocalisations were recorded and results from two sites showed that groups changed their behaviours after being exposed to humans, and did so in different ways depending on the behaviour of the human model. Results at the site with higher hunting pressure were consistent with predictions based on the threat sensitivity hypothesis. Although results at the site with lower hunting pressure were not consistent with the results at the site with higher hunting pressure, groups at this site also showed differential responses to different human behaviours. These results provide evidence of threat-sensitive predator avoidance in hunted primates, which may allow them to conserve both time and energy when encountering humans which pose no threat.

  15. Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys.

    Science.gov (United States)

    Elliott, R B; Escobar, L; Calafiore, R; Basta, G; Garkavenko, O; Vasconcellos, A; Bambra, C

    2005-01-01

    Neonatal porcine islets within alginate microcapsules transplanted intraperitoneally (IP) or within semi-permeable macrocapsules (TheraCyte) and transplanted subcutaneously (SC) survive and reverse diabetes for up to 16 weeks in diabetic autoimmune nonobese diabetic (NOD) mice. The islets in microcapsules transplanted IP into nondiabetic cynomolgus monkeys survived for 8 weeks. Similar results were shown with islets transplanted in TheraCytes. Neither species showed adverse effects or evidence of infection with porcine endogenous retroviruses or other endemic pig viruses. Proof of principle is illustrated for successful xenotransplantation in humans.

  16. Nectin-4 Interactions Govern Measles Virus Virulence in a New Model of Pathogenesis, the Squirrel Monkey (Saimiri sciureus).

    Science.gov (United States)

    Delpeut, Sébastien; Sawatsky, Bevan; Wong, Xiao-Xiang; Frenzke, Marie; Cattaneo, Roberto; von Messling, Veronika

    2017-06-01

    In addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (MeV) infection. Disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain New World monkey species. To investigate if squirrel monkeys ( Saimiri sciureus ), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutics, we infected them with a green fluorescent protein-expressing MeV. Compared to cynomolgus macaques ( Macaca fascicularis ) infected with the same virus, the squirrel monkeys developed more-severe immunosuppression, higher viral load, and a broader range of clinical signs typical for measles. In contrast, infection with an MeV unable to interact with the epithelial receptor nectin-4, while causing immunosuppression, resulted in only a mild and transient rash and a short-lived elevation of the body temperature. Similar titers of the wild-type and nectin-4-blind MeV were detected in peripheral blood mononuclear cells and lymph node homogenates, but only the wild-type virus was found in tracheal lavage fluids and urine. Thus, our study demonstrates the importance of MeV interactions with nectin-4 for clinical disease in the new and better-performing S. sciureus model of measles pathogenesis. IMPORTANCE The characterization of mechanisms underlying measles virus clinical disease has been hampered by the lack of an animal model that reproduces the course of disease seen in human patients. Here, we report that infection of squirrel monkeys ( Saimiri sciureus ) fulfills these requirements. Comparative infection with wild-type and epithelial cell receptor-blind viruses demonstrated the importance of epithelial cell infection for clinical disease, highlighting the spread to epithelia as an attractive target for therapeutic strategies. Copyright © 2017 American Society for

  17. Depth perception from moving cast shadow in macaque monkey.

    Science.gov (United States)

    Mizutani, Saneyuki; Usui, Nobuo; Yokota, Takanori; Mizusawa, Hidehiro; Taira, Masato; Katsuyama, Narumi

    2015-07-15

    In the present study, we investigate whether the macaque monkey can perceive motion in depth using a moving cast shadow. To accomplish this, we conducted two experiments. In the first experiment, an adult Japanese monkey was trained in a motion discrimination task in depth by binocular disparity. A square was presented on the display so that it appeared with a binocular disparity of 0.12 degrees (initial position), and moved toward (approaching) or away from (receding) the monkey for 1s. The monkey was trained to discriminate the approaching and receding motion of the square by GO/delayed GO-type responses. The monkey showed a significantly high accuracy rate in the task, and the performance was maintained when the position, color, and shape of the moving object were changed. In the next experiment, the change in the disparity was gradually decreased in the motion discrimination task. The results showed that the performance of the monkey declined as the distance of the approaching and receding motion of the square decreased from the initial position. However, when a moving cast shadow was added to the stimulus, the monkey responded to the motion in depth induced by the cast shadow in the same way as by binocular disparity; the reward was delivered randomly or given in all trials to prevent the learning of the 2D motion of the shadow in the frontal plane. These results suggest that the macaque monkey can perceive motion in depth using a moving cast shadow as well as using binocular disparity. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. PENGARUH PERSEPSI EKOWISATA TERHADAP TINGKAT KEPUASAN WISATAWAN DI MONKEY FOREST UBUD, BALI

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    Via Reza Efrida

    2017-07-01

    Full Text Available This study aims to investigate (1 the ecotourism perception of tourists visiting Monkey Forest Ubud; (2 the visitor satisfaction level on Monkey Forest Ubud attraction; and (3 the influence of ecotourism perception on visitor satisfaction level at Monkey Forest Ubud. The result of this research carried out descriptive statistic by using an importance-performance analysis (IPA and inferential statistic by using a simple linear regression analysis. The technique of determining sample size is incidental sampling technique by distributing questionnaires to 170 tourists visiting Monkey Forest Ubud. The result showed that tourists which visit Monkey Forest Ubud strongly agree on the implementation of ecotourism concept. On the other hand, the calculation results of concordance rate showed 89.59% which means that the overall tourist is satisfied with the Monkey Forest Ubud attraction. Moreover, based on the hypothesis testing by using t-test statistical significance showed that there is a significant influence of independent variable (perception of ecotourism on the dependent variable (tourist satisfaction.

  19. High Leptospira seroprevalence in captive and wild-caught vervet monkeys ( Chlorocebus sabeus) on the Caribbean island of Saint Kitts.

    Science.gov (United States)

    Rajeev, Sreekumari; Conan, Anne; Pratt, Nicola; Beierschmitt, Amy; Palmour, Roberta

    2017-11-01

    Leptospirosis is a zoonotic disease of global importance. Very little information is available on Leptospira infection in nonhuman primates. We report herein a high seroprevalence (49.4%; 95% confidence interval: 41.6-57.2%) to Leptospira serovars in vervet monkeys ( Chlorocebus sabeus) on the Caribbean island of Saint Kitts. Monkeys bred in captivity ( n = 81) had a significantly higher seroprevalence compared to wild-caught monkeys ( n = 81; p Leptospira serovars and seroconversion occurs in wild and captive vervet monkeys on the Caribbean island of Saint Kitts. Further studies are warranted to better understand epidemiology, transmission, pathology, and possible reservoir status in this species.

  20. Photodynamic treatment of Herpes simplex virus infection in vitro

    International Nuclear Information System (INIS)

    Lytle, C.D.; Hester, L.D.

    1976-01-01

    The effects of photodynamic action on in vitro herpes simplex virus infections of CV-1 monkey kidney fibroblasts or human skin fibroblasts were determined using proflavine sulfate and white fluorescent lamps. Photodynamic treatment of confluent cell monolayers prior to virus infection inactivated cell capacity, i.e. the capacity of the treated cells to support subsequent virus growth as measured by plaque formation. The capacity of human cells was more sensitive to inactivation than the capacity of monkey cells when 6 μM proflavine was used. Treated cell monolayers recovered the capacity to support virus plaque formation when virus infection was delayed four days after the treatment. Experiments in which the photodynamically treated monolayers were infected with UV-irradiated virus demonstrated that this treatment induced Weigle reactivation in both types of cells. This reactivation occurred for virus infection just after treatment or 4 days later. A Luria-Latarjet-type experiment was also performed in which cultures infected with unirradiated virus were photodynamically treated at different times after the start of infection. The results showed that for the first several hours of the virus infection the infected cultures were more sensitive to inactivation by photodynamic treatment than cell capacity. By the end of the eclipse period the infected cultures were less sensitive to inactivation than cell capacity. Results from extracellular inactivation of virus growth in monkey cells at 6 μM proflavine indicated that at physiological pH the virus has a sensitivity to photodynamic inactivation similar to that for inactivation of cell capacity. The combined data indicated that photodynamic treatment of the cell before or after virus infection could prevent virus growth. Thus, photodynamic inactivation of infected and uninfected cells may be as important as inactivation of virus particles when considering possible mechanisms in clinical photodynamic therapy for herpes

  1. The Role of the Antiviral APOBEC3 Gene Family in Protecting Chimpanzees against Lentiviruses from Monkeys.

    Directory of Open Access Journals (Sweden)

    Lucie Etienne

    2015-09-01

    Full Text Available Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee's main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4(+ T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses.

  2. Plasmodium knowlesi Skeleton-Binding Protein 1 Localizes to the 'Sinton and Mulligan' Stipplings in the Cytoplasm of Monkey and Human Erythrocytes.

    Science.gov (United States)

    Lucky, Amuza Byaruhanga; Sakaguchi, Miako; Katakai, Yuko; Kawai, Satoru; Yahata, Kazuhide; Templeton, Thomas J; Kaneko, Osamu

    2016-01-01

    The malaria parasite, Plasmodium, exports protein products to the infected erythrocyte to introduce modifications necessary for the establishment of nutrient acquisition and surface display of host interaction ligands. Erythrocyte remodeling impacts parasite virulence and disease pathology and is well documented for the human malaria parasite Plasmodium falciparum, but has been less described for other Plasmodium species. For P. falciparum, the exported protein skeleton-binding protein 1 (PfSBP1) is involved in the trafficking of erythrocyte surface ligands and localized to membranous structures within the infected erythrocyte, termed Maurer's clefts. In this study, we analyzed SBP1 orthologs across the Plasmodium genus by BLAST analysis and conserved gene synteny, which were also recently described by de Niz et al. (2016). To evaluate the localization of an SBP1 ortholog, we utilized the zoonotic malaria parasite, Plasmodium knowlesi. Immunofluorescence assay of transgenic P. knowlesi parasites expressing epitope-tagged recombinant PkSBP1 revealed a punctate staining pattern reminiscent of Maurer's clefts, following infection of either monkey or human erythrocytes. The recombinant PkSBP1-positive puncta co-localized with Giemsa-stained structures, known as 'Sinton and Mulligan' stipplings. Immunoelectron microscopy also showed that recombinant PkSBP1 localizes within or on the membranous structures akin to the Maurer's clefts. The recombinant PkSBP1 expressed in P. falciparum-infected erythrocytes co-localized with PfSBP1 at the Maurer's clefts, indicating an analogous trafficking pattern. A member of the P. knowlesi 2TM protein family was also expressed and localized to membranous structures in infected monkey erythrocytes. These results suggest that the trafficking machinery and induced erythrocyte cellular structures of P. knowlesi are similar following infection of both monkey and human erythrocytes, and are conserved with P. falciparum.

  3. Monkey Viperin Restricts Porcine Reproductive and Respiratory Syndrome Virus Replication.

    Science.gov (United States)

    Fang, Jianyu; Wang, Haiyan; Bai, Juan; Zhang, Qiaoya; Li, Yufeng; Liu, Fei; Jiang, Ping

    2016-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen which causes huge economic damage globally in the swine industry. Current vaccination strategies provide only limited protection against PRRSV infection. Viperin is an interferon (IFN) stimulated protein that inhibits some virus infections via IFN-dependent or IFN-independent pathways. However, the role of viperin in PRRSV infection is not well understood. In this study, we cloned the full-length monkey viperin (mViperin) complementary DNA (cDNA) from IFN-α-treated African green monkey Marc-145 cells. It was found that the mViperin is up-regulated following PRRSV infection in Marc-145 cells along with elevated IRF-1 gene levels. IFN-α induced mViperin expression in a dose- and time-dependent manner and strongly inhibits PRRSV replication in Marc-145 cells. Overexpression of mViperin suppresses PRRSV replication by blocking the early steps of PRRSV entry and genome replication and translation but not inhibiting assembly and release. And mViperin co-localized with PRRSV GP5 and N protein, but only interacted with N protein in distinct cytoplasmic loci. Furthermore, it was found that the 13-16 amino acids of mViperin were essential for inhibiting PRRSV replication, by disrupting the distribution of mViperin protein from the granular distribution to a homogeneous distribution in the cytoplasm. These results could be helpful in the future development of novel antiviral therapies against PRRSV infection.

  4. Comparative imaging study on monkeys with hemi-parkinsonism

    International Nuclear Information System (INIS)

    Wang Wei; Yu Xiaoping; Mao Jun; Liu Sheng; Wang Xiaoyi; Peng Guangchun; Wang Ruiwen

    2003-01-01

    Objective: To study the imaging appearance of experimental Parkinson's disease (PD) and to evaluate the different medical imaging exams on PD. Methods: CT, MRI, SPECT (dopamine transporter imaging and regional cerebral blood flow imaging, DAT imaging and rCBF imaging), and PET (glucose metabolism imaging) were performed on 8 monkeys before and after the infusion of MPTP into unilateral internal carotid artery to develop hemi-Parkinsonism models. Results: Hemi-Parkinsonism models were successfully induced on all 8 monkeys. On DAT imaging, the uptake values of the lesioned striatums decreased obviously after the MPTP treatment and were lower than that of the contralateral ones. The glucose metabolic rates of the lesioned striatums and thalamus in PD models were lower, compared to that of the healthy monkeys and that of the contralateral sides of themselves. Neither DAT nor glucose metabolism abnormalities was found on both the contralateral sides of the healthy and PD monkeys. On MRI images before MPTP treatment, only 4 of 8 PD models showed hypointense in bilateral globus pallidus. No abnormal MRI findings occurred in the first 2 months after injection of MPTP. At tile third month, hypointense appeared in globus pallidus of three monkeys. Enlarged hyposignal region in globus pallidus were found in three models. Of the above 6 monkeys, two appeared hypointense in putamina. Substantia nigra demonstrated no abnormalities before and after MPTP treatment. All rCBF and CT images were normal. Conclusion: The decreased density of DAT and decreased glucose metabolism on experimental PD can be showed early by DAT imaging and glucose metabolism imaging, MRI can show abnormal signal in the basal ganglia of PD but it is later than DAT and glucose metabolism imaging. CT and rCBF find no abnormality on PD

  5. Dissecting the mechanisms of squirrel monkey (Saimiri boliviensis) social learning.

    Science.gov (United States)

    Hopper, Lm; Holmes, An; Williams, LE; Brosnan, Sf

    2013-01-01

    Although the social learning abilities of monkeys have been well documented, this research has only focused on a few species. Furthermore, of those that also incorporated dissections of social learning mechanisms, the majority studied either capuchins (Cebus apella) or marmosets (Callithrix jacchus). To gain a broader understanding of how monkeys gain new skills, we tested squirrel monkeys (Saimiri boliviensis) which have never been studied in tests of social learning mechanisms. To determine whether S. boliviensis can socially learn, we ran "open diffusion" tests with monkeys housed in two social groups (N = 23). Over the course of 10 20-min sessions, the monkeys in each group observed a trained group member retrieving a mealworm from a bidirectional task (the "Slide-box"). Two thirds (67%) of these monkeys both learned how to operate the Slide-box and they also moved the door significantly more times in the direction modeled by the trained demonstrator than the alternative direction. To tease apart the underlying social learning mechanisms we ran a series of three control conditions with 35 squirrel monkeys that had no previous experience with the Slide-box. The first replicated the experimental open diffusion sessions but without the inclusion of a trained model, the second was a no-information control with dyads of monkeys, and the third was a 'ghost' display shown to individual monkeys. The first two controls tested for the importance of social support (mere presence effect) and the ghost display showed the affordances of the task to the monkeys. The monkeys showed a certain level of success in the group control (54% of subjects solved the task on one or more occasions) and paired controls (28% were successful) but none were successful in the ghost control. We propose that the squirrel monkeys' learning, observed in the experimental open diffusion tests, can be best described by a combination of social learning mechanisms in concert; in this case, those

  6. Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations.

    Science.gov (United States)

    Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

    2014-06-01

    Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 10(8) , 2 × 10(9) and 2 × 10(10) colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 10(9) CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 10(10) CFU). The challenge dose, 2 × 10(10) CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. © 2013 The Authors. APMIS published by John Wiley & Sons Ltd.

  7. Rhesus monkeys (Macaca mulatta) show robust primacy and recency in memory for lists from small, but not large, image sets.

    Science.gov (United States)

    Basile, Benjamin M; Hampton, Robert R

    2010-02-01

    The combination of primacy and recency produces a U-shaped serial position curve typical of memory for lists. In humans, primacy is often thought to result from rehearsal, but there is little evidence for rehearsal in nonhumans. To further evaluate the possibility that rehearsal contributes to primacy in monkeys, we compared memory for lists of familiar stimuli (which may be easier to rehearse) to memory for unfamiliar stimuli (which are likely difficult to rehearse). Six rhesus monkeys saw lists of five images drawn from either large, medium, or small image sets. After presentation of each list, memory for one item was assessed using a serial probe recognition test. Across four experiments, we found robust primacy and recency with lists drawn from small and medium, but not large, image sets. This finding is consistent with the idea that familiar items are easier to rehearse and that rehearsal contributes to primacy, warranting further study of the possibility of rehearsal in monkeys. However, alternative interpretations are also viable and are discussed. Copyright 2009 Elsevier B.V. All rights reserved.

  8. Plasmodium knowlesi Skeleton-Binding Protein 1 Localizes to the ‘Sinton and Mulligan’ Stipplings in the Cytoplasm of Monkey and Human Erythrocytes

    Science.gov (United States)

    Lucky, Amuza Byaruhanga; Sakaguchi, Miako; Katakai, Yuko; Kawai, Satoru; Yahata, Kazuhide; Templeton, Thomas J.

    2016-01-01

    The malaria parasite, Plasmodium, exports protein products to the infected erythrocyte to introduce modifications necessary for the establishment of nutrient acquisition and surface display of host interaction ligands. Erythrocyte remodeling impacts parasite virulence and disease pathology and is well documented for the human malaria parasite Plasmodium falciparum, but has been less described for other Plasmodium species. For P. falciparum, the exported protein skeleton-binding protein 1 (PfSBP1) is involved in the trafficking of erythrocyte surface ligands and localized to membranous structures within the infected erythrocyte, termed Maurer's clefts. In this study, we analyzed SBP1 orthologs across the Plasmodium genus by BLAST analysis and conserved gene synteny, which were also recently described by de Niz et al. (2016). To evaluate the localization of an SBP1 ortholog, we utilized the zoonotic malaria parasite, Plasmodium knowlesi. Immunofluorescence assay of transgenic P. knowlesi parasites expressing epitope-tagged recombinant PkSBP1 revealed a punctate staining pattern reminiscent of Maurer's clefts, following infection of either monkey or human erythrocytes. The recombinant PkSBP1-positive puncta co-localized with Giemsa-stained structures, known as ‘Sinton and Mulligan’ stipplings. Immunoelectron microscopy also showed that recombinant PkSBP1 localizes within or on the membranous structures akin to the Maurer's clefts. The recombinant PkSBP1 expressed in P. falciparum-infected erythrocytes co-localized with PfSBP1 at the Maurer's clefts, indicating an analogous trafficking pattern. A member of the P. knowlesi 2TM protein family was also expressed and localized to membranous structures in infected monkey erythrocytes. These results suggest that the trafficking machinery and induced erythrocyte cellular structures of P. knowlesi are similar following infection of both monkey and human erythrocytes, and are conserved with P. falciparum. PMID:27732628

  9. Genome Editing of Monkey.

    Science.gov (United States)

    Liu, Zhen; Cai, Yijun; Sun, Qiang

    2017-01-01

    Gene-modified monkey models would be particularly valuable in biomedical and neuroscience research. Virus-based transgenic and programmable nucleases-based site-specific gene editing methods (TALEN, CRISPR-cas9) enable the generation of gene-modified monkeys with gain or loss of function of specific genes. Here, we describe the generation of transgenic and knock-out (KO) monkeys with high efficiency by lentivirus and programmable nucleases.

  10. Spider monkey, Muriqui and Woolly monkey relationships revisited.

    Science.gov (United States)

    de Lima, Margarida Maria Celeira; Sampaio, Iracilda; Vieira, Ricardo dos Santos; Schneider, Horacio

    2007-01-01

    The taxonomic relationships among the four genera of the Atelidae family, Alouatta (Howler), Ateles (Spider), Lagothrix (Woolly) and Brachyteles (Muriqui), have been the subject of great debate. In general, almost all authors agree with the assignment of Howler monkeys as the basal genus, either in its own tribe Alouattini or in the subfamily Alouattinae, but they disagree on the associations among the other members of the family. Muriquis have been grouped with Spider monkeys based on the fact that they share various behavioral and morphological characteristics. Cladistic analyses using morphological, biochemical, karyotype and behavioral characteristics depicted a phylogenetic tree that places Howler as the basal genus and the remaining genera in an unresolved politomy. More recent studies using molecular data have suggested that Muriqui and Woolly monkeys are sister groups. However, a recent study based on nuclear and mtDNA argued that politomy is what best represents the relationships among Spider, Woolly and Muriqui. To contribute to this debate we have added new data from two nuclear genes, Transferrin and von Willebrand Factor, and using an alignment of 17,997 bp we demonstrate that a total analysis strongly supports the Muriqui-Woolly clade. A gene-to-gene approach showed that four of the eight nuclear genes provide support for the Muriqui-Woolly clade, two strongly and two moderately, while none of the eight genes provide support for any alternative arrangement. The mitochondrial genes were not able to resolve the politomy. A possible reason for the difficulty in resolving atelid relationships may be the short period of time separating each cladogenetic event in the evolutionary process that shaped this family.

  11. Newly Identified CYP2C93 Is a Functional Enzyme in Rhesus Monkey, but Not in Cynomolgus Monkey

    OpenAIRE

    Uno, Yasuhiro; Uehara, Shotaro; Kohara, Sakae; Iwasaki, Kazuhide; Nagata, Ryoichi; Fukuzaki, Koichiro; Utoh, Masahiro; Murayama, Norie; Yamazaki, Hiroshi

    2011-01-01

    Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP) 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C9...

  12. Comparison of Object Recognition Behavior in Human and Monkey

    Science.gov (United States)

    Rajalingham, Rishi; Schmidt, Kailyn

    2015-01-01

    Although the rhesus monkey is used widely as an animal model of human visual processing, it is not known whether invariant visual object recognition behavior is quantitatively comparable across monkeys and humans. To address this question, we systematically compared the core object recognition behavior of two monkeys with that of human subjects. To test true object recognition behavior (rather than image matching), we generated several thousand naturalistic synthetic images of 24 basic-level objects with high variation in viewing parameters and image background. Monkeys were trained to perform binary object recognition tasks on a match-to-sample paradigm. Data from 605 human subjects performing the same tasks on Mechanical Turk were aggregated to characterize “pooled human” object recognition behavior, as well as 33 separate Mechanical Turk subjects to characterize individual human subject behavior. Our results show that monkeys learn each new object in a few days, after which they not only match mean human performance but show a pattern of object confusion that is highly correlated with pooled human confusion patterns and is statistically indistinguishable from individual human subjects. Importantly, this shared human and monkey pattern of 3D object confusion is not shared with low-level visual representations (pixels, V1+; models of the retina and primary visual cortex) but is shared with a state-of-the-art computer vision feature representation. Together, these results are consistent with the hypothesis that rhesus monkeys and humans share a common neural shape representation that directly supports object perception. SIGNIFICANCE STATEMENT To date, several mammalian species have shown promise as animal models for studying the neural mechanisms underlying high-level visual processing in humans. In light of this diversity, making tight comparisons between nonhuman and human primates is particularly critical in determining the best use of nonhuman primates to

  13. Wave aberrations in rhesus monkeys with vision-induced ametropias

    Science.gov (United States)

    Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Huang, Juan; Roorda, Austin; Smith, Earl L.

    2007-01-01

    The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development. PMID:17825347

  14. Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes' monkeys (Cercopithecus mitis) in Kenya

    OpenAIRE

    Otsyula Moses G; Robinson James; Elliott Debra; Munene Elephas; Ellis Brett R; Michael Scott F

    2004-01-01

    Abstract Background The Sykes' monkey and related forms (Cercopithecus mitis) make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk). We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western...

  15. Cup tool use by squirrel monkeys.

    Science.gov (United States)

    Buckmaster, Christine L; Hyde, Shellie A; Parker, Karen J; Lyons, David M

    2015-12-01

    Captive-born male and female squirrel monkeys spontaneously 'invented' a cup tool use technique to Contain (i.e., hold and control) food they reduced into fragments for consumption and to Contain water collected from a valve to drink. Food cup use was observed more frequently than water cup use. Observations indicate that 68% (n = 39/57) of monkeys in this population used a cup (a plastic slip cap) to Contain food, and a subset of these monkeys, 10% (n = 4/39), also used a cup to Contain water. Cup use was optional and did not replace, but supplemented, the hand/arm-to-mouth eating and direct valve drinking exhibited by all members of the population. Strategies monkeys used to bring food and cups together for food processing activity at preferred upper-level perching areas, in the arboreal-like environment in which they lived, provides evidence that monkeys may plan food processing activity with the cups. Specifically, prior to cup use monkeys obtained a cup first before food, or obtained food and a cup from the floor simultaneously, before transporting both items to upper-level perching areas. After food processing activity with cups monkeys rarely dropped the cups and more often placed the cups onto perching. Monkeys subsequently returned to use cups that they previously placed on perching after food processing activity. The latter behavior is consistent with the possibility that monkeys may keep cups at preferred perching sites for future food processing activity and merits experimental investigation. Reports of spontaneous tool use by squirrel monkeys are rare and this is the first report of population-level tool use. These findings offer insights into the cognitive abilities of squirrel monkeys and provide a new context for behavior studies with this genus and for comparative studies with other primates. © 2015 Wiley Periodicals, Inc.

  16. Assessment of the Duration of Protection in Campylobacter jejuni Experimental Infection in Humans

    Science.gov (United States)

    2010-01-01

    of inoculum delivery was based on evidence obtained with a human Shigella infection model, which showed that 11/12 (92%) nai’ve subjects developed...M. Reyes, M. Salazar, R. Mezn, C. K. l’orter, and S. E. Walz. 2006. Ncw World monkey Aotus nmrc:ymat: as a model for Campyloba,·ter jejuni infection

  17. Change detection by rhesus monkeys (Macaca mulatta) and pigeons (Columba livia).

    Science.gov (United States)

    Elmore, L Caitlin; Magnotti, John F; Katz, Jeffrey S; Wright, Anthony A

    2012-08-01

    Two monkeys (Macaca mulatta) learned a color change-detection task where two colored circles (selected from a 4-color set) were presented on a 4 × 4 invisible matrix. Following a delay, the correct response was to touch the changed colored circle. The monkeys' learning, color transfer, and delay transfer were compared to a similar experiment with pigeons. Monkeys, like pigeons (Columba livia), showed full transfer to four novel colors, and to delays as long as 6.4 s, suggesting they remembered the colors as opposed to perceptual based attentional capture process that may work at very short delays. The monkeys and pigeons were further tested to compare transfer with other dimensions. Monkeys transferred to shape and location changes, unlike the pigeons, but neither species transferred to size changes. Thus, monkeys were less restricted in their domain to detect change than pigeons, but both species learned the basic task and appear suitable for comparative studies of visual short-term memory. 2012 APA, all rights reserved

  18. Control of Working Memory in Rhesus Monkeys (Macaca mulatta)

    Science.gov (United States)

    Tu, Hsiao-Wei; Hampton, Robert R.

    2014-01-01

    Cognitive control is critical for efficiently using the limited resources in working memory. It is well established that humans use rehearsal to increase the probability of remembering needed information, but little is known in nonhumans, with some studies reporting the absence of active control and others subject to alternative explanations. We trained monkeys in a visual matching-to-sample paradigm with a post-sample memory cue. Monkeys either saw a remember cue that predicted the occurrence of a matching test that required memory for the sample, or a forget cue that predicted a discrimination test that did not require memory of the sample. Infrequent probe trials on which monkeys were given tests of the type not cued on that trial were used to assess whether memory was under cognitive control. Our procedures controlled for reward expectation and for the surprising nature of the probes. Monkeys matched less accurately after forget cues, while discrimination accuracy was equivalent in the two cue conditions. We also tested monkeys with lists of two consecutive sample images that shared the same cue. Again, memory for expected memory tests was superior to that on unexpected tests. Together these results show that monkeys cognitively control their working memory. PMID:25436219

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA protein in a human immunodeficiency virus type 1 (HIV-1 derivative that has simian immunodeficiency virus (SIVmac239 vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

    Directory of Open Access Journals (Sweden)

    Adachi Akio

    2009-08-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5 of capsid protein (CA and the entire SIVmac239 vif gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7 of HIV type 2 (HIV-2 CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α. Results In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and vif with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells. Conclusion We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys in vivo.

  1. Responses of squirrel monkeys to their experimentally modified mobbing calls

    Science.gov (United States)

    Fichtel, Claudia; Hammerschmidt, Kurt

    2003-05-01

    Previous acoustic analyses suggested emotion-correlated changes in the acoustic structure of squirrel monkey (Saimiri sciureus) vocalizations. Specifically, calls given in aversive contexts were characterized by an upward shift in frequencies, often accompanied by an increase in amplitude. In order to test whether changes in frequencies or amplitude are indeed relevant for conspecific listeners, playback experiments were conducted in which either frequencies or amplitude of mobbing calls were modified. Latency and first orienting response were measured in playback experiments with six adult squirrel monkeys. After broadcasting yaps with increased frequencies or amplitude, squirrel monkeys showed a longer orienting response towards the speaker than after the corresponding control stimuli. Furthermore, after broadcasting yaps with decreased frequencies or amplitude, squirrel monkeys showed a shorter orienting response towards the speaker than after the corresponding manipulated calls with higher frequencies or amplitude. These results suggest that changes in frequencies or amplitude were perceived by squirrel monkeys, indicating that the relationship between call structure and the underlying affective state of the caller agreed with the listener's assessment of the calls. However, a simultaneous increase in frequencies and amplitude did not lead to an enhanced response, compared to each single parameter. Thus, from the receiver's perspective, both call parameters may mutually replace each other.

  2. Long term lung clearance and cellular retention of cadmium in rats and monkeys

    International Nuclear Information System (INIS)

    Oberdorster, G.; Cox, C.; Baggs, R.

    1987-01-01

    The paper describes experiments to determine the long term lung clearance and cellular retention of cadmium in rats and monkeys. The rats and monkeys were exposed to 109 Cd Cl 2 aerosols, and one monkey was exposed to 115 CdO particles. The thoracic activity of the respective Cd isotopes was measured with time after exposure, for both species. Accumulation of 109 Cd in the kidneys of the monkeys exposed to 109 Cd Cl 2 was also examined, and autoradiographs of lung sections of these monkeys were also prepared. The results showed that the cadmium accumulated differently in the lungs of the rats and primates. (U.K.)

  3. 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.

  4. Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

    OpenAIRE

    Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

    2017-01-01

    Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blo...

  5. Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images.

    Science.gov (United States)

    Chang, Liangtang; Zhang, Shikun; Poo, Mu-Ming; Gong, Neng

    2017-03-21

    Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal.

  6. Formal monkey linguistics : The debate

    NARCIS (Netherlands)

    Schlenker, Philippe; Chemla, Emmanuel; Schel, Anne M.|info:eu-repo/dai/nl/413333450; Fuller, James; Gautier, Jean Pierre; Kuhn, Jeremy; Veselinović, Dunja; Arnold, Kate; Cäsar, Cristiane; Keenan, Sumir; Lemasson, Alban; Ouattara, Karim; Ryder, Robin; Zuberbühler, Klaus

    2016-01-01

    We explain why general techniques from formal linguistics can and should be applied to the analysis of monkey communication - in the areas of syntax and especially semantics. An informed look at our recent proposals shows that such techniques needn't rely excessively on categories of human language:

  7. Performance norms for a rhesus monkey neuropsychological testing battery: acquisition and long-term performance.

    Science.gov (United States)

    Weed, M R; Taffe, M A; Polis, I; Roberts, A C; Robbins, T W; Koob, G F; Bloom, F E; Gold, L H

    1999-10-25

    A computerized behavioral battery based upon human neuropsychological tests (CANTAB, CeNeS, Cambridge, UK) has been developed to assess cognitive behaviors of rhesus monkeys. Monkeys reliably performed multiple tasks, providing long-term assessment of changes in a number of behaviors for a given animal. The overall goal of the test battery is to characterize changes in cognitive behaviors following central nervous system (CNS) manipulations. The battery addresses memory (delayed non-matching to sample, DNMS; spatial working memory, using a self-ordered spatial search task, SOSS), attention (intra-/extra-dimensional shift, ID/ED), motivation (progressive-ratio, PR), reaction time (RT) and motor coordination (bimanual task). As with human neuropsychological batteries, different tasks are thought to involve different neural substrates, and therefore performance profiles should assess function in particular brain regions. Monkeys were tested in transport cages, and responding on a touch sensitive computer monitor was maintained by food reinforcement. Parametric manipulations of several tasks demonstrated the sensitivity of performance to increases in task difficulty. Furthermore, the factors influencing difficulty for rhesus monkeys were the same as those shown to affect human performance. Data from this study represent performance of a population of healthy normal monkeys that will be used for comparison in subsequent studies of performance following CNS manipulations such as infection with simian immunodeficiency virus (NeuroAIDS) or drug administration.

  8. Detailed analysis of the African green monkey model of Nipah virus disease.

    Directory of Open Access Journals (Sweden)

    Sara C Johnston

    Full Text Available Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5 × 10(4 plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.

  9. Rhesus monkeys see who they hear: spontaneous cross-modal memory for familiar conspecifics.

    Directory of Open Access Journals (Sweden)

    Ikuma Adachi

    Full Text Available Rhesus monkeys gather much of their knowledge of the social world through visual input and may preferentially represent this knowledge in the visual modality. Recognition of familiar faces is clearly advantageous, and the flexibility and utility of primate social memory would be greatly enhanced if visual memories could be accessed cross-modally either by visual or auditory stimulation. Such cross-modal access to visual memory would facilitate flexible retrieval of the knowledge necessary for adaptive social behavior. We tested whether rhesus monkeys have cross-modal access to visual memory for familiar conspecifics using a delayed matching-to-sample procedure. Monkeys learned visual matching of video clips of familiar individuals to photographs of those individuals, and generalized performance to novel videos. In crossmodal probe trials, coo-calls were played during the memory interval. The calls were either from the monkey just seen in the sample video clip or from a different familiar monkey. Even though the monkeys were trained exclusively in visual matching, the calls influenced choice by causing an increase in the proportion of errors to the picture of the monkey whose voice was heard on incongruent trials. This result demonstrates spontaneous cross-modal recognition. It also shows that viewing videos of familiar monkeys activates naturally formed memories of real monkeys, validating the use of video stimuli in studies of social cognition in monkeys.

  10. Vicarious learning from human models in monkeys.

    Science.gov (United States)

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  11. Do you see what I see? A comparative investigation of the Delboeuf illusion in humans (Homo sapiens), rhesus monkeys (Macaca mulatta), and capuchin monkeys (Cebus apella).

    Science.gov (United States)

    Parrish, Audrey E; Brosnan, Sarah F; Beran, Michael J

    2015-10-01

    Studying visual illusions is critical to understanding typical visual perception. We investigated whether rhesus monkeys (Macaca mulatta) and capuchin monkeys (Cebus apella) perceived the Delboeuf illusion in a similar manner as human adults (Homo sapiens). To test this, in Experiment 1, we presented monkeys and humans with a relative discrimination task that required subjects to choose the larger of 2 central dots that were sometimes encircled by concentric rings. As predicted, humans demonstrated evidence of the Delboeuf illusion, overestimating central dots when small rings surrounded them and underestimating the size of central dots when large rings surrounded them. However, monkeys did not show evidence of the illusion. To rule out an alternate explanation, in Experiment 2, we presented all species with an absolute classification task that required them to classify a central dot as "small" or "large." We presented a range of ring sizes to determine whether the Delboeuf illusion would occur for any dot-to-ring ratios. Here, we found evidence of the Delboeuf illusion in all 3 species. Humans and monkeys underestimated central dot size to a progressively greater degree with progressively larger rings. The Delboeuf illusion now has been extended to include capuchin monkeys and rhesus monkeys, and through such comparative investigations we can better evaluate hypotheses regarding illusion perception among nonhuman animals. (c) 2015 APA, all rights reserved).

  12. Newly identified CYP2C93 is a functional enzyme in rhesus monkey, but not in cynomolgus monkey.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Uno

    Full Text Available Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C93 cDNA contained an open reading frame of 490 amino acids approximately 84-86% identical to human CYP2Cs. CYP2C93 was located in the genomic region, which corresponded to the intergenic region in the human genome, indicating that CYP2C93 does not correspond to any human genes. CYP2C93 mRNA was expressed predominantly in the liver among 10 tissues analyzed. The CYP2C93 proteins heterologously expressed in Escherichia coli metabolized human CYP2C substrates, diclofenac, flurbiprofen, paclitaxel, S-mephenytoin, and tolbutamide. In addition to a normal transcript (SV1, an aberrantly spliced transcript (SV2 lacking exon 2 was identified, which did not give rise to a functional protein due to frameshift and a premature termination codon. Mini gene assay revealed that the genetic variant IVS2-1G>T at the splice site of intron 1, at least partly, accounted for the exon-2 skipping; therefore, this genotype would influence CYP2C93-mediated drug metabolism. SV1 was expressed in 6 of 11 rhesus monkeys and 1 of 8 cynomolgus monkeys, but the SV1 in the cynomolgus monkey was nonfunctional due to a rare null genotype (c.102T>del. These results suggest that CYP2C93 can play roles as a drug-metabolizing enzyme in rhesus monkeys (not in cynomolgus monkeys, although its relative contribution to drug metabolism has yet to be validated.

  13. Basic math in monkeys and college students.

    Science.gov (United States)

    Cantlon, Jessica F; Brannon, Elizabeth M

    2007-12-01

    Adult humans possess a sophisticated repertoire of mathematical faculties. Many of these capacities are rooted in symbolic language and are therefore unlikely to be shared with nonhuman animals. However, a subset of these skills is shared with other animals, and this set is considered a cognitive vestige of our common evolutionary history. Current evidence indicates that humans and nonhuman animals share a core set of abilities for representing and comparing approximate numerosities nonverbally; however, it remains unclear whether nonhuman animals can perform approximate mental arithmetic. Here we show that monkeys can mentally add the numerical values of two sets of objects and choose a visual array that roughly corresponds to the arithmetic sum of these two sets. Furthermore, monkeys' performance during these calculations adheres to the same pattern as humans tested on the same nonverbal addition task. Our data demonstrate that nonverbal arithmetic is not unique to humans but is instead part of an evolutionarily primitive system for mathematical thinking shared by monkeys.

  14. Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae

    Directory of Open Access Journals (Sweden)

    Reaves Erik J

    2012-05-01

    Full Text Available Abstract Background Rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP. To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus. Methods Eight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R and observed for >130 days. Oral and blood samples were collected and analyzed. Results Two monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D. was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429. No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody. Discussion This study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically

  15. Vicarious learning from human models in monkeys.

    Directory of Open Access Journals (Sweden)

    Rossella Falcone

    Full Text Available We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was apparent from the first trial of the test phase, confirming the ability of monkeys to learn by vicarious observation of human models.

  16. Get the Monkey off Your Back

    Science.gov (United States)

    Ciabattini, David; Custer, Timothy J.

    2008-01-01

    Monkeys are the problems that need solutions, the tasks that need to be accomplished, the decisions that need to be made, and the actions that need to be taken. According to a theory, people carry monkeys around on their backs until they can successfully shift their burden to someone else and the monkey leaps from one back to the next. Managers…

  17. Heterochrony and cross-species intersensory matching by infant vervet monkeys.

    Directory of Open Access Journals (Sweden)

    Shahin Zangenehpour

    Full Text Available Understanding the evolutionary origins of a phenotype requires understanding the relationship between ontogenetic and phylogenetic processes. Human infants have been shown to undergo a process of perceptual narrowing during their first year of life, whereby their intersensory ability to match the faces and voices of another species declines as they get older. We investigated the evolutionary origins of this behavioral phenotype by examining whether or not this developmental process occurs in non-human primates as well.We tested the ability of infant vervet monkeys (Cercopithecus aethiops, ranging in age from 23 to 65 weeks, to match the faces and voices of another non-human primate species (the rhesus monkey, Macaca mulatta. Even though the vervets had no prior exposure to rhesus monkey faces and vocalizations, our findings show that infant vervets can, in fact, recognize the correspondence between rhesus monkey faces and voices (but indicate that they do so by looking at the non-matching face for a greater proportion of overall looking time, and can do so well beyond the age of perceptual narrowing in human infants. Our results further suggest that the pattern of matching by vervet monkeys is influenced by the emotional saliency of the Face+Voice combination. That is, although they looked at the non-matching screen for Face+Voice combinations, they switched to looking at the matching screen when the Voice was replaced with a complex tone of equal duration. Furthermore, an analysis of pupillary responses revealed that their pupils showed greater dilation when looking at the matching natural face/voice combination versus the face/tone combination.Because the infant vervets in the current study exhibited cross-species intersensory matching far later in development than do human infants, our findings suggest either that intersensory perceptual narrowing does not occur in Old World monkeys or that it occurs later in development. We argue that these

  18. Head Rotation Detection in Marmoset Monkeys

    Science.gov (United States)

    Simhadri, Sravanthi

    Head movement is known to have the benefit of improving the accuracy of sound localization for humans and animals. Marmoset is a small bodied New World monkey species and it has become an emerging model for studying the auditory functions. This thesis aims to detect the horizontal and vertical rotation of head movement in marmoset monkeys. Experiments were conducted in a sound-attenuated acoustic chamber. Head movement of marmoset monkey was studied under various auditory and visual stimulation conditions. With increasing complexity, these conditions are (1) idle, (2) sound-alone, (3) sound and visual signals, and (4) alert signal by opening and closing of the chamber door. All of these conditions were tested with either house light on or off. Infra-red camera with a frame rate of 90 Hz was used to capture of the head movement of monkeys. To assist the signal detection, two circular markers were attached to the top of monkey head. The data analysis used an image-based marker detection scheme. Images were processed using the Computation Vision Toolbox in Matlab. The markers and their positions were detected using blob detection techniques. Based on the frame-by-frame information of marker positions, the angular position, velocity and acceleration were extracted in horizontal and vertical planes. Adaptive Otsu Thresholding, Kalman filtering and bound setting for marker properties were used to overcome a number of challenges encountered during this analysis, such as finding image segmentation threshold, continuously tracking markers during large head movement, and false alarm detection. The results show that the blob detection method together with Kalman filtering yielded better performances than other image based techniques like optical flow and SURF features .The median of the maximal head turn in the horizontal plane was in the range of 20 to 70 degrees and the median of the maximal velocity in horizontal plane was in the range of a few hundreds of degrees per

  19. "Zeroing" in on mathematics in the monkey brain.

    Science.gov (United States)

    Beran, Michael J

    2016-03-01

    A new study documented that monkeys showed selective neuronal responding to the concept of zero during a numerical task, and that there were two distinct classes of neurons that coded the absence of stimuli either through a discrete activation pattern (zero or not zero) or a continuous one for which zero was integrated with other numerosities in the relative rate of activity. These data indicate that monkeys, like humans, have a concept of zero that is part of their analog number line but that also may have unique properties compared to other numerosities.

  20. The properties of B-form monoamine oxidase in mitochondria from monkey platelet.

    Science.gov (United States)

    Obata, Toshio; Aomine, Masahiro

    The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.

  1. Sporadic Premature Aging in a Japanese Monkey: A Primate Model for Progeria

    Science.gov (United States)

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

    2014-01-01

    In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes. PMID:25365557

  2. Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

    Directory of Open Access Journals (Sweden)

    James N Mubiru

    Full Text Available The function of prostate-specific antigen (PSA is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes, cynomolgus monkeys (Macaca fascicularis, baboons (Papio hamadryas anubis, and African green monkeys (Chlorocebus aethiops. Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203.

  3. Vicarious Learning from Human Models in Monkeys

    OpenAIRE

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

    We examined whether monkeys can learn by observing a human model, through vicarious learning. Two monkeys observed a human model demonstrating an object-reward association and consuming food found underneath an object. The monkeys observed human models as they solved more than 30 learning problems. For each problem, the human models made a choice between two objects, one of which concealed a piece of apple. In the test phase afterwards, the monkeys made a choice of their own. Learning was app...

  4. Gastrointestinal decontamination in healthy and lethally irradiated monkeys

    International Nuclear Information System (INIS)

    Hendriks, W.D.H.

    1980-01-01

    In periods of extreme immunosuppression, infections which are often life-threatening, frequently occur. In an attempt to prevent such infections in lethally irradiated rhesus monkeys, the animals were subjected to strict reverse isolation prior to irradiation and administrated orally with nonabsorbable antibiotics in order to eliminate their microflora. The antibiotic combination was selected on the basis of a sensitivity test and was added to the liquid food supply. To rapidly achieve a high bactericidal concentration in the intestine, the same antibiotics were additionally given orally for 5 days. The microflora was reduced rapidly; within a few days sterile cultures were obtained. Particularly after discontinuation of the administration of the additional antibiotics were colonizations found. In contrast to colonizations persisting from the first day of treatment on, the first were rather easy to suppress. (Auth.)

  5. Comparative plasma lipidome between human and cynomolgus monkey: are plasma polar lipids good biomarkers for diabetic monkeys?

    Directory of Open Access Journals (Sweden)

    Guanghou Shui

    Full Text Available BACKGROUND: Non-human primates (NHP are now being considered as models for investigating human metabolic diseases including diabetes. Analyses of cholesterol and triglycerides in plasma derived from NHPs can easily be achieved using methods employed in humans. Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the plasma lipidome from 16 cynomolgus monkey, Macaca fascicularis, using liquid chromatography coupled with mass spectrometry (LC/MS. We established novel analytical approaches, which are based on a simple gradient elution, to quantify polar lipids in plasma including (i glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA; (ii sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucocyl-ceramide, GluCer; ganglioside mannoside 3, GM3. Lipidomic analysis had revealed that the plasma of human and cynomolgus monkey were of similar compositions, with PC, SM, PE, LPC and PI constituting the major polar lipid species present. Human plasma contained significantly higher levels of plasmalogen PE species (p<0.005 and plasmalogen PC species (p<0.0005, while cynomolgus monkey had higher levels of polyunsaturated fatty acyls (PUFA in PC, PE, PS and PI. Notably, cynomolgus monkey had significantly lower levels of glycosphingolipids, including GluCer (p<0.0005 and GM(3 (p<0.0005, but higher level of Cer (p<0.0005 in plasma than human. We next investigated the biochemical alterations in blood lipids of 8 naturally occurring diabetic cynomolgus monkeys when compared with 8 healthy controls. CONCLUSIONS: For the first time, we demonstrated that the plasma of human and cynomolgus monkey were of similar compositions, but contained different mol distribution of individual molecular species. Diabetic monkeys

  6. Oral administration of live Shigella vaccine candidates in rhesus monkeys show no evidence of competition for colonization and immunogenicity between different serotypes.

    Science.gov (United States)

    Ranallo, R T; Kaminski, R; Baqar, S; Dutta, M; Lugo-Roman, L A; Boren, T; Barnoy, S; Venkatesan, M M

    2014-03-26

    Live oral monovalent Shigella flexneri 2a vaccine candidates as well as bivalent formulations with Shigella sonnei were evaluated in a rhesus monkey model for colonization and immunogenicity. Freshly harvested suspensions of S. flexneri 2a vaccine candidates WRSf2G12 and WRSf2G15 as well as S. sonnei vaccine candidate WRSs3 were nasogastrically administered to groups of rhesus monkeys, Macaca mulatta, either in a monovalent form or when combined with each other. The animals were monitored daily for physical well-being, stools were subjected to quantitative colony immunoblot assays for bacterial excretion and blood and stools were evaluated for humoral and mucosal immune responses. No clinical symptoms were noted in any group of animals and the vaccine candidates were excreted robustly for 48-72h without significant changes in either the magnitude or duration of excretion when given as a monovalent or as bivalent mixtures. Similarly, immunological interferences were not apparent in the magnitude of humoral and mucosal immune responses observed toward Shigella-specific antigens when monkeys were fed monovalent or bivalent formulations. These results predict that a multivalent live oral vaccine of more than one serotype can have a favorable outcome for protection against shigellosis. Published by Elsevier Ltd.

  7. [Explantation method of isolating a persistent tick-borne encephalitis virus from the organs of infected monkeys].

    Science.gov (United States)

    Levina, L S; Pogodina, V V

    1981-01-01

    The method of explantation was used to examine 63 organs from M. rhesus monkeys 92-783 days after intracerebral and subcutaneous inoculation with the Vasilchenko, Aina/1448 and 41/65 strains of tick-borne encephalitis virus. The optimal time for examination of the explants by tests of the hemagglutinating, cytopathogenic activity of the virus and its pathogenicity for mice was found to be the 15th day of cultivation. A comparative study of the properties of 3 isolates obtained from explants of the spleen, liver and subcortical cerebral ganglia 202 and 307 days after inoculation of monkeys was carried out. The isolates differed from the parental TBE virus strains by their capacity to form small plaques in PEKV cell cultures (pig embryo kidney cells in versen medium).

  8. Electrons at the monkey saddle: A multicritical Lifshitz point

    Science.gov (United States)

    Shtyk, A.; Goldstein, G.; Chamon, C.

    2017-01-01

    We consider two-dimensional interacting electrons at a monkey saddle with dispersion ∝px3-3 pxpy2 . Such a dispersion naturally arises at the multicritical Lifshitz point when three Van Hove saddles merge in an elliptical umbilic elementary catastrophe, which we show can be realized in biased bilayer graphene. A multicritical Lifshitz point of this kind can be identified by its signature Landau level behavior Em∝(Bm ) 3 /2 and related oscillations in thermodynamic and transport properties, such as de Haas-Van Alphen and Shubnikov-de Haas oscillations, whose period triples as the system crosses the singularity. We show, in the case of a single monkey saddle, that the noninteracting electron fixed point is unstable to interactions under the renormalization-group flow, developing either a superconducting instability or non-Fermi-liquid features. Biased bilayer graphene, where there are two non-nested monkey saddles at the K and K' points, exhibits an interplay of competing many-body instabilities, namely, s -wave superconductivity, ferromagnetism, and spin- and charge-density waves.

  9. Socialization of adult owl monkeys (Aotus sp.) in Captivity.

    Science.gov (United States)

    Williams, Lawrence E; Coke, C S; Weed, J L

    2017-01-01

    Social housing has often been recommended as one-way to address the psychological well-being of captive non-human primates. Published reports have examined methods to socialize compatible animals by forming pairs or groups. Successful socialization rates vary depending on the species, gender, and environment. This study presents a retrospective look at pairing attempts in two species of owl monkeys, Aotus nancymaae and A. azarae, which live in monogamous pairs in the wild. The results of 477 pairing attempt conducted with captive, laboratory housed owl monkeys and 61 hr of behavioral observations are reported here. The greatest success pairing these owl monkeys occurred with opposite sex pairs, with an 82% success rate. Opposite sex pairs were more successful when females were older than males. Female-female pairs were more successful than male-male (MM) pairs (62% vs 40%). Successful pairs stayed together between 3 and 7 years before the animals were separated due to social incompatibility. Vigilance, eating, and sleeping during introductions significantly predicted success, as did the performance of the same behavior in both animals. The results of this analysis show that it is possible to give captive owl monkeys a social alternative even if species appropriate social partners (i.e., opposite sex partners) are not available. The focus of this report is a description of one potential way to enhance the welfare of a specific new world primate, the owl monkey, under laboratory conditions. More important is how the species typical social structure of owl monkeys in nature affects the captive management of this genus. Am. J. Primatol. 79:e22521, 2017. © 2015 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Widespread and evolutionary analysis of a MITE family Monkey King in Brassicaceae.

    Science.gov (United States)

    Dai, Shutao; Hou, Jinna; Long, Yan; Wang, Jing; Li, Cong; Xiao, Qinqin; Jiang, Xiaoxue; Zou, Xiaoxiao; Zou, Jun; Meng, Jinling

    2015-06-19

    Miniature inverted repeat transposable elements (MITEs) are important components of eukaryotic genomes, with hundreds of families and many copies, which may play important roles in gene regulation and genome evolution. However, few studies have investigated the molecular mechanisms involved. In our previous study, a Tourist-like MITE, Monkey King, was identified from the promoter region of a flowering time gene, BnFLC.A10, in Brassica napus. Based on this MITE, the characteristics and potential roles on gene regulation of the MITE family were analyzed in Brassicaceae. The characteristics of the Tourist-like MITE family Monkey King in Brassicaceae, including its distribution, copies and insertion sites in the genomes of major Brassicaceae species were analyzed in this study. Monkey King was actively amplified in Brassica after divergence from Arabidopsis, which was indicated by the prompt increase in copy number and by phylogenetic analysis. The genomic variations caused by Monkey King insertions, both intra- and inter-species in Brassica, were traced by PCR amplification. Genomic sequence analysis showed that most complete Monkey King elements are located in gene-rich regions, less than 3kb from genes, in both the B. rapa and A. thaliana genomes. Sixty-seven Brassica expressed sequence tags carrying Monkey King fragments were also identified from the NCBI database. Bisulfite sequencing identified specific DNA methylation of cytosine residues in the Monkey King sequence. A fragment containing putative TATA-box motifs in the MITE sequence could bind with nuclear protein(s) extracted from leaves of B. napus plants. A Monkey King-related microRNA, bna-miR6031, was identified in the microRNA database. In transgenic A. thaliana, when the Monkey King element was inserted upstream of 35S promoter, the promoter activity was weakened. Monkey King, a Brassicaceae Tourist-like MITE family, has amplified relatively recently and has induced intra- and inter-species genomic

  11. Chemotherapy of second stage human African trypanosomiasis: comparison between the parenteral diamidine DB829 and its oral prodrug DB868 in vervet monkeys.

    Directory of Open Access Journals (Sweden)

    John K Thuita

    2015-02-01

    Full Text Available Human African trypanosomiasis (HAT, sleeping sickness ranks among the most neglected tropical diseases based on limited availability of drugs that are safe and efficacious, particularly against the second stage (central nervous system [CNS] of infection. In response to this largely unmet need for new treatments, the Consortium for Parasitic Drug Development developed novel parenteral diamidines and corresponding oral prodrugs that have shown cure of a murine model of second stage HAT. As a rationale for selection of one of these compounds for further development, the pharmacokinetics and efficacy of intramuscular (IM active diamidine 2,5-bis(5-amidino-2-pyridylfuran (DB829; CPD-0802 and oral prodrug2,5-bis[5-(N-methoxyamidino-2-pyridyl]furan (DB868 were compared in the vervet monkey model of second stage HAT. Treatment was initiated 28 days post-infection of monkeys with T. b. rhodesiense KETRI 2537. Results showed that IM DB829 at 5 mg/kg/day for 5 consecutive days, 5 mg/kg/day every other day for 5 doses, or 2.5 mg/kg/day for 5 consecutive days cured all monkeys (5/5. Oral DB868 was less successful, with no cures (0/2 at 3 mg/kg/day for 10 days and cure rates of 1/4 at 10 mg/kg/day for 10 days and 20 mg/kg/day for 10 days; in total, only 2/10 monkeys were cured with DB868 dose regimens. The geometric mean plasma Cmax of IM DB829 at 5 mg/kg following the last of 5 doses was 25-fold greater than that after 10 daily oral doses of DB868 at 20 mg/kg. These data suggest that the active diamidine DB829, administered IM, should be considered for further development as a potential new treatment for second stage HAT.

  12. Serological reactions in Rhesus monkeys inoculated with the 17D strain of yellow fever virus.

    Science.gov (United States)

    GROOT, H

    1962-01-01

    Haemagglutination-inhibition tests, which depend on the appearance of haemagglutination-inhibiting antibodies in the serum in virus infections, are in common use in the study of arthropod-borne diseases. This paper contains the results of an investigation into the appearance and pattern of haemagglutination-inhibiting antibodies in the serum of rhesus monkeys inoculated intracerebrally with the 17D strain of yellow fever virus during the testing of seed lots of yellow fever vaccine. These antibodies appeared on the tenth day after inoculation, and were still demonstrable four years later. In all of the eight monkeys tested complement-fixing and neutralizing antibodies against yellow fever antigens also developed, and in six out of the eight heterologous antigens developed.

  13. Intracerebral infection of Cebus apella with the XJ-Clone 3 strain of Junín virus.

    Science.gov (United States)

    Carballal, G; Oubiña, J R; Molinas, F C; Nagle, C; de la Vega, M T; Videla, C; Elsner, B

    1987-03-01

    To assess the usefulness of the South American primate Cebus apella as a model for neurovirulence of Junín virus, eight monkeys were inoculated with 10(5) LD50 of the attenuated XJ-Clone 3 Junín virus strain by the intrathalamic route. After the second week, weight loss and polyadenopathies were observed in most animals, one-half of which had a transient leukothrombocytopenia. Moderate clinical central nervous system (CNS) involvement was present in four of eight monkeys, while the rest had only mild neurologic signs. All recovered except one, which developed a deep coma and was killed in a pre-mortem stage at 18 days post-infection (pi). Junín virus was isolated from the throat from five, from the blood from three, and from the brain from two monkeys. In the most severely ill animal, virus titers higher than viremia were detected in both inoculated and contralateral brain hemispheres, as well as in lung, lymph node, and small intestine. Junín antigens and "in vivo" bound immunoglobulins were detected by immunofluorescence (IF) in the brain of four animals at 18, 21, 40, and 155 days pi. Moderate lymphocytic parenchymal and meningeal infiltration were observed in the brain of four animals, and gliosis was also present in the most affected monkey. Although the clinical response to infection was not uniform, all infected monkeys developed high IF antibodies. Cebus apella cannot be used as a highly sensitive model for Argentine hemorrhagic fever (AHF). However, the results obtained show that the XJ-Clone 3 strain can replicate in the primate CNS and to induce lesions and immunoglobulin deposition. In addition, viral persistence is suggested by the late detection of viral antigens in brain at 40 and 155 days pi.

  14. Ethograms indicate stable well-being during prolonged training phases in rhesus monkeys used in neurophysiological research.

    Science.gov (United States)

    Hage, Steffen R; Ott, Torben; Eiselt, Anne-Kathrin; Jacob, Simon N; Nieder, Andreas

    2014-01-01

    Awake, behaving rhesus monkeys are widely used in neurophysiological research. Neural signals are typically measured from monkeys trained with operant conditioning techniques to perform a variety of behavioral tasks in exchange for rewards. Over the past years, monkeys' psychological well-being during experimentation has become an increasingly important concern. We suggest objective criteria to explore whether training sessions during which the monkeys work under controlled water intake over many days might affect their behavior. With that aim, we analyzed a broad range of species-specific behaviors over several months ('ethogram') and used these ethograms as a proxy for the monkeys' well-being. Our results show that monkeys' behavior during training sessions is unaffected by the duration of training-free days in-between. Independently of the number of training-free days (two or nine days) with ad libitum food and water supply, the monkeys were equally active and alert in their home group cages during training phases. This indicates that the monkeys were well habituated to prolonged working schedules and that their well-being was stably ensured during the training sessions.

  15. Epidurography with metrizamide in Rhesus monkeys

    International Nuclear Information System (INIS)

    Kido, D.K.; Baker, R.A.; Saubermann, A.; Salem, J.; Schoene, W.C.; Fournier, P.

    1980-01-01

    Epidurography with metrizamide was performed on 9 Rhesus monkeys; physiologic saline was substituted for metrizamide in 3 control monkeys. Metrizamide successfully outlined the epidural space without causing any adverse clinical effects or direct tissue injury. (Auth.)

  16. Placental Transport of Zidovudine in the Rhesus Monkey

    OpenAIRE

    Ridgway III, Louis E.; King, Thomas S.; Henderson, George I.; Schenker, Steven; Schenken, Robert S.

    1993-01-01

    Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Ma...

  17. Identification of a Surrogate Marker for Infection in the African Green Monkey Model of Inhalation Anthrax

    National Research Council Canada - National Science Library

    Rossi, Cynthia A; Ulrich, Melanie; Norris, Sarah; Reed, Douglas S; Pitt, Louise M; Leffel, Elizabeth K

    2008-01-01

    .... In this study, we exposed African green monkeys to B. anthracis spores and examined clinical signs and physiological parameters to include fever, heart rate, complete blood counts and bacteremia, as well as the PCR and electrochemiluminescence (ECL...

  18. Characterization of Mason--Pfizer monkey virus-induced cell fusion

    International Nuclear Information System (INIS)

    Chatterjee, S.; Hunter, E.

    1979-01-01

    The characteristics and requirements of multinucleate cell (syncytium) induction by Mason--Pfizer monkey virus (M-PMV) on human and non-human primate cells have been investigated. Multinucleate cell induction by this D-type retrovirus shows single-hit kinetics on human foreskin and rhesus monkey fetal lung cells. The peak of syncytium-forming activity in an isopycnic sucrose gradient coincides with the peak of M-PMV virions as assessed by electron microscopy and analysis of viral polypeptides. Unlike the paramyxoviruses, M-PMV does not induce early cell fusion when added in high concentrations to the target cells. Furthermore, multinucleate cell formation is maximal 48 hr postinfection and the size of the syncytia remains constant after this time. Ultraviolet irradiation of M-PMV reduces its ability to form syncytia and to replicate with single-hit kinetics, suggesting that a functional viral genome is required for syncytium formation. Proviral DNA synthesis and assembly of virions are not necessary for cell fusion since the addition of cytosine arabinoside at concentrations which block virus replication has little effect on multinucleate cell formation. Moreover both multinucleate cells lacking detectable intracellular virus polypeptides, and groups of individual, nonfused but brightly staining cells can be observed in immunofluorescence assays at times when multinucleate cell formation is maximal. Cell fusion is inhibited by the addition of cycloheximide during the first 12 hr of infection, suggesting that de novo protein synthesis is required for multinucleate cell formation. The possibility that the translation of genomic RNA yields a fusion-inducing product is discussed

  19. Dynamic interaction between STLV-1 proviral load and T-cell response during chronic infection and after immunosuppression in non-human primates.

    Directory of Open Access Journals (Sweden)

    Sandrine Souquière

    Full Text Available We used mandrills (Mandrillus sphinx naturally infected with simian T-cell leukemia virus type 1 (STLV-1 as a model for evaluating the influence of natural STLV-1 infection on the dynamics and evolution of the immune system during chronic infection. Furthermore, in order to evaluate the role of the immune system in controlling the infection during latency, we induced immunosuppression in the infected monkeys. We first showed that the STLV-1 proviral load was higher in males than in females and increased significantly with the duration of infection: mandrills infected for 10-6 years had a significantly higher proviral load than those infected for 2-4 years. Curiously, this observation was associated with a clear reduction in CD4+ T-cell number with age. We also found that the percentage of CD4(+ T cells co-expressing the activation marker HLA-DR and the mean percentage of CD25(+ in CD4(+ and CD8(+ T cells were significantly higher in infected than in uninfected animals. Furthermore, the STLV-1 proviral load correlated positively with T-cell activation but not with the frequency of T cells secreting interferon gamma in response to Tax peptides. Lastly, we showed that, during immunosuppression in infected monkeys, the percentages of CD8(+ T cells expressing HLA-DR(+ and of CD4(+ T cells expressing the proliferation marker Ki67 decreased significantly, although the percentage of CD8(+ T cells expressing HLA-DR(+ and Ki67 increased significantly by the end of treatment. Interestingly, the proviral load increased significantly after immunosuppression in the monkey with the highest load. Our study demonstrates that mandrills naturally infected with STLV-1 could be a suitable model for studying the relations between host and virus. Further studies are needed to determine whether the different compartments of the immune response during infection induce the long latency by controlling viral replication over time. Such studies would provide important

  20. Autoshaping in Japanese Monkeys (Macaca Fuscata)

    OpenAIRE

    Itakura, Shoji; Fushimi, Takao; Asano, Toshio; Shoji, Itakura; Takao, Fushimi; Toshio, Asano

    1992-01-01

    Three Japanese monkeys were exposed to autoshaping and omission procedures. The Japanese momkeys seemed to be more sensitive to response-reinforcer contingency than to stimulus-reinforcer contingency. These results were compared with pigeons and squirrel monkeys in the previous reports.

  1. Somatosensory deficits in monkeys treated with misonidazole

    International Nuclear Information System (INIS)

    Maurissen, J.P.J.; Conroy, P.J.; Passalacqua, W.; Von Burg, R.; Weiss, B.; Sutherland, R.M.

    1981-01-01

    Misonidazole, a hypoxic cell radiosensitizer, can produce peripheral sensory disorders in humans. It has been studied in monkeys with a computer-controlled system for evaluating vibration sensitivity. Monkeys were trained to report when vibration was stimulating the finger tip. Sinusoidal vibrations of several frequencies were presented. Two monkeys were dosed with misonidazole and their vibration sensitivity tested. They received a dose of 3 g/m 2 (about 180 mg/kg) twice weekly over a period of 6 to 10 weeks. An amplitude-frequency detection function was determined for each monkey before and after drug treatment. An analysis of covariance comparing polynomial regressions was performed. A significant difference (p < 0.001) was found between control and experimental curves in both monkeys. Pharmacokinetic data indicated a half-life of the drug in blood of about 4 to 5 hr. The overall half-life for elimination did not increase throughout prolonged treatment with msonidazole. Neither motor nor sensory nerve conduction velocity was reduced after treatment

  2. Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection.

    Directory of Open Access Journals (Sweden)

    Girish Ramachandran

    2017-08-01

    Full Text Available Salmonella Typhimurium sequence type (ST 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50 was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

  3. Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection.

    Science.gov (United States)

    Ramachandran, Girish; Panda, Aruna; Higginson, Ellen E; Ateh, Eugene; Lipsky, Michael M; Sen, Sunil; Matson, Courtney A; Permala-Booth, Jasnehta; DeTolla, Louis J; Tennant, Sharon M

    2017-08-01

    Salmonella Typhimurium sequence type (ST) 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50) was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

  4. Hemorrhoids: an experimental model in monkeys

    Directory of Open Access Journals (Sweden)

    Plapler Hélio

    2006-01-01

    Full Text Available PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We describe a simple, easy and reliable experimental model to produce hemorrhoids in monkeys. METHODS: 14 monkeys (Cebus apella were used. After general anesthesia, hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is very alike to humans. The vein was located through a perianal incision, dissected and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread. Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days later there were hemorrhoidal piles in the anus in fifty percent (50% of the animals. Outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering. CONCLUSION: This is an affordable and reliable experimental model to induce hemorrhoids for experimental studies.

  5. Processing of vocalizations in humans and monkeys: A comparative fMRI study

    International Nuclear Information System (INIS)

    Joly, Olivier; Orban, Guy A.; Pallier, Christophe; Ramus, Franck; Pressnitzer, Daniel; Vanduffel, Wim

    2012-01-01

    Humans and many other animals use acoustical signals to mediate social interactions with con-specifics. The evolution of sound-based communication is still poorly understood and its neural correlates have only recently begun to be investigated. In the present study, we applied functional MRI to humans and macaque monkeys listening to identical stimuli in order to compare the cortical networks involved in the processing of vocalizations. At the first stages of auditory processing, both species showed similar fMRI activity maps within and around the lateral sulcus (the Sylvian fissure in humans). Monkeys showed remarkably similar responses to monkey calls and to human vocal sounds (speech or otherwise), mainly in the lateral sulcus and the adjacent superior temporal gyrus (STG). In contrast, a preference for human vocalizations and especially for speech was observed in the human STG and superior temporal sulcus (STS). The STS and Broca's region were especially responsive to intelligible utterances. The evolution of the language faculty in humans appears to have recruited most of the STS. It may be that in monkeys, a much simpler repertoire of vocalizations requires less involvement of this temporal territory. (authors)

  6. Predictive and tempo-flexible synchronization to a visual metronome in monkeys.

    Science.gov (United States)

    Takeya, Ryuji; Kameda, Masashi; Patel, Aniruddh D; Tanaka, Masaki

    2017-07-21

    Predictive and tempo-flexible synchronization to an auditory beat is a fundamental component of human music. To date, only certain vocal learning species show this behaviour spontaneously. Prior research training macaques (vocal non-learners) to tap to an auditory or visual metronome found their movements to be largely reactive, not predictive. Does this reflect the lack of capacity for predictive synchronization in monkeys, or lack of motivation to exhibit this behaviour? To discriminate these possibilities, we trained monkeys to make synchronized eye movements to a visual metronome. We found that monkeys could generate predictive saccades synchronized to periodic visual stimuli when an immediate reward was given for every predictive movement. This behaviour generalized to novel tempi, and the monkeys could maintain the tempo internally. Furthermore, monkeys could flexibly switch from predictive to reactive saccades when a reward was given for each reactive response. In contrast, when humans were asked to make a sequence of reactive saccades to a visual metronome, they often unintentionally generated predictive movements. These results suggest that even vocal non-learners may have the capacity for predictive and tempo-flexible synchronization to a beat, but that only certain vocal learning species are intrinsically motivated to do it.

  7. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    Science.gov (United States)

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. Copyright © 2015 the authors 0270-6474/15/358345-14$15.00/0.

  8. Gastrointestinal Parasites of Ecuadorian Mantled Howler Monkeys (Alouatta palliata aequatorialis) Based on Fecal Analysis.

    Science.gov (United States)

    Helenbrook, William D; Wade, Susan E; Shields, William M; Stehman, Stephen V; Whipps, Christopher M

    2015-06-01

    An analysis of gastrointestinal parasites of Ecuadorian mantled howler monkeys, Alouatta palliata aequatorialis, was conducted based on examination of fecal smears, flotations, and sedimentations. At least 1 type of parasite was detected in 97% of the 96 fecal samples screened across 19 howler monkey groups using these techniques. Samples averaged 3.6 parasite species per individual (±1.4 SD). Parasites included species representing genera of 2 apicomplexans: Cyclospora sp. (18% of individual samples) and Isospora sp. (3%); 6 other protozoa: Balantidium sp. (9%), Blastocystis sp. (60%), Chilomastix sp. (4%), Dientamoeba sp. (3%), Entamoeba species (56%), Iodamoeba sp. (5%); 4 nematodes: Enterobius sp. (3%), Capillaria sp. (78%), Strongyloides spp. (88%) which included 2 morphotypes, Trypanoxyuris sp. (12%); and the platyhelminth Controrchis sp. (15%). A statistically significant positive correlation was found between group size and each of 3 different estimators of parasite species richness adjusted for sampling effort (ICE: r(2) = 0.24, P = 0.05; Chao2: r(2) = 0.25, P = 0.05, and Jackknife: r(2) = 0.31, P = 0.03). Two significant associations between co-infecting parasites were identified. Based on the prevalence data, individuals infected with Balantidium sp. were more likely to also be infected with Isospora sp. (χ(2) = 6.02, P = 0.01), while individuals harboring Chilomastix sp. were less likely to have Capillaria sp. present (χ(2) = 4.03, P = 0.04).

  9. Sexual Transmission of XMRV: A Potential Infection Route

    Directory of Open Access Journals (Sweden)

    Prachi Sharma

    2011-01-01

    Full Text Available Although XMRV dissemination in humans is a matter of debate, the prostate of select patients seem to harbor XMRV, which raises questions about its potential route of transmission. We established a model of infection in rhesus macaques inoculated with XMRV. In spite of the intravenous inoculation, all infected macaques exhibited readily detectable XMRV signal in the reproductive tract of all 4 males and 1 female during both acute and chronic infection stages. XMRV showed explosive growth in the acini of prostate during acute but not chronic infection. In seminal vesicles, epididymis, and testes, XMRV protein production was detected throughout infection in interstitial or epithelial cells. In the female monkey, epithelial cells in the cervix and vagina were also positive for XMRV gag. The ready detection of XMRV in the reproductive tract of male and female macaques infected intravenously suggests the potential for sexual transmission for XMRV.

  10. Autonomous replication of plasmids bearing monkey DNA origin-enriched sequences

    International Nuclear Information System (INIS)

    Frappier, L.; Zannis-Hadjopoulos, M.

    1987-01-01

    Twelve clones of origin-enriched sequences (ORS) isolated from early replicating monkey (CV-1) DNA were examined for transient episomal replication in transfected CV-1, COS-7, and HeLa cells. Plasmid DNA was isolated at time intervals after transfection and screened by the Dpn I resistance assay or by the bromodeoxyuridine substitution assay to differentiate between input and replicated DNA. The authors have identified four monkey ORS (ORS3, -8, -9, and -12) that can support plasmid replication in mammalian cells. This replication is carried out in a controlled and semiconservative manner characteristic of mammalian replicons. ORS replication was most efficient in HeLa cells. Electron microscopy showed ORS8 and ORS12 plasmids of the correct size with replication bubbles. Using a unique restriction site in ORS12, we have mapped the replication bubble within the monkey DNA sequence

  11. The neonatal marmoset monkey ovary is very primitive exhibiting many oogonia

    Science.gov (United States)

    Fereydouni, B; Drummer, C; Aeckerle, N; Schlatt, S; Behr, R

    2014-01-01

    Oogonia are characterized by diploidy and mitotic proliferation. Human and mouse oogonia express several factors such as OCT4, which are characteristic of pluripotent cells. In human, almost all oogonia enter meiosis between weeks 9 and 22 of prenatal development or undergo mitotic arrest and subsequent elimination from the ovary. As a consequence, neonatal human ovaries generally lack oogonia. The same was found in neonatal ovaries of the rhesus monkey, a representative of the old world monkeys (Catarrhini). By contrast, proliferating oogonia were found in adult prosimians (now called Strepsirrhini), which is a group of ‘lower’ primates. The common marmoset monkey (Callithrix jacchus) belongs to the new world monkeys (Platyrrhini) and is increasingly used in reproductive biology and stem cell research. However, ovarian development in the marmoset monkey has not been widely investigated. Herein, we show that the neonatal marmoset ovary has an extremely immature histological appearance compared with the human ovary. It contains numerous oogonia expressing the pluripotency factors OCT4A, SALL4, and LIN28A (LIN28). The pluripotency factor-positive germ cells also express the proliferation marker MKI67 (Ki-67), which has previously been shown in the human ovary to be restricted to premeiotic germ cells. Together, the data demonstrate the primitiveness of the neonatal marmoset ovary compared with human. This study may introduce the marmoset monkey as a non-human primate model to experimentally study the aspects of primate primitive gonad development, follicle assembly, and germ cell biology in vivo. PMID:24840529

  12. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa

    2014-01-01

    , therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model...... on Tarlov's scale and our established behavioral tests for monkeys. CONCLUSION: Our findings have indicated that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque monkeys. Additional studies are necessary to determine the im- provement mechanisms after cell transplantation....

  13. Radioimmunoassay of parathyroid hormone (parathyrin) in monkey and man

    International Nuclear Information System (INIS)

    Hargis, G.K.; Williams, G.A.; Reynolds, W.A.; Kawahara, W.; Jackson, B.; Bowser, E.N.; Pitkin, R.M.

    1977-01-01

    A radioimmunoassay for rhesus monkey and human innumoreactive parathyrin was developed in which a selected anti-bovine parathyrin antiserum, radioiodinated purified bovine parathyrin tracer, and human parathyroid tissue-culture media standards were used. The resulting data indicate that the method is sensitive, specific, accurate and reproducible; it is valid for both the rhesus monkey and the human; the serum immunoreactive parathyrin concentration of the monkey is essentially the same as that in man; monkey immunoreactive parathyrin responds to changes in serum calcium concentration similarly to that in man; and the rhesus monkey is therefore a suitable species in which to study parathyroid physiology, from which conclusions can be applied to the human

  14. What do monkeys' music choices mean?

    Science.gov (United States)

    Lamont, Alexandra M

    2005-08-01

    McDermott and Hauser have recently shown that although monkeys show some types of preferences for sound, preferences for music are found only in humans. This suggests that music might be a relatively recent adaptation in human evolution. Here, I focus on the research methods used by McDermott and Hauser, and consider the findings in relation to infancy research and music psychology.

  15. Limited Susceptibility of Cynomolgus Monkeys (Macaca fascicularis) to Leprosy after Experimental Administration of Mycobacterium leprae

    Science.gov (United States)

    Walsh, Gerald P.; Dela Cruz, Eduardo C.; Abalos, Rodolfo M.; Tan, Esterlina V.; Fajardo, Tranquilino T.; Villahermosa, Laarni G.; Cellona, Roland V.; Balagon, Maria V.; White, Valerie A.; Saunderson, Paul R.; Walsh, Douglas S.

    2012-01-01

    Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis—importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1–19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration. PMID:22855766

  16. Event-based proactive interference in rhesus monkeys.

    Science.gov (United States)

    Devkar, Deepna T; Wright, Anthony A

    2016-10-01

    Three rhesus monkeys (Macaca mulatta) were tested in a same/different memory task for proactive interference (PI) from prior trials. PI occurs when a previous sample stimulus appears as a test stimulus on a later trial, does not match the current sample stimulus, and the wrong response "same" is made. Trial-unique pictures (scenes, objects, animals, etc.) were used on most trials, except on trials where the test stimulus matched potentially interfering sample stimulus from a prior trial (1, 2, 4, 8, or 16 trials prior). Greater interference occurred when fewer trials separated interference and test. PI functions showed a continuum of interference. Delays between sample and test stimuli and intertrial intervals were manipulated to test how PI might vary as a function of elapsed time. Contrary to a similar study with pigeons, these time manipulations had no discernable effect on the monkey's PI, as shown by compete overlap of PI functions with no statistical differences or interactions. These results suggested that interference was strictly based upon the number of intervening events (trials with other pictures) without regard to elapsed time. The monkeys' apparent event-based interference was further supported by retesting with a novel set of 1,024 pictures. PI from novel pictures 1 or 2 trials prior was greater than from familiar pictures, a familiar set of 1,024 pictures. Moreover, when potentially interfering novel stimuli were 16 trials prior, performance accuracy was actually greater than accuracy on baseline trials (no interference), suggesting that remembering stimuli from 16 trials prior was a cue that this stimulus was not the sample stimulus on the current trial-a somewhat surprising conclusion particularly given monkeys.

  17. Stable isotope ratios indicate diet and habitat use in New World monkeys.

    Science.gov (United States)

    Schoeninger, M J; Iwaniec, U T; Glander, K E

    1997-05-01

    This paper demonstrates the use of stable isotope ratios of carbon and nitrogen in animal tissue for indicating aspects of species behavioral strategy. We analyzed hair from individuals representing four species of New World monkeys (Alouatta palliata, the mantled howler; Ateles geoffroyi, the spider monkey; Cebus capucinus, the capuchin; and Brachyteles arachnoides, the woolly-spider monkey or muriqui) for delta 13C and delta 15N using previously developed methods. There are no significant differences in either carbon or nitrogen ratios between sexes, sampling year, or year of analysis. Seasonal differences in delta 13C reached a low level of significance but do not affect general patterns. Variation within species was similar to that recorded previously within single individuals. The omega 13C data show a bimodal distribution with significant difference between the means. The two monkey populations living in an evergreen forest were similar to each other and different from the other two monkey populations that inhabited dry, deciduous forests. This bimodal distribution is independent of any particular species' diet and reflects the level of leaf cover in the two types of forest. The delta 15N data display three significantly different modes. The omnivorous capuchins were most positive reflecting a trophic level offset. The spider monkeys and the muriquis were similar to one another and significantly more positive than the howlers. This distribution among totally herbivorous species correlates with the ingestion of legumes by the howler monkey population. In combination, these data indicate that museum-curated primate material can be analyzed to yield information on forest cover and diet in populations and species lacking behavioral data.

  18. Functional Imaging of Audio–Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

    Science.gov (United States)

    Muers, Ross S.; Salo, Emma; Slater, Heather; Petkov, Christopher I.

    2017-01-01

    Abstract The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio–visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio–visual selective attention modulates the primate brain, identify sources for “lost” attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. PMID:28419201

  19. Moonstruck primates: owl monkeys (Aotus need moonlight for nocturnal activity in their natural environment.

    Directory of Open Access Journals (Sweden)

    Eduardo Fernández-Duque

    2010-09-01

    Full Text Available Primates show activity patterns ranging from nocturnality to diurnality, with a few species showing activity both during day and night. Among anthropoids (monkeys, apes and humans, nocturnality is only present in the Central and South American owl monkey genus Aotus. Unlike other tropical Aotus species, the Azara's owl monkeys (A. azarai of the subtropics have switched their activity pattern from strict nocturnality to one that also includes regular diurnal activity. Harsher climate, food availability, and the lack of predators or diurnal competitors, have all been proposed as factors favoring evolutionary switches in primate activity patterns. However, the observational nature of most field studies has limited an understanding of the mechanisms responsible for this switch in activity patterns. The goal of our study was to evaluate the hypothesis that masking, namely the stimulatory and/or inhibitory/disinhibitory effects of environmental factors on synchronized circadian locomotor activity, is a key determinant of the unusual activity pattern of Azara's owl monkeys. We use continuous long-term (6-18 months 5-min-binned activity records obtained with actimeter collars fitted to wild owl monkeys (n =  10 individuals to show that this different pattern results from strong masking of activity by the inhibiting and enhancing effects of ambient luminance and temperature. Conclusive evidence for the direct masking effect of light is provided by data showing that locomotor activity was almost completely inhibited when moonlight was shadowed during three lunar eclipses. Temperature also negatively masked locomotor activity, and this masking was manifested even under optimal light conditions. Our results highlight the importance of the masking of circadian rhythmicity as a determinant of nocturnality in wild owl monkeys and suggest that the stimulatory effects of dim light in nocturnal primates may have been selected as an adaptive response to

  20. Modified Monkey Optimization Algorithm for Solving Optimal Reactive Power Dispatch Problem

    Directory of Open Access Journals (Sweden)

    Kanagasabai Lenin

    2015-04-01

    Full Text Available In this paper, a novel approach Modified Monkey optimization (MMO algorithm for solving optimal reactive power dispatch problem has been presented. MMO is a population based stochastic meta-heuristic algorithm and it is inspired by intelligent foraging behaviour of monkeys. This paper improves both local leader and global leader phases.  The proposed (MMO algorithm has been tested in standard IEEE 30 bus test system and simulation results show the worthy performance of the proposed algorithm in reducing the real power loss.

  1. Evaluation of polymorphonuclear leukocyte chemotaxis of adult and neonatal rhesus monkeys using 51-chromium labeling method

    International Nuclear Information System (INIS)

    Kinoshita, Yo; Masuda, Kiyokazu; Kobayashi, Yohnosuke

    1987-01-01

    Chemotaxis of polymorphonuclear leukocytes (PMN) from heparinized venous blood of 8 adult rhesus monkeys (Macaca Mulatta) and 13 rhesus monkey neonates within 48 hours of birth were evaluated by using 51-chromium labeling method. PMNs were prepared by Ficoll-Hypaque gradient and dextran sedimentation procedures and the final 51-chromium uptake was 3.21 ± 1.27 % to original count. PMN chemotaxis was succeeded by using two different chemotaxis filters (Nuclepore filter on top of Millipore filter) with incubation at 37 deg C for 90 min. The mean value of target: non target ratio (CPM in lower filter with chemoattractant/CPM in lower filter without chemoattractant) of 3.56 ± 2.49 from neonates showed no significant difference from that of 4.44 ± 1.24 from adults. Only about 30 % of neonates showed an impaired chemotaxis, but others showed similar chemotactic activity as adults. The results show that the 51-chromium labeling method is useful to assess neutrophil functions in rhesus monkey species and suggest that host defense mechanism of the rhesus monkey may differ from that of human in neonatal period. (author)

  2. Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

    Science.gov (United States)

    Rinne, Teemu; Muers, Ross S; Salo, Emma; Slater, Heather; Petkov, Christopher I

    2017-06-01

    The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio-visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio-visual selective attention modulates the primate brain, identify sources for "lost" attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. © The Author 2017. Published by Oxford University Press.

  3. De novo DNA methylation during monkey pre-implantation embryogenesis.

    Science.gov (United States)

    Gao, Fei; Niu, Yuyu; Sun, Yi Eve; Lu, Hanlin; Chen, Yongchang; Li, Siguang; Kang, Yu; Luo, Yuping; Si, Chenyang; Yu, Juehua; Li, Chang; Sun, Nianqin; Si, Wei; Wang, Hong; Ji, Weizhi; Tan, Tao

    2017-04-01

    Critical epigenetic regulation of primate embryogenesis entails DNA methylome changes. Here we report genome-wide composition, patterning, and stage-specific dynamics of DNA methylation in pre-implantation rhesus monkey embryos as well as male and female gametes studied using an optimized tagmentation-based whole-genome bisulfite sequencing method. We show that upon fertilization, both paternal and maternal genomes undergo active DNA demethylation, and genome-wide de novo DNA methylation is also initiated in the same period. By the 8-cell stage, remethylation becomes more pronounced than demethylation, resulting in an increase in global DNA methylation. Promoters of genes associated with oxidative phosphorylation are preferentially remethylated at the 8-cell stage, suggesting that this mode of energy metabolism may not be favored. Unlike in rodents, X chromosome inactivation is not observed during monkey pre-implantation development. Our study provides the first comprehensive illustration of the 'wax and wane' phases of DNA methylation dynamics. Most importantly, our DNA methyltransferase loss-of-function analysis indicates that DNA methylation influences early monkey embryogenesis.

  4. Radiation-induced emesis in monkeys

    International Nuclear Information System (INIS)

    Mattsson, J.L.; Yochmowitz, M.G.

    1980-01-01

    To determine the emesis ED 50 for 60 Co radiation, 15 male rhesus monkeys were exposed to whole-body radiation doses ranging from 350 to 550 rad midline tissue dose. An up-and-down sequence of exposures was used. Step size between doses was 50 rad, and dose rate was 20 rad/min. There had been no access to food for 1 to 2 h. The ED 50 +- SE was found to be 446 +- 27 rad. To determine the effect of motion on emesis ED 50 , six more monkeys were exposed to 60 Co radiation as above, except that the chair in which they were seated was oscillated forward and backward 5 to 15 0 (pitch axis) at a variable rate not exceeding 0.3 Hz. Radioemesis ED 50 +- SE with motion was 258 +- 19 rad, a value significantly lower (P < 0.01) than for stationary monkeys

  5. Effects of ionizing radiation on male germ cells of crab-eating monkey

    International Nuclear Information System (INIS)

    Okamoto, Masanori; Kitazuma, Masayuki; Tobari, Izuo

    1989-01-01

    Effects of ionizing radiation on sperm concentration, testicular volume, and sperm shape of the crab-eating monkey were studied by using acute and low dose-rate gamma-ray and X-ray. The animals were acutely irradiated with 0.25-3.00 Gy with Cs-137 gamma-ray at a dose-rate of 0.25 Gy/min. Sperm concentrations were decreased with time after irradiation in a dose-dependent fashion. The time required for the lowest concentration of sperm depended on radiation doses. A linear dose-response relationship was seen for sperm concentrations. In comparing the present results in monkeys to previous results in mice and golden hamsters, the sensitivity of spermatogenic cells in killing effect of gamma ray varied in the following order: monkeys>hamsters>mice. The present monkeys were also subjected to whole-body irradiation with 0.3-1.5 Gy of Cs-137 gamma-ray at 1.8 x 10 -5 Gy/min, for the purpose of estimating low-dose rate irradiation on sperm concentrations, testicular volume and sperm shape. Noticeable changes in either sperm concentration or testicular volume did not occur by irradiation of 0.3 Gy. Sperm concentrations were markedly changed with 1.0 Gy. Changes in sperm concentrations and testicular volume after X-ray irradiation at the dose-rate of 0.32 Gy/min showed that killing effects of X-ray are apparently higher than those of gamma-ray. When the incidence of abnormal head shapes of sperm was examined in monkeys with chronic gamma-ray irradiation, the highest incidence of abnormality was 1.5-1.8% at 0.25-0.50 Gy. The incidence of sperm abnormality in monkeys was comparable to that in hamsters; however, it was markedly higher in mice than monkeys. (Namekawa, K)

  6. Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.

    Science.gov (United States)

    Pan-Zhou, Xin-Ru; Mayes, Benjamin A; Rashidzadeh, Hassan; Gasparac, Rahela; Smith, Steven; Bhadresa, Sanjeev; Gupta, Kusum; Cohen, Marita Larsson; Bu, Charlie; Good, Steven S; Moussa, Adel; Rush, Roger

    2016-10-01

    IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction. Systemic exposures to the main metabolite, 2'-methylguanosine (2'-MeG), were used as a surrogate for liver levels of the pharmacologically active entity 2'-MeG triphosphate, and accordingly, systemic levels of 2'-MeG in the monkey were used to optimize formulations for further clinical development of IDX184. Capsule formulations of IDX184 delivered acceptable levels of 2'-MeG in humans; however, the encapsulation process introduced low levels of the genotoxic impurity ethylene sulfide (ES), which necessitated formulation optimization. Animal pharmacokinetic data guided the development of a tablet with trace levels of ES and pharmacokinetic performance equal to that of the clinical capsule in the monkey. Under fed conditions in humans, the new tablet formulation showed similar exposure to the capsule used in prior clinical trials.

  7. Nuclear weapon testing and the monkey business

    International Nuclear Information System (INIS)

    Murthy, M.S.S.

    1978-01-01

    Reasons for India's total ban on the export of rhesus monkeys to U.S. have been explained. The major reason is that some of the animals were used in nuclear weapon related radiation experiments. This was a clear violation of a stricture in the agreement about supply of monkeys. The stricture prohibited the use of animals for research concerning military operations, including nuclear weapon testing. It is pleaded that a strict enforcement of strictures rather than a total ban on the export of monkeys would be better in the interest of advancement of knowledge in human medicine and disease control. (M.G.B.)

  8. The Monkey game: A computerized verbal working memory task for self-reliant administration in primary school children.

    Science.gov (United States)

    Van de Weijer-Bergsma, Eva; Kroesbergen, Evelyn H; Jolani, Shahab; Van Luit, Johannes E H

    2016-06-01

    In two studies, the psychometric properties of an online self-reliant verbal working memory task (the Monkey game) for primary school children (6-12 years of age) were examined. In Study 1, children (n = 5,203) from 31 primary schools participated. The participants completed computerized verbal and visual-spatial working memory tasks (i.e., the Monkey game and the Lion game) and a paper-and-pencil version of Raven's Standard Progressive Matrices. Reading comprehension and math achievement test scores were obtained from the schools. First, the internal consistency of the Monkey game was examined. Second, multilevel modeling was used to examine the effects of classroom membership. Multilevel multivariate regression analysis was used to examine the Monkey game's concurrent relationship with the Lion game and its predictive relationships with reading comprehension and math achievement. Also, age-related differences in performance were examined. In Study 2, the concurrent relationships between the Monkey game and two tester-led computerized working memory tasks were further examined (n = 140). Also, the 1- and 2-year stability of the Monkey game was investigated. The Monkey game showed excellent internal consistency, good concurrent relationships with the other working memory measures, and significant age differences in performance. Performance on the Monkey game was also predictive of subsequent reading comprehension and mathematics performance, even after controlling for individual differences in intelligence. Performance on the Monkey game was influenced by classroom membership. The Monkey game is a reliable and suitable instrument for the online computerized and self-reliant assessment of verbal working memory in primary school children.

  9. Analogical reasoning in a capuchin monkey (Cebus apella).

    Science.gov (United States)

    Kennedy, Erica Hoy; Fragaszy, Dorothy M

    2008-05-01

    Previous evidence has suggested that analogical reasoning (recognizing similarities among object relations when the objects themselves are dissimilar) is limited to humans and apes. This study investigated whether capuchin monkeys (Cebus apella) can use analogical reasoning to solve a 3-dimensional search task. The task involved hiding a food item under 1 of 2 or 3 plastic cups of different sizes and then allowing subjects to search for food hidden under the cup of analogous size in their own set of cups. Four monkeys were exposed to a series of relational matching tasks. If subjects reached criterion on these tasks, they were exposed to relational transfer tasks involving novel stimuli. Three of the monkeys failed to reach criterion on the basic relational matching tasks and therefore were not tested further. One monkey, however, revealed above-chance performance on a series of transfer tasks with 3 novel stimuli. This evidence suggests that contrary to previous arguments, a member of a New World monkey species can solve an analogical problem. PsycINFO Database Record (c) 2008 APA, all rights reserved.

  10. The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Schleif, William A.; Casimiro, Danilo R.; Handt, Larry; Chen, Minchun; Davies, Mary-Ellen; Liang Xiaoping; Fu Tongming; Tang Aimin; Wilson, Keith A.; McElhaugh, Michael; Carella, Anthony; Tan, Charles; Connolly, Brett; Hill, Susan; Klein, Hilton; Emini, Emilio A.; Shiver, John W.

    2004-01-01

    Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4 + T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection

  11. Long-term effects of neonatal medial temporal ablations on socioemotional behavior in monkeys

    Science.gov (United States)

    Málková, Ludise; Mishkin, Mortimer; Suomi, Stephen J.; Bachevalier, Jocelyne

    2010-01-01

    Socioemotional abnormalities, including low levels of social interaction and high levels of self-directed activity, were reported when rhesus monkeys with neonatal ablations of either the medial temporal lobe (AH) or the inferior temporal cortex (TE) were paired with unoperated peers at two and six months of age, though these abnormalities were more severe in the AH group (Bachevalier et al., 2001). As they reached adulthood (Experiment 1), the same monkeys were re-evaluated in the same dyads and their reactivity to novel toys, social status, and reactions to separation from age-matched peers were also assessed. Group TE now showed few if any of the abnormal behaviors observed when they were infants. By contrast, Group AH continued to display low levels of social interaction, high levels of self-directed activity and submissive behavior, and reduced responses to separation, although they reacted normally to novel toys. To determine whether this degree of socioemotional impairment was less severe than that produced by the same damage in adulthood, we assessed dyadic social interactions of monkeys raised until adulthood in laboratory conditions similar to those of the earlier groups and then given the AH ablation (Experiment 2). Two months postoperatively these adult-lesioned monkeys showed a small reduction in social interactions that became more pronounced six months postoperatively, yet remained less severe than that seen in the infant-lesioned monkeys. Also, except for an increase in food and water consumption throughout this 6-month period, they showed no other socioemotional effects. The finding that neonatal AH lesions produce more severe socioemotional disturbances than the same lesion in adulthood is the reverse of the effect commonly reported for other cognitive functions after cerebral damage. PMID:21133531

  12. Experimental infection of macaques with a wild water bird-derived highly pathogenic avian influenza virus (H5N1.

    Directory of Open Access Journals (Sweden)

    Tomoko Fujiyuki

    Full Text Available Highly pathogenic avian influenza virus (HPAIV continues to threaten human health. Non-human primate infection models of human influenza are desired. To establish an animal infection model with more natural transmission and to determine the pathogenicity of HPAIV isolated from a wild water bird in primates, we administered a Japanese isolate of HPAIV (A/whooper swan/Hokkaido/1/2008, H5N1 clade 2.3.2.1 to rhesus and cynomolgus monkeys, in droplet form, via the intratracheal route. Infection of the lower and upper respiratory tracts and viral shedding were observed in both macaques. Inoculation of rhesus monkeys with higher doses of the isolate resulted in stronger clinical symptoms of influenza. Our results demonstrate that HPAIV isolated from a water bird in Japan is pathogenic in monkeys by experimental inoculation, and provide a new method for HPAIV infection of non-human primate hosts, a good animal model for investigation of HPAIV pathogenicity.

  13. Distribution and abundance of sacred monkeys in Igboland, southern Nigeria.

    Science.gov (United States)

    Baker, Lynne R; Tanimola, Adebowale A; Olubode, Oluseun S; Garshelis, David L

    2009-07-01

    Although primates are hunted on a global scale, some species are protected against harassment and killing by taboos or religious doctrines. Sites where the killing of sacred monkeys or the destruction of sacred groves is forbidden may be integral to the conservation of certain species. In 2004, as part of a distribution survey of Sclater's guenon (Cercopithecus sclateri) in southern Nigeria, we investigated reports of sacred monkeys in the Igbo-speaking region of Nigeria. We confirmed nine new sites where primates are protected as sacred: four with tantalus monkeys (Chlorocebus tantalus) and five with mona monkeys (Cercopithecus mona). During 2004-2006, we visited two communities (Akpugoeze and Lagwa) previously known to harbor sacred populations of Ce. sclateri to estimate population abundance and trends. We directly counted all groups and compared our estimates with previous counts when available. We also estimated the size of sacred groves and compared these with grove sizes reported in the literature. The mean size of the sacred groves in Akpugoeze (2.06 ha, n = 10) was similar to others in Africa south of the Sahel, but larger than the average grove in Lagwa (0.49 ha, n = 15). We estimated a total population of 124 Sclater's monkeys in 15 groups in Lagwa and 193 monkeys in 20 groups in Akpugoeze. The Akpugoeze population was relatively stable over two decades, although the proportion of infants declined, and the number of groups increased. As Sclater's monkey does not occur in any official protected areas, sacred populations are important to the species' long-term conservation. Despite the monkeys' destruction of human crops, most local people still adhere to the custom of not killing monkeys. These sites represent ideal locations in which to study the ecology of Sclater's monkey and human-wildlife interactions. (c) 2009 Wiley-Liss, Inc.

  14. Antigenic analysis of the major structural protein of the Mason-Pfizer monkey virus

    International Nuclear Information System (INIS)

    Schochetman, G.; Boehm-Truitt, M.; Schlom, J.

    1976-01-01

    The major internal protein, p27 (m.w. 27,000 daltons) of the Mason-Pfizer monkey virus (MPMV) was purified by gel filtration and ion-exchange chromatography and then used to develop a radioimmunoassay (RIA). This RIA was specific for MPMV because no immunologic cross-reactivity was observed between p27 of MPMV and 13 different RNA tumor viruses of mammalian and avian origin. However, the p27 of MPMV grown in three different primate cells exhibited identical antigenic cross-reactivity. In addition, significant levels of p27 were found only in MPMV-infected cells. These results indicate that synthesis of p27 is induced after virus infection and that p27 represents a viral-coded protein

  15. Locomotor Anatomy and Behavior of Patas Monkeys (Erythrocebus patas with Comparison to Vervet Monkeys (Cercopithecus aethiops

    Directory of Open Access Journals (Sweden)

    Adrienne L. Zihlman

    2013-01-01

    Full Text Available Patas monkeys (Erythrocebus patas living in African savanna woodlands and grassland habitats have a locomotor system that allows them to run fast, presumably to avoid predators. Long fore- and hindlimbs, long foot bones, short toes, and a digitigrade foot posture were proposed as anatomical correlates with speed. In addition to skeletal proportions, soft tissue and whole body proportions are important components of the locomotor system. To further distinguish patas anatomy from other Old World monkeys, a comparative study based on dissection of skin, muscle, and bone from complete individuals of patas and vervet monkeys (Cercopithecus aethiops was undertaken. Analysis reveals that small adjustments in patas skeletal proportions, relative mass of limbs and tail, and specific muscle groups promote efficient sagittal limb motion. The ability to run fast is based on a locomotor system adapted for long distance walking. The patas’ larger home range and longer daily range than those of vervets give them access to highly dispersed, nutritious foods, water, and sleeping trees. Furthermore, patas monkeys have physiological adaptations that enable them to tolerate and dissipate heat. These features all contribute to the distinct adaptation that is the patas monkeys’ basis for survival in grassland and savanna woodland areas.

  16. Validation of an auditory sensory reinforcement paradigm: Campbell's monkeys (Cercopithecus campbelli) do not prefer consonant over dissonant sounds.

    Science.gov (United States)

    Koda, Hiroki; Basile, Muriel; Olivier, Marion; Remeuf, Kevin; Nagumo, Sumiharu; Blois-Heulin, Catherine; Lemasson, Alban

    2013-08-01

    The central position and universality of music in human societies raises the question of its phylogenetic origin. One of the most important properties of music involves harmonic musical intervals, in response to which humans show a spontaneous preference for consonant over dissonant sounds starting from early human infancy. Comparative studies conducted with organisms at different levels of the primate lineage are needed to understand the evolutionary scenario under which this phenomenon emerged. Although previous research found no preference for consonance in a New World monkey species, the question remained opened for Old World monkeys. We used an experimental paradigm based on a sensory reinforcement procedure to test auditory preferences for consonant sounds in Campbell's monkeys (Cercopithecus campbelli campbelli), an Old World monkey species. Although a systematic preference for soft (70 dB) over loud (90 dB) control white noise was found, Campbell's monkeys showed no preference for either consonant or dissonant sounds. The preference for soft white noise validates our noninvasive experimental paradigm, which can be easily reused in any captive facility to test for auditory preferences. This would suggest that human preference for consonant sounds is not systematically shared with New and Old World monkeys. The sensitivity for harmonic musical intervals emerged probably very late in the primate lineage.

  17. Enhanced replication of damaged SV40 DNA in carcinogen-treated monkey cells

    International Nuclear Information System (INIS)

    Maga, J.A.; Dixon, K.

    1984-01-01

    Treatment of mammalian cells with certain chemical or physical carcinogens prior to infection with ultraviolet-irradiated virus results in enhanced survival or reactivation of the damaged virus. To investigate the molecular basis of this enhanced reactivation (ER), Simian virus 40 DNA replication in carcinogen-treated cells was examined. Treatment of monkey kidney cells with N-acetoxy-2-acetylamino-fluorene or UV radiation 24 h prior to infection with ultraviolet-irradiated Simian virus 40 leads to enhancement of viral DNA replication measured at 36 h after infection by [ 3 H]thymidine incorporation or hybridization. The enhancement of DNA replication is observed when cells are treated from 1 to 60 h before infection or 1 to 16 h after infection. The fact that enhancement is observed also when cells are treated after infection rules out the possiblity that enhancement occurs at the level of adsorption or penetration of the virus. Measurements of the time course of viral DNA replication indicate that pretreatment of cells does not alter the time of onset of viral DNA replication. It is concluded that ER of Simain virus 40 occurs at the level of viral DNA replication. (author)

  18. No effects of dioxin singly on limb malformations in macaque monkeys through epidemiological and treated studies

    Energy Technology Data Exchange (ETDEWEB)

    Asaoka, Kazuo; Iida, Hiroko [Kyoto Univ. (Japan). Primate Research Insitute, Dept. of Molecular and Cellular Biochemistry; Watanabe, Kunio [Kyoto Univ. (Japan). Primate Research Institute, Field Research Center; Goda, Hiroshi [Towa Kagaku Co., Ltd. (Japan); Ihara, Toshio; Nagata, Ryoichi [Shin Nippon Biomedical Laboratories, Ltd. (Japan). Safety Research Facility; Yasuda, Mineo [Hiroshima International Univ. (Japan). Fac. of Health Sciences, Dept. of Clinical Engineering; Kubata, Shunichiro [Tokyo Univ. (Japan). Dept. of Life Science, Graduate School of Arts and Sciences

    2004-09-15

    Human populations exposed with highly dioxin were suspected to be caused immunological dysfunctions, carcinogenesis, and developmental and reproductive dysfunctions. Because of species resemblances, the dioxin effects have been investigating using monkeys as a model for assessment of dioxin exposure on human health. Since 1957 the limb malformations of monkeys in Japan have been reported. The higher frequency of them was found in provisional groups of monkeys who were given the same kind of food for human. The chromosomal abnormalities are excluded from the factor for the congenital limb malformations that are still producing in Japan. In this study, the relations between dioxin and the limb malformations of macaque monkeys were estimated by the epidemiological and administered researches. The dioxin levels in monkeys were measured at two districts that one has the provisional groups including monkeys with limb malformations and the other has breeding groups never seeing the malformations for a long time. TEQ was calculated by the levels of dioxin isomers in the monkeys and the values show no difference between the two places and between the individuals with and without the limb malformations. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered via subcutaneous to pregnant rhesus monkeys from the day 20 of gestation to the day 90 after birth. The exposed babies, including the offspring and died in neonatal, had observed normal limbs in the range of 30-300 ng TCDD /kg of body weight.

  19. On the nature of directed behavior to drug-associated light cues in rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Reilly, Mark P; Berndt, Sonja I; Woods, James H

    2016-11-01

    The present study investigated the role of drug-paired stimuli in controlling the behavior of rhesus monkeys. Systematic observations were made with nine monkeys who had a history of drug self-administration; they had been lever pressing to produce intravenous infusions of various drugs. These observations revealed that the stimulus light co-occurring with drug infusion produced robust and cue-directed behavior such as orienting, touching and biting. Experiment 1 showed that this light-directed behavior would occur in naïve monkeys exposed to a Pavlovian pairing procedure. Four monkeys were given response-independent injections of cocaine. In two monkeys, a red light preceded cocaine injections by 5 s, and a green light co-occurred with the 5-s cocaine injections. In the other two monkeys, the light presentations and cocaine injections occurred independently. Light-directed behavior occurred in all four monkeys within the first couple of trials and at high levels but decreased across sessions. The cocaine-paired stimulus maintained behavior longer and at higher levels than the uncorrelated stimuli. Furthermore, light-directed behavior was not maintained when cocaine was replaced with saline. Light-directed behavior did not occur in the absence of the lights. When these monkeys were subsequently trained to lever press for cocaine, light-directed behavior increased to levels higher than previously observed. Behavior directed towards drug-paired stimuli is robust, reliable and multiply determined; the mechanisms underlying this activity likely include Pavlovian conditioning, stimulus novelty, habituation and operant conditioning.

  20. Default Mode of Brain Function in Monkeys

    Science.gov (United States)

    Mantini, Dante; Gerits, Annelis; Nelissen, Koen; Durand, Jean-Baptiste; Joly, Olivier; Simone, Luciano; Sawamura, Hiromasa; Wardak, Claire; Orban, Guy A.; Buckner, Randy L.; Vanduffel, Wim

    2013-01-01

    Human neuroimaging has revealed a specific network of brain regions—the default-mode network (DMN)—that reduces its activity during goal-directed behavior. So far, evidence for a similar network in monkeys is mainly indirect, since, except for one positron emission tomography study, it is all based on functional connectivity analysis rather than activity increases during passive task states. Here, we tested whether a consistent DMN exists in monkeys using its defining property. We performed a meta-analysis of functional magnetic resonance imaging data collected in 10 awake monkeys to reveal areas in which activity consistently decreases when task demands shift from passive tasks to externally oriented processing. We observed task-related spatially specific deactivations across 15 experiments, implying in the monkey a functional equivalent of the human DMN. We revealed by resting-state connectivity that prefrontal and medial parietal regions, including areas 9/46d and 31, respectively, constitute the DMN core, being functionally connected to all other DMN areas. We also detected two distinct subsystems composed of DMN areas with stronger functional connections between each other. These clusters included areas 24/32, 8b, and TPOC and areas 23, v23, and PGm, respectively. Such a pattern of functional connectivity largely fits, but is not completely consistent with anatomical tract tracing data in monkeys. Also, analysis of afferent and efferent connections between DMN areas suggests a multisynaptic network structure. Like humans, monkeys increase activity during passive epochs in heteromodal and limbic association regions, suggesting that they also default to internal modes of processing when not actively interacting with the environment. PMID:21900574

  1. Captive spider monkeys (Ateles geoffroyi) arm-raise to solicit allo-grooming.

    Science.gov (United States)

    Scheel, Matthew H; Edwards, Dori

    2012-03-01

    Old World monkeys solicit allo-grooming from conspecifics. However, there are relatively few studies of allo-grooming among spider monkeys, and descriptions of allo-grooming solicitation among spider monkeys are anecdotal. In this study, eighty-one hours of video, shot over eight weeks, captured 271 allo-grooming bouts among small groups of captive spider monkeys. Six of eight monkeys made heretofore unreported arm-raises that solicited higher than normal rates of allo-grooming. Allo-grooming bout durations following arm-raises also tended to be longer than bouts not preceded by arm-raises. The efficacy of the arm-raise at soliciting allo-grooming suggests spider monkeys are capable of intentional communication. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Easy rider: monkeys learn to drive a wheelchair to navigate through a complex maze.

    Science.gov (United States)

    Etienne, Stephanie; Guthrie, Martin; Goillandeau, Michel; Nguyen, Tho Hai; Orignac, Hugues; Gross, Christian; Boraud, Thomas

    2014-01-01

    The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in real world environments. There is some incertitude, however, regarding the extrapolation of rodent spatial navigation strategies to primates. Here we present an entirely new platform for investigating real spatial navigation in rhesus monkeys. We showed that monkeys can learn a pathway by using different strategies. In these experiments three monkeys learned to drive the wheelchair and to follow a specified route through a real maze. After learning the route, probe tests revealed that animals successively use three distinct navigation strategies based on i) the place of the reward, ii) the direction taken to obtain reward or iii) a cue indicating reward location. The strategy used depended of the options proposed and the duration of learning. This study reveals that monkeys, like rodents and humans, switch between different spatial navigation strategies with extended practice, implying well-conserved brain learning systems across different species. This new task with freely driving monkeys provides a good support for the electrophysiological and pharmacological investigation of spatial navigation in the real world by making possible electrophysiological and pharmacological investigations.

  3. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    International Nuclear Information System (INIS)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-01-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production

  4. Monkey Business

    Science.gov (United States)

    Blackwood, Christine Horvatis

    2012-01-01

    A ballerina, a gladiator, a camper, a baseball player, a surfer, and a shopper; these are just a few of the amazing monkeys that the author's seventh graders created from papier-mache. This project provided an opportunity for students to express themselves through the creation of sculptural characters based on their own interests, hobbies, and…

  5. Functional analysis of aldehyde oxidase using expressed chimeric enzyme between monkey and rat.

    Science.gov (United States)

    Itoh, Kunio; Asakawa, Tasuku; Hoshino, Kouichi; Adachi, Mayuko; Fukiya, Kensuke; Watanabe, Nobuaki; Tanaka, Yorihisa

    2009-01-01

    Aldehyde oxidase (AO) is a homodimer with a subunit molecular mass of approximately 150 kDa. Each subunit consists of about 20 kDa 2Fe-2S cluster domain storing reducing equivalents, about 40 kDa flavine adenine dinucleotide (FAD) domain and about 85 kDa molybdenum cofactor (MoCo) domain containing a substrate binding site. In order to clarify the properties of each domain, especially substrate binding domain, chimeric cDNAs were constructed by mutual exchange of 2Fe-2S/FAD and MoCo domains between monkey and rat. Chimeric monkey/rat AO was referred to one with monkey type 2Fe-2S/FAD domains and a rat type MoCo domain. Rat/monkey AO was vice versa. AO-catalyzed 2-oxidation activities of (S)-RS-8359 were measured using the expressed enzyme in Escherichia coli. Substrate inhibition was seen in rat AO and chimeric monkey/rat AO, but not in monkey AO and chimeric rat/monkey AO, suggesting that the phenomenon might be dependent on the natures of MoCo domain of rat. A biphasic Eadie-Hofstee profile was observed in monkey AO and chimeric rat/monkey AO, but not rat AO and chimeric monkey/rat AO, indicating that the biphasic profile might be related to the properties of MoCo domain of monkey. Two-fold greater V(max) values were observed in monkey AO than in chimeric rat/monkey AO, and in chimeric monkey/rat AO than in rat AO, suggesting that monkey has the more effective electron transfer system than rat. Thus, the use of chimeric enzymes revealed that 2Fe-2S/FAD and MoCo domains affect the velocity and the quantitative profiles of AO-catalyzed (S)-RS-8359 2-oxidation, respectively.

  6. High Expression of UGT1A1/1A6 in Monkey Small Intestine: Comparison of Protein Expression Levels of Cytochromes P450, UDP-Glucuronosyltransferases, and Transporters in Small Intestine of Cynomolgus Monkey and Human.

    Science.gov (United States)

    Akazawa, Takanori; Uchida, Yasuo; Miyauchi, Eisuke; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

    2018-01-02

    Cynomolgus monkeys have been widely used for the prediction of drug absorption in humans. The purpose of this study was to clarify the regional protein expression levels of cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UGTs), and transporters in small intestine of cynomolgus monkey using liquid chromatography-tandem mass spectrometry, and to compare them with the corresponding levels in human. UGT1A1 in jejunum and ileum were >4.57- and >3.11-fold and UGT1A6 in jejunum and ileum were >16.1- and >8.57-fold, respectively, more highly expressed in monkey than in human. Also, jejunal expression of monkey CYP3A8 (homologue of human CYP3A4) was >3.34-fold higher than that of human CYP3A4. Among apical drug efflux transporters, BCRP showed the most abundant expression in monkey and human, and the expression levels of BCRP in monkey and human were >1.74- and >1.25-fold greater than those of P-gp and >2.76- and >4.50-fold greater than those of MRP2, respectively. These findings should be helpful to understand species differences of the functions of CYPs, UGTs, and transporters between monkey and human. The UGT1A1/1A6 data would be especially important because it is difficult to identify isoforms responsible for species differences of intestinal glucuronidation by means of functional studies due to overlapping substrate specificity.

  7. Evaluation of monkey intraocular pressure by rebound tonometer

    Science.gov (United States)

    Yu, Wenhan; Cao, Guiqun; Qiu, Jinghua; Ma, Jia; Li, Ni; Yu, Man; Yan, Naihong; Chen, Lei; Pang, Iok-Hou

    2009-01-01

    Purpose To evaluate the usefulness of the TonoVet™ rebound tonometer in measuring intraocular pressure (IOP) of monkeys. Methods The accuracy of the TonoVet™ rebound tonometer was determined in cannulated eyes of anesthetized rhesus monkeys where IOP was controlled by adjusting the height of a connected perfusate reservoir. To assess the applicability of the equipment through in vivo studies, the diurnal fluctuation of IOP and effects of IOP-lowering compounds were evaluated in monkeys. Results IOP readings generated by the TonoVet™ tonometer correlated very well with the actual pressure in the cannulated monkey eye. The linear correlation had a slope of 0.922±0.014 (mean±SEM, n=4), a y-intercept of 3.04±0.61, and a correlation coefficient of r2=0.97. Using this method, diurnal IOP fluctuation of the rhesus monkey was demonstrated. The tonometer was also able to detect IOP changes induced by pharmacologically active compounds. A single topical ocular instillation (15 μg) of the rho kinase inhibitor, H1152, produced a 5–6 mmHg reduction (pmonkey eye. PMID:19898690

  8. Computing Arm Movements with a Monkey Brainet.

    Science.gov (United States)

    Ramakrishnan, Arjun; Ifft, Peter J; Pais-Vieira, Miguel; Byun, Yoon Woo; Zhuang, Katie Z; Lebedev, Mikhail A; Nicolelis, Miguel A L

    2015-07-09

    Traditionally, brain-machine interfaces (BMIs) extract motor commands from a single brain to control the movements of artificial devices. Here, we introduce a Brainet that utilizes very-large-scale brain activity (VLSBA) from two (B2) or three (B3) nonhuman primates to engage in a common motor behaviour. A B2 generated 2D movements of an avatar arm where each monkey contributed equally to X and Y coordinates; or one monkey fully controlled the X-coordinate and the other controlled the Y-coordinate. A B3 produced arm movements in 3D space, while each monkey generated movements in 2D subspaces (X-Y, Y-Z, or X-Z). With long-term training we observed increased coordination of behavior, increased correlations in neuronal activity between different brains, and modifications to neuronal representation of the motor plan. Overall, performance of the Brainet improved owing to collective monkey behaviour. These results suggest that primate brains can be integrated into a Brainet, which self-adapts to achieve a common motor goal.

  9. Effective treatment with a tetrandrine/chloroquine combination for chloroquine-resistant falciparum malaria in Aotus monkeys

    Science.gov (United States)

    2013-01-01

    Background In vitro evidence indicates that tetrandrine (TT) can potentiate the action of chloroquine 40-fold against choloquine-resistant Plasmodium falciparum. The key question emanating from that study is “would tetrandine and chloroquine be highly effective in a live Aotus monkey model with chloroquine-resistant parasites”. This study was designed to closely mimic the pharmacological/anti-malarial activity in man. Methods The Vietnam Smith/RE strain of P. falciparum, which is chloroquine-resistant was used in this study. Previous experimental procedures were followed. Panamanian owl monkeys (Aotus) were inoculated with 5×106 erythrocytes parasitized with the CQ-resistant strain of P. falciparum. Oral drug treatment was with CQ (20 mg/kg) and/or tetrandrine at 15 mg/Kg, 30 mg/Kg or 60 mg/Kg or 25 mg/Kg depending on experimental conditions. Results and Discussion Parasitaemia was cleared rapidly with CQ and TT while CQ treatment alone was ineffective. Recrudescence of malaria occurred after seven days post-infection. However, four animals were treated orally with TT and CQ parasites were cleared. It is likely that monkeys were cured via a combination of both drug and host immune responses. A single Aotus monkey infected with P. falciparum and untreated with drugs, died. No side effects were observed with these drug treatments. Conclusions This combination of chloroquine and tetrandrine forms the basis of a new attack on chloroquine-resistant malaria - one based upon inhibition of the basis of chloroquine resistance, the multiple drug resistance pump. Previous studies demonstrated that the parasite MDR pump was found on parasite membranes using 3H azidopine photoaffinity labelling. Since MDR-based choloroquine resistance is induced by chloroquine, the basis of the action of tetrandrine is the following: 1) tetrandrine inhibits the MDR pump by stimulating MDR ATPase which limits the energy of the pump by depletion of parasite ATP, 2) tetrandrine blocks the

  10. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  11. Tufted capuchin monkeys (Sapajus sp) learning how to crack nuts: does variability decline throughout development?

    Science.gov (United States)

    Resende, Briseida Dogo; Nagy-Reis, Mariana Baldy; Lacerda, Fernanda Neves; Pagnotta, Murillo; Savalli, Carine

    2014-11-01

    We investigated the process of nut-cracking acquisition in a semi-free population of tufted capuchin monkeys (Sapajus sp) in São Paulo, Brazil. We analyzed the cracking episodes from monkeys of different ages and found that variability of actions related to cracking declined. Inept movements were more frequent in juveniles, which also showed an improvement on efficient striking. The most effective behavioral sequence for cracking was more frequently used by the most experienced monkeys, which also used non-optimal sequences. Variability in behavior sequences and actions may allow adaptive changes to behavior under changing environmental conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Multiple roles of the coagulation protease cascade during virus infection.

    Science.gov (United States)

    Antoniak, Silvio; Mackman, Nigel

    2014-04-24

    The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

  13. Piracetam-induced changes on the brainstem auditory response in anesthetized juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases.

    Science.gov (United States)

    Durand-Rivera, A; Gonzalez-Pina, R; Hernandez-Godinez, B; Ibanez-Contreras, A; Bueno-Nava, A; Alfaro-Rodriguez, A

    2012-10-01

    We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. In this report, we discuss the significance of these observations. © 2012 John Wiley & Sons A/S.

  14. PUSTULAR DERMATITIS CAUSED BY IMPETIGO IN RED-TAILED MONKEYS ( CERCOPITHECUS ASCANIUS).

    Science.gov (United States)

    Coughlin, Patrick; Bradford, Carol; Montali, Richard J; Bronson, Ellen

    2018-03-01

    Impetigo is a bacterial infection of the superficial layer of the epidermis with crusting or bullae caused by Streptococcus spp., Staphylococcus spp., or both. A 14-yr-old red-tailed monkey ( Cercopithecus ascanius) presented with recurrent scabbing and ulceration under the nares over an 8-yr period. Repeated cultures and biopsy samples led to a presumptive diagnosis of impetigo, later confirmed on necropsy. Multiple antibiotic regimens were employed with varying success during multiple episodes, while lesions resolved on their own at other times. This condition has not been previously reported in a nonhuman primate, although it is not uncommon in humans.

  15. Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

    Science.gov (United States)

    Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

    2001-01-01

    To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

  16. Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1

    Science.gov (United States)

    Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

    2015-01-01

    The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement—there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

  17. Helicobacter pylori SabA Adhesin in Persistent Infection and Chronic Inflammation

    OpenAIRE

    Mahdavi, Jafar; Sondén, Berit; Hurtig, Marina; Olfat, Farzad O.; Forsberg, Lina; Roche, Niamh; Ångström, Jonas; Larsson, Thomas; Teneberg, Susann; Karlsson, Karl-Anders; Altraja, Siiri; Wadström, Torkel; Kersulyte, Dangeruta; Berg, Douglas E.; Dubois, Andre

    2002-01-01

    Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) wa...

  18. A preliminary report on oral fat tolerance test in rhesus monkeys

    OpenAIRE

    Wu, Di; Liu, Qingsu; Wei, Shiyuan; Zhang, Yu Alex; Yue, Feng

    2014-01-01

    Background Oral fat tolerance test (OFTT) has been widely used to assess the postprandial lipemia in human beings, but there is few studies concerning OFTT in nonhuman primates. This study is designed to explore the feasibility of OFTT in rhesus monkeys. Methods In a cross-over study, a total of 8 adult female rhesus monkeys were fed with normal monkey diet (NND), high sugar high fat diet (HHD), and extremely high fat diet (EHD), respectively. Each monkey consumed NND, HHD and EHD respectivel...

  19. Rhesus monkey lens as an in vitro model for studying oxidative stress

    International Nuclear Information System (INIS)

    Zigler, J.S. Jr.; Lucas, V.A.; Du, X.Y.

    1989-01-01

    Lenses from young rhesus monkeys were incubated in the presence of H 2 O 2 or oxygen radical generating systems to determine their suitability as a model for investigating lenticular oxidative stress. Additionally, direct comparisons were made between the effects found with the monkey lenses and those observed with cultured rat lenses exposed to the same oxidizing systems. As in earlier studies with rat lenses the monkey lenses exhibited impaired ability to actively accumulate from the medium radioactively labelled rubidium and choline following exposure to oxidative stress. Based on the effects of various scavengers of oxygen radicals it appeared that the mechanisms responsible for lens damage were the same for both rat and monkey lenses. However, rat lenses were damaged by lower concentrations of oxidants than were monkey lenses. It was concluded that oxidative stress affects both rat and monkey lenses by similar mechanisms but that lenses from monkeys, and probably other primates, are more resistant to these effects because they have better endogenous antioxidant defenses

  20. A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    2017-11-01

    Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

  1. Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys.

    Directory of Open Access Journals (Sweden)

    Wendelien B Oswald

    2007-01-01

    Full Text Available Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.

  2. A case of polymicrogyria in macaque monkey: impact on anatomy and function of the motor system

    Directory of Open Access Journals (Sweden)

    Rouiller Eric M

    2009-12-01

    Full Text Available Abstract Background Polymicrogyria is a malformation of the cerebral cortex often resulting in epilepsy or mental retardation. It remains unclear whether this pathology affects the structure and function of the corticospinal (CS system. The anatomy and histology of the brain of one macaque monkey exhibiting a spontaneous polymicrogyria (PMG monkey were examined and compared to the brain of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA unilaterally in a region where low intensity electrical microstimulation elicited contralateral hand movements (presumably the primary motor cortex in the PMG monkey. Results The examination of the brain showed a large number of microgyri at macro- and microscopic levels, covering mainly the frontoparietal regions. The layered cortical organization was locally disrupted and the number of SMI-32 stained pyramidal neurons in the cortical layer III of the presumed motor cortex was reduced. We compared the distribution of labelled CS axons in the PMG monkey at spinal cervical level C5. The cumulated length of CS axon arbors in the spinal grey matter was not significantly different in the PMG monkey. In the red nucleus, numerous neurons presented large vesicles. We also assessed its motor performances by comparing its capacity to execute a complex reach and grasp behavioral task. The PMG monkey exhibited an increase of reaction time without any modification of other motor parameters, an observation in line with a normal CS tract organisation. Conclusion In spite of substantial cortical malformations in the frontal and parietal lobes, the PMG monkey exhibits surprisingly normal structure and function of the corticospinal system.

  3. Neonatal face-to-face interactions promote later social behaviour in infant rhesus monkeys

    Science.gov (United States)

    Dettmer, Amanda M.; Kaburu, Stefano S. K.; Simpson, Elizabeth A.; Paukner, Annika; Sclafani, Valentina; Byers, Kristen L.; Murphy, Ashley M.; Miller, Michelle; Marquez, Neal; Miller, Grace M.; Suomi, Stephen J.; Ferrari, Pier F.

    2016-01-01

    In primates, including humans, mothers engage in face-to-face interactions with their infants, with frequencies varying both within and across species. However, the impact of this variation in face-to-face interactions on infant social development is unclear. Here we report that infant monkeys (Macaca mulatta) who engaged in more neonatal face-to-face interactions with mothers have increased social interactions at 2 and 5 months. In a controlled experiment, we show that this effect is not due to physical contact alone: monkeys randomly assigned to receive additional neonatal face-to-face interactions (mutual gaze and intermittent lip-smacking) with human caregivers display increased social interest at 2 months, compared with monkeys who received only additional handling. These studies suggest that face-to-face interactions from birth promote young primate social interest and competency. PMID:27300086

  4. Peripheral refraction in normal infant rhesus monkeys

    Science.gov (United States)

    Hung, Li-Fang; Ramamirtham, Ramkumar; Huang, Juan; Qiao-Grider, Ying; Smith, Earl L.

    2008-01-01

    Purpose To characterize peripheral refractions in infant monkeys. Methods Cross-sectional data for horizontal refractions were obtained from 58 normal rhesus monkeys at 3 weeks of age. Longitudinal data were obtained for both the vertical and horizontal meridians from 17 monkeys. Refractive errors were measured by retinoscopy along the pupillary axis and at eccentricities of 15, 30, and 45 degrees. Axial dimensions and corneal power were measured by ultrasonography and keratometry, respectively. Results In infant monkeys, the degree of radial astigmatism increased symmetrically with eccentricity in all meridians. There were, however, initial nasal-temporal and superior-inferior asymmetries in the spherical-equivalent refractive errors. Specifically, the refractions in the temporal and superior fields were similar to the central ametropia, but the refractions in the nasal and inferior fields were more myopic than the central ametropia and the relative nasal field myopia increased with the degree of central hyperopia. With age, the degree of radial astigmatism decreased in all meridians and the refractions became more symmetrical along both the horizontal and vertical meridians; small degrees of relative myopia were evident in all fields. Conclusions As in adult humans, refractive error varied as a function of eccentricity in infant monkeys and the pattern of peripheral refraction varied with the central refractive error. With age, emmetropization occurred for both central and peripheral refractive errors resulting in similar refractions across the central 45 degrees of the visual field, which may reflect the actions of vision-dependent, growth-control mechanisms operating over a wide area of the posterior globe. PMID:18487366

  5. Monkey cortex through fMRI glasses.

    Science.gov (United States)

    Vanduffel, Wim; Zhu, Qi; Orban, Guy A

    2014-08-06

    In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Comment on "Monkey vocal tracts are speech-ready".

    Science.gov (United States)

    Lieberman, Philip

    2017-07-01

    Monkey vocal tracts are capable of producing monkey speech, not the full range of articulate human speech. The evolution of human speech entailed both anatomy and brains. Fitch, de Boer, Mathur, and Ghazanfar in Science Advances claim that "monkey vocal tracts are speech-ready," and conclude that "…the evolution of human speech capabilities required neural change rather than modifications of vocal anatomy." Neither premise is consistent either with the data presented and the conclusions reached by de Boer and Fitch themselves in their own published papers on the role of anatomy in the evolution of human speech or with the body of independent studies published since the 1950s.

  7. Plasmodium vivax thrombospondin related adhesion protein: immunogenicity and protective efficacy in rodents and Aotus monkeys

    Directory of Open Access Journals (Sweden)

    Angélica Castellanos

    2007-06-01

    Full Text Available The thrombospondin related adhesion protein (TRAP is a malaria pre-erythrocytic antigen currently pursued as malaria vaccine candidate to Plasmodium falciparum. In this study, a long synthetic peptide (LSP representing a P. vivax TRAP fragment involved in hepatocyte invasion was formulated in both Freund and Montanide ISA 720 adjutants and administered by IM and subcutaneous routes to BALB/c mice and Aotus monkeys. We measured specific humoral immune responses in both animal species and performed a sporozoite challenge in Aotus monkeys to assess the protective efficacy of the vaccine. After immunization both mice and Aotus seroconverted as shown by ELISA, and the specific anti-peptide antibodies cross reacted with the parasite in IFAT assays. Only two out of six immunized animals became infected after P. vivax sporozoite challenge as compared with four out of six animals from the control group. These results suggest that this TRAP fragment has protective potential against P. vivax malaria and deserves further studies as vaccine candidate.

  8. Untargeted viral mutagenesis is not found in X-irradiated monkey cells

    International Nuclear Information System (INIS)

    Lytle, C.D.; Carney, P.G.; Lee, W.; Bushar, H.F.

    1988-01-01

    The existence of untargeted viral mutagenesis in X-irradiated cells was investigated in a mammalian virus/cell system, where a low level of such viral mutagenesis can be demonstrated in UV-irradiated cells. In the positive control experiment UV-elicited mutagenesis was shown with cell exposures of 5, 10 and 15 J/m 2 and a delay of 24 h between cell irradiation and infection with unirradiated herpes simplex virus. Although X-ray doses of 1, 3 and 10 Gy elicit enhanced reactivation of UV-irradiated virus, no untargeted mutagenesis for any X-ray dose at post-irradiation infection times of 0, 24 or 72 h was observed in this study. Thus untargeted mutagenesis of herpes simplex virus was not demonstrated in X-irradiated monkey cells, under conditions where X-ray-enhanced reactivation occurs and where untargeted mutagenesis in UV-irradiated cells occurs. (author)

  9. Preference transitivity and symbolic representation in capuchin monkeys (Cebus apella.

    Directory of Open Access Journals (Sweden)

    Elsa Addessi

    Full Text Available BACKGROUND: Can non-human animals comprehend and employ symbols? The most convincing empirical evidence comes from language-trained apes, but little is known about this ability in monkeys. Tokens can be regarded as symbols since they are inherently non-valuable objects that acquire an arbitrarily assigned value upon exchange with an experimenter. Recent evidence suggested that capuchin monkeys, which diverged from the human lineage 35 million years ago, can estimate, represent and combine token quantities. A fundamental and open question is whether monkeys can reason about symbols in ways similar to how they reason about real objects. METHODOLOGY/PRINCIPAL FINDINGS: Here we examined this broad question in the context of economic choice behavior. Specifically, we assessed whether, in a symbolic context, capuchins' preferences satisfy transitivity--a fundamental trait of rational decision-making. Given three options A, B and C, transitivity holds true if A > or = B, B > or = C and A > or = C (where > or = indicates preference. In this study, we trained monkeys to exchange three types of tokens for three different foods. We then compared choices monkeys made between different types of tokens with choices monkeys made between the foods. Qualitatively, capuchins' preferences revealed by the way of tokens were similar to those measured with the actual foods. In particular, when choosing between tokens, monkeys displayed strict economic preferences and their choices satisfied transitivity. Quantitatively, however, values measured by the way of tokens differed systematically from those measured with the actual foods. In particular, for any pair of foods, the relative value of the preferred food increased when monkeys chose between the corresponding tokens. CONCLUSIONS/SIGNIFICANCE: These results indicate that indeed capuchins are capable of treating tokens as symbols. However, as they do so, capuchins experience the cognitive burdens imposed by symbolic

  10. Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Martín, Jorge; Bernardo, Lídice; López, Carlos; Niebla, Olivia; Menéndez, Tamara; Romero, Yaremis; Sánchez, Jorge; Guzmán, María G; Guillén, Gerardo

    2010-05-01

    The aim of the present work was to test the concept of the heterologous prime-boost strategy combining an infective dengue virus with a recombinant chimeric protein carrying domain III of the envelope protein. Two studies in monkeys, combining recombinant protein PD5 (domain III of the envelope protein from dengue-2 virus, fused to the protein carrier P64k) and the infective dengue virus in the same immunization schedules were carried out. Humoral and cell-mediated immunity were evaluated. In the first study, monkeys received four doses of the protein PD5 and were subsequently infected with one dose of dengue virus. Antibody response measured after virus inoculation was significantly higher compared to that in non-primed monkeys and comparable to that elicited after two doses of infective virus. In a second study, monkeys were infected with one dose of the virus and subsequently boosted with one dose of the recombinant protein, reaching high levels of neutralizing antibodies, which were still detectable 14 months after the last immunization. In addition, the cellular immune response was also recalled. The results obtained in the present work support the approach of heterologous prime-boosting, in either order prime or boost, combining the chimeric protein PD5 (formulated in alum-CPS-A) and an infective dengue virus. The latter could potentially be replaced by an attenuated vaccine candidate. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Pharmacokinetics and immunogenicity investigation of a human anti-interleukin-17 monoclonal antibody in non-naïve cynomolgus monkeys.

    Science.gov (United States)

    Han, Chao; Gunn, George R; Marini, Joseph C; Shankar, Gopi; Han Hsu, Helen; Davis, Hugh M

    2015-05-01

    The pharmacokinetics (PK) of biologic therapeutics, especially monoclonal antibodies (mAbs), in monkeys generally presents the most relevant predictive PK information for humans. However, human mAbs, xenogeneic proteins to monkeys, are likely to be immunogenic. Monkeys previously treated with a human mAb (non-naïve) may have developed antidrug antibodies (ADAs) that cross-react with another test mAb in subsequent studies. Unlike PK studies for small-molecule therapeutics, in which animals may be reused, naïve monkeys have been used almost exclusively for preclinical PK studies of biologic therapeutics to avoid potential pre-existing immunologic cross-reactivity issues. The propensity and extent of pre-existing ADAs have not been systematically investigated to date. In this study, the PK and immunogenicity of mAb A, a human anti-human interkeukin-17 mAb, were investigated in a colony of 31 cynomolgus monkeys previously exposed to other human mAbs against different targets. We screened the monkeys for pre-existing antibodies to mAb A prior to the PK study and showed that 44% of the monkeys had pre-existing cross-reactive antibodies to mAb A, which could affect the PK characterization of the antibody. In the subcolony of monkeys without measurable pre-existing ADAs, PK and immunogenicity of mAb A were successfully characterized. The impact of ADAs on mAb A PK was also demonstrated in the monkeys with pre-existing ADAs. Here we report the results and propose a pragmatic approach for the use of non-naïve monkeys when conducting PK studies of biologic therapeutics. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Nutrient Intake and Digestibility of Cynomolgus Monkey (Macaca fascicularis Fed with High Soluble Carbohydrate Diet: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    DEWI APRI ASTUTI

    2009-12-01

    Full Text Available High carbohydrate as obese diet is not yet available commercially for monkeys. Therefore, this preliminary study was to carry out nutrient intake and digestibility of cynomolgus monkeys (Macaca fascicularis fed with high soluble carbohydrate diet compared to monkey chow. Five adult female macaques (average body weight 2.67 kg were made to consume freshly diet. Commercial monkey chows (contains 3500 cal/g energy and 35% starch were fed to three adult females (average body weight 3.62 kg. Nutrient intakes and digestibility parameters were measured using modified metabolic cages. Result showed that average of protein, fat, starch, and energy intakes in treatment diet were higher than control diet (T-test. Fat intake in the treatment diet was three times higher, while starch and energy intakes were almost two times higher than monkey chow. Digestibility percentage of all nutrients were the same in both diets except for the protein. The study concludes that the freshly prepared high sugar diet was palatable and digestible for the cynomolgus monkeys. Further studies are in progress to develop obese diet high in energy content based on fat and source of starch treatments.

  13. Dual-isotope single-photon emission computed tomography for dopamine and serotonin transporters in normal and parkinsonian monkey brains

    International Nuclear Information System (INIS)

    Li, I-H.; Huang, W.-S.; Yeh, C.-B.; Liao, M.-H.; Chen, C.-C.; Shen, L.-H.; Liu, J.-C.; Ma, K.-H.

    2009-01-01

    Introduction: Parkinson's disease (PD) affects both dopaminergic and serotonergic systems. In this study, we simultaneously evaluated dopamine and serotonin transporters in primates using dual-isotope single-photon emission computed tomography (SPECT) imaging and compared the results with traditional single-isotope imaging. Methods: Four healthy and one 6-OHDA-induced PD monkeys were used for this study. SPECT was performed over 4 h after individual or simultaneous injection of [ 99m Tc]TRODAT-1 (a dopamine transporter imaging agent) and [ 123 I]ADAM (a serotonin transporter imaging agent). Results: The results showed that the image quality and uptake ratios in different brain regions were comparable between single- and dual-isotope studies. The striatal [ 99m Tc]TRODAT-1 uptake in the PD monkey was markedly lower than that in normal monkeys. The uptake of [ 123 I]ADAM in the midbrain of the PD monkey was comparable to that in the normal monkeys, but there were decreased uptakes in the thalamus and striatum of the PD monkey. Conclusions: Our results suggest that dual-isotope SPECT using [ 99m Tc]TRODAT-1 and [ 123 I]ADAM can simultaneously evaluate changes in dopaminergic and serotonergic systems in a PD model.

  14. Neutrophilic nodules in the intestinal walls of Japanese monkeys associated with the neutrophil chemotactic activity of larval extracts and secretions of Oesophagostomum aculeatum.

    Science.gov (United States)

    Horii, Y; Ishii, A; Owhashi, M; Miyoshi, M; Usui, M

    1985-01-01

    High neutrophil chemotactic activity was detected in the culture medium from Oesophagostomum aculeatum larvae in vitro using blind-well chambers with Millipore filters, and guinea pig leucocytes as indicator cells. Neutrophil chemotactic activity was also detected in the extract from larval worms in a dose dependent fashion. This activity was detected in the low molecular weight fractions adjacent to a sodium chloride marker by gel filtration on Sephadex G200. These results were further confirmed with monkey neutrophils. The possible role of this activity in the formation of granulomatous lesions rich in neutrophils found in O aculeatum infections in the Japanese monkey is discussed.

  15. Evaluation of diabetes determinants in woolly monkeys (Lagothrix lagotricha)

    NARCIS (Netherlands)

    Ange-van Heugten, K.D.; Burns, R.; Verstegen, M.W.A.; Jansen, W.L.; Ferket, P.R.; Heugten, E.

    2007-01-01

    Woolly monkeys (Lagothrix lagotricha) are a threatened specie in the wild with limited successful management in captivity due to diagnosed hypertension and suspected diabetic conditions. Six woolly monkeys with known hypertension problems were tested to determine if diabetes mellitus and current

  16. An Entamoeba sp. strain isolated from rhesus monkey is virulent but genetically different from Entamoeba histolytica.

    Science.gov (United States)

    Tachibana, Hiroshi; Yanagi, Tetsuo; Pandey, Kishor; Cheng, Xun-Jia; Kobayashi, Seiki; Sherchand, Jeevan B; Kanbara, Hiroji

    2007-06-01

    An Entamoeba sp. strain, P19-061405, was isolated from a rhesus monkey in Nepal and characterized genetically. The strain was initially identified as Entamoeba histolytica using PCR amplification of peroxiredoxin genes. However, sequence analysis of the 18S rRNA gene showed a 0.8% difference when compared to the reference E. histolytica HM-1:IMSS human strain. Differences were also observed in the 5.8S rRNA gene and the internal transcribed spacer (ITS) regions 1 and 2, and analysis of the serine-rich protein gene from the monkey strain showed unique codon usages compared to E. histolytica isolated from humans. The amino acid sequences of two hexokinases and two glucose phosphate isomerases also differed from those of E. histolytica. Isoenzyme analyses of these enzymes in the monkey strain showed different electrophoretic mobility patterns compared with E. histolytica isolates. Analysis of peroxiredoxin genes indicated the presence of at least seven different types of protein, none of which were identical to proteins in E. histolytica. When the trophozoites from the monkey strain were inoculated into the livers of hamsters, formation of amebic abscesses was observed 7 days after the injection. These results demonstrate that the strain is genetically different from E. histolytica and is virulent. Revival of the name Entamoeba nuttalli is proposed for the organism.

  17. Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella spp.

    OpenAIRE

    Oaks, E V; Hale, T L; Formal, S B

    1986-01-01

    The serum antibody response to proteins encoded by the virulence-associated plasmid of Shigella flexneri was determined in monkeys challenged with virulent S. flexneri serotype 2a. With water-extractable antigen in an enzyme-linked immunosorbent assay, a significant increase in antibody titer against proteins from a plasmid-carrying, virulent strain of S. flexneri serotype 5 could be demonstrated in convalescent sera. There were minimal antibody titers against proteins from an avirulent (plas...

  18. In vivo tomographic study of cerebral blood perfusion with SPECT in hemiparkinsonian monkeys

    International Nuclear Information System (INIS)

    Chen Shengdi; Xu Delong

    1994-01-01

    The authors present data on the utility of functional brain imaging with 99m Tc-ECD and SPECT in the study of MPTP induced hemiparkinsonism in monkeys. Injection of MPTP into the right common carotid artery of 10 rhesus monkeys produced hemiparkinsonism in the contralateral limbs which responded to antiparkinsonian medication. The unilateral neurotoxicity of the MPTP treated side was confirmed biochemically by marked reduction of DA contents in the nigrostriatum and histologically by selective neuronal loss in the substantia nigra. These monkeys with hemiparkinsonism were studied with SPECT using 99m Tc-ECD as perfusion marker. The results of brain scanning showed that the cerebral blood perfusion of MPTP treated side was significantly depleted 20∼90 days after MPTP intoxication, and returned to normal 8 months after perfusion. The experiment indicates that abnormal cerebral blood perfusion is involved in the course of parkinsonian pathophysiology

  19. Intrapericardial Denervation: Responses to Water Immersion in Rhesus Monkeys

    Science.gov (United States)

    McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold

    1995-01-01

    Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

  20. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

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

    2015-02-18

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

  1. Fast optical signal not detected in awake behaving monkeys.

    Science.gov (United States)

    Radhakrishnan, Harsha; Vanduffel, Wim; Deng, Hong Ping; Ekstrom, Leeland; Boas, David A; Franceschini, Maria Angela

    2009-04-01

    While the ability of near-infrared spectroscopy (NIRS) to measure cerebral hemodynamic evoked responses (slow optical signal) is well established, its ability to measure non-invasively the 'fast optical signal' is still controversial. Here, we aim to determine the feasibility of performing NIRS measurements of the 'fast optical signal' or Event-Related Optical Signals (EROS) under optimal experimental conditions in awake behaving macaque monkeys. These monkeys were implanted with a 'recording well' to expose the dura above the primary visual cortex (V1). A custom-made optical probe was inserted and fixed into the well. The close proximity of the probe to the brain maximized the sensitivity to changes in optical properties in the cortex. Motion artifacts were minimized by physical restraint of the head. Full-field contrast-reversing checkerboard stimuli were presented to monkeys trained to perform a visual fixation task. In separate sessions, two NIRS systems (CW4 and ISS FD oximeter), which previously showed the ability to measure the fast signal in human, were used. In some sessions EEG was acquired simultaneously with the optical signal. The increased sensitivity to cortical optical changes with our experimental setup was quantified with 3D Monte Carlo simulations on a segmented MRI monkey head. Averages of thousands of stimuli in the same animal, or grand averages across the two animals and across repeated sessions, did not lead to detection of the fast optical signal using either amplitude or phase of the optical signal. Hemodynamic responses and visual evoked potentials were instead always detected with single trials or averages of a few stimuli. Based on these negative results, despite the optimal experimental conditions, we doubt the usefulness of non-invasive fast optical signal measurements with NIRS.

  2. A deficit in face-voice integration in developing vervet monkeys exposed to ethanol during gestation.

    Directory of Open Access Journals (Sweden)

    Shahin Zangenehpour

    Full Text Available Children with fetal alcohol spectrum disorders display behavioural and intellectual impairments that strongly implicate dysfunction within the frontal cortex. Deficits in social behaviour and cognition are amongst the most pervasive outcomes of prenatal ethanol exposure. Our naturalistic vervet monkey model of fetal alcohol exposure (FAE provides an unparalleled opportunity to study the neurobehavioral outcomes of prenatal ethanol exposure in a controlled experimental setting. Recent work has revealed a significant reduction of the neuronal population in the frontal lobes of these monkeys. We used an intersensory matching procedure to investigate audiovisual perception of socially relevant stimuli in young FAE vervet monkeys. Here we show a domain-specific deficit in audiovisual integration of socially relevant stimuli. When FAE monkeys were shown a pair of side-by-side videos of a monkey concurrently presenting two different calls along with a single audio track matching the content of one of the calls, they were not able to match the correct video to the single audio track. This was manifest by their average looking time being equally spent towards both the matching and non-matching videos. However, a group of normally developing monkeys exhibited a significant preference for the non-matching video. This inability to integrate and thereby discriminate audiovisual stimuli was confined to the integration of faces and voices as revealed by the monkeys' ability to match a dynamic face to a complex tone or a black-and-white checkerboard to a pure tone, presumably based on duration and/or onset-offset synchrony. Together, these results suggest that prenatal ethanol exposure negatively affects a specific domain of audiovisual integration. This deficit is confined to the integration of information that is presented by the face and the voice and does not affect more elementary aspects of sensory integration.

  3. A deficit in face-voice integration in developing vervet monkeys exposed to ethanol during gestation.

    Science.gov (United States)

    Zangenehpour, Shahin; Javadi, Pasha; Ervin, Frank R; Palmour, Roberta M; Ptito, Maurice

    2014-01-01

    Children with fetal alcohol spectrum disorders display behavioural and intellectual impairments that strongly implicate dysfunction within the frontal cortex. Deficits in social behaviour and cognition are amongst the most pervasive outcomes of prenatal ethanol exposure. Our naturalistic vervet monkey model of fetal alcohol exposure (FAE) provides an unparalleled opportunity to study the neurobehavioral outcomes of prenatal ethanol exposure in a controlled experimental setting. Recent work has revealed a significant reduction of the neuronal population in the frontal lobes of these monkeys. We used an intersensory matching procedure to investigate audiovisual perception of socially relevant stimuli in young FAE vervet monkeys. Here we show a domain-specific deficit in audiovisual integration of socially relevant stimuli. When FAE monkeys were shown a pair of side-by-side videos of a monkey concurrently presenting two different calls along with a single audio track matching the content of one of the calls, they were not able to match the correct video to the single audio track. This was manifest by their average looking time being equally spent towards both the matching and non-matching videos. However, a group of normally developing monkeys exhibited a significant preference for the non-matching video. This inability to integrate and thereby discriminate audiovisual stimuli was confined to the integration of faces and voices as revealed by the monkeys' ability to match a dynamic face to a complex tone or a black-and-white checkerboard to a pure tone, presumably based on duration and/or onset-offset synchrony. Together, these results suggest that prenatal ethanol exposure negatively affects a specific domain of audiovisual integration. This deficit is confined to the integration of information that is presented by the face and the voice and does not affect more elementary aspects of sensory integration.

  4. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures.

    Science.gov (United States)

    Someswara Rao, Chinta; Viswanadha Raju, S

    2016-03-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship between the H. sapiens and monkey. This similarity will be helpful at theft identification, maternity identification, disease identification, etc.

  5. γ-Ray-induced reciprocal translocations in spermatogonia of the crab-eating monkey (Macaca fascicularis)

    International Nuclear Information System (INIS)

    Matsuda, Y.; Tobari, I.; Yamagiwa, J.; Utsugi, T.; Kitazume, M.; Nakai, S.

    1984-01-01

    The yield of translocations induced by γ-rays in the crab-eating monkey (Macaca fascicularis) spermatogonia were studied by cytological analysis in spermatocytes derived from them. The frequencies of translocations were 0.09 per cent at 0 Gy, 1.9 per cent at 1 Gy, 2.5 per cent at 2 Gy and 1.3 per cent at 3 Gy, showing a humped dose-response curve with a peak yield around 2 Gy. No remarkable inter-seasonal or inter-animal variations in the induction of translocation were observed. The frequencies in the crab-eating monkey were significantly higher than those in the same Macaca genus, the rhesus monkey (Macaca mulatta). This inter-species difference in radiosensitivity might be affected by the condition of spermatogonial stem cells at the time of exposure to radiation, depending on the seasonal change in spermatogenetic activity. (orig.)

  6. Synthesis, characterization, and first successful monkey imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) PET radiotracers.

    Science.gov (United States)

    Hamill, Terence G; Krause, Stephen; Ryan, Christine; Bonnefous, Celine; Govek, Steve; Seiders, T Jon; Cosford, Nicholas D P; Roppe, Jeffrey; Kamenecka, Ted; Patel, Shil; Gibson, Raymond E; Sanabria, Sandra; Riffel, Kerry; Eng, Waisi; King, Christopher; Yang, Xiaoqing; Green, Mitchell D; O'Malley, Stacey S; Hargreaves, Richard; Burns, H Donald

    2005-06-15

    Three metabotropic glutamate receptor subtype 5 (mGluR5) PET tracers have been labeled with either carbon-11 or fluorine-18 and their in vitro and in vivo behavior in rhesus monkey has been characterized. Each of these tracers share the common features of high affinity for mGluR5 (0.08-0.23 nM vs. rat mGluR5) and moderate lipophilicity (log P 2.8-3.4). Compound 1b was synthesized using a Suzuki or Stille coupling reaction with [11C]MeI. Compounds 2b and 3b were synthesized by a SNAr reaction using a 3-chlorobenzonitrile precursor. Autoradiographic studies in rhesus monkey brain slices using 2b and 3b showed specific binding in cortex, caudate, putamen, amygdala, hippocampus, most thalamic nuclei, and lower binding in the cerebellum. PET imaging studies in monkey showed that all three tracers readily enter the brain and provide an mGluR5-specific signal in all gray matter regions, including the cerebellum. The specific signal observed in the cerebellum was confirmed by the autoradiographic studies and saturation binding experiments that showed tracer binding in the cerebellum of rhesus monkeys. In vitro metabolism studies using the unlabeled compounds showed that 1a, 2a, and 3a are metabolized slower by human liver microsomes than by monkey liver microsomes. In vivo metabolism studies showed 3b to be long-lived in rhesus plasma with only one other more polar metabolite observed. (c) 2005 Wiley-Liss, Inc.

  7. Reference values of clinical chemistry and hematology parameters in rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Chen, Younan; Qin, Shengfang; Ding, Yang; Wei, Lingling; Zhang, Jie; Li, Hongxia; Bu, Hong; Lu, Yanrong; Cheng, Jingqiu

    2009-01-01

    Rhesus monkey models are valuable to the studies of human biology. Reference values for clinical chemistry and hematology parameters of rhesus monkeys are required for proper data interpretation. Whole blood was collected from 36 healthy Chinese rhesus monkeys (Macaca mulatta) of either sex, 3 to 5 yr old. Routine chemistry and hematology parameters, and some special coagulation parameters including thromboelastograph and activities of coagulation factors were tested. We presented here the baseline values of clinical chemistry and hematology parameters in normal Chinese rhesus monkeys. These data may provide valuable information for veterinarians and investigators using rhesus monkeys in experimental studies.

  8. Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda.

    Science.gov (United States)

    Lauck, Michael; Switzer, William M; Sibley, Samuel D; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Taylor, Bill; Shankar, Anupama; Ting, Nelson; Chapman, Colin A; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

    2013-10-21

    African non-human primates (NHPs) are natural hosts for simian immunodeficiency viruses (SIV), the zoonotic transmission of which led to the emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and evolution is limited by incomplete taxonomic and geographic sampling of NHPs, particularly in East Africa. In this study, we screened blood specimens from nine black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale National Park, Uganda, for novel SIVs using a combination of serology and "unbiased" deep-sequencing, a method that does not rely on genetic similarity to previously characterized viruses. We identified two novel and divergent SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in three and four animals, respectively, but with no animals co-infected. Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with SIVcol, previously discovered in black-and-white colobus from Cameroon. Although SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda, SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of functional motifs in the extracellular envelope glycoprotein (gp120) revealed that SIVkcol-2 is unique among primate lentiviruses in containing only 16 conserved cysteine residues instead of the usual 18 or more. Our results demonstrate that the genetic diversity of SIVs infecting black-and-white colobus across equatorial Africa is greater than previously appreciated and that divergent SIVs can co-circulate in the same colobine population. We also show that the use of "unbiased" deep sequencing for the detection of SIV has great advantages over traditional serological approaches, especially for studies of unknown or poorly characterized viruses. Finally, the detection of the first SIV containing only 16 conserved cysteines in the extracellular envelope protein

  9. Short parietal lobe connections of the human and monkey brain

    DEFF Research Database (Denmark)

    Catani, Marco; Robertsson, Naianna; Beyh, Ahmad

    2017-01-01

    projections were reconstructed for both species and results compared to identify similarities or differences in tract anatomy (i.e., trajectories and cortical projections). In addition, post-mortem dissections were performed in a human brain. The largest tract identified in both human and monkey brains...... and angular gyri of the inferior parietal lobule in humans but only to the supramarginal gyrus in the monkey brain. The third tract connects the postcentral gyrus to the anterior region of the superior parietal lobule and is more prominent in monkeys compared to humans. Finally, short U-shaped fibres...... and monkeys with some differences for those areas that have cytoarchitectonically distinct features in humans. The overall pattern of intraparietal connectivity supports the special role of the inferior parietal lobule in cognitive functions characteristic of humans....

  10. Macaque monkeys can learn token values from human models through vicarious reward.

    Science.gov (United States)

    Bevacqua, Sara; Cerasti, Erika; Falcone, Rossella; Cervelloni, Milena; Brunamonti, Emiliano; Ferraina, Stefano; Genovesio, Aldo

    2013-01-01

    Monkeys can learn the symbolic meaning of tokens, and exchange them to get a reward. Monkeys can also learn the symbolic value of a token by observing conspecifics but it is not clear if they can learn passively by observing other actors, e.g., humans. To answer this question, we tested two monkeys in a token exchange paradigm in three experiments. Monkeys learned token values through observation of human models exchanging them. We used, after a phase of object familiarization, different sets of tokens. One token of each set was rewarded with a bit of apple. Other tokens had zero value (neutral tokens). Each token was presented only in one set. During the observation phase, monkeys watched the human model exchange tokens and watched them consume rewards (vicarious rewards). In the test phase, the monkeys were asked to exchange one of the tokens for food reward. Sets of three tokens were used in the first experiment and sets of two tokens were used in the second and third experiments. The valuable token was presented with different probabilities in the observation phase during the first and second experiments in which the monkeys exchanged the valuable token more frequently than any of the neutral tokens. The third experiments examined the effect of unequal probabilities. Our results support the view that monkeys can learn from non-conspecific actors through vicarious reward, even a symbolic task like the token-exchange task.

  11. Dual-isotope single-photon emission computed tomography for dopamine and serotonin transporters in normal and parkinsonian monkey brains

    Energy Technology Data Exchange (ETDEWEB)

    Li, I-H. [Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan (China); Huang, W.-S. [Department of Nuclear Medicine, Tri-Service General Hospital, Taipei, 114, Taiwan (China); Yeh, C.-B. [Department of Psychiatry, Tri-Service General Hospital, Taipei, 114, Taiwan (China); Liao, M.-H.; Chen, C.-C.; Shen, L.-H. [Division of Isotope Application, Institute of Nuclear Energy Research, Taoyaun, 325 Taiwan (China); Liu, J.-C. [Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan (China); Ma, K.-H. [Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan (China)], E-mail: kuohsing91@yahoo.com.tw

    2009-08-15

    Introduction: Parkinson's disease (PD) affects both dopaminergic and serotonergic systems. In this study, we simultaneously evaluated dopamine and serotonin transporters in primates using dual-isotope single-photon emission computed tomography (SPECT) imaging and compared the results with traditional single-isotope imaging. Methods: Four healthy and one 6-OHDA-induced PD monkeys were used for this study. SPECT was performed over 4 h after individual or simultaneous injection of [{sup 99m}Tc]TRODAT-1 (a dopamine transporter imaging agent) and [{sup 123}I]ADAM (a serotonin transporter imaging agent). Results: The results showed that the image quality and uptake ratios in different brain regions were comparable between single- and dual-isotope studies. The striatal [{sup 99m}Tc]TRODAT-1 uptake in the PD monkey was markedly lower than that in normal monkeys. The uptake of [{sup 123}I]ADAM in the midbrain of the PD monkey was comparable to that in the normal monkeys, but there were decreased uptakes in the thalamus and striatum of the PD monkey. Conclusions: Our results suggest that dual-isotope SPECT using [{sup 99m}Tc]TRODAT-1 and [{sup 123}I]ADAM can simultaneously evaluate changes in dopaminergic and serotonergic systems in a PD model.

  12. Visual habit formation in monkeys with neurotoxic lesions of the ventrocaudal neostriatum

    Science.gov (United States)

    Fernandez-Ruiz, Juan; Wang, Jin; Aigner, Thomas G.; Mishkin, Mortimer

    2001-01-01

    Visual habit formation in monkeys, assessed by concurrent visual discrimination learning with 24-h intertrial intervals (ITI), was found earlier to be impaired by removal of the inferior temporal visual area (TE) but not by removal of either the medial temporal lobe or inferior prefrontal convexity, two of TE's major projection targets. To assess the role in this form of learning of another pair of structures to which TE projects, namely the rostral portion of the tail of the caudate nucleus and the overlying ventrocaudal putamen, we injected a neurotoxin into this neostriatal region of several monkeys and tested them on the 24-h ITI task as well as on a test of visual recognition memory. Compared with unoperated monkeys, the experimental animals were unaffected on the recognition test but showed an impairment on the 24-h ITI task that was highly correlated with the extent of their neostriatal damage. The findings suggest that TE and its projection areas in the ventrocaudal neostriatum form part of a circuit that selectively mediates visual habit formation. PMID:11274442

  13. Infection of human and non-human cells by a highly fusogenic primary CD4-independent HIV-1 isolate with a truncated envelope cytoplasmic tail

    International Nuclear Information System (INIS)

    Saha, Kunal; Yan Hui; Nelson, Julie A.E.; Zerhouni-Layachi, Bouchra

    2005-01-01

    Truncation of the envelope cytoplasmic tail has enabled FIV, SIV, and some laboratory HIV-1 strains to acquire broader cellular tropism and enhanced fusogenicity. Here we have characterized a primary CD4-independent HIV-1 isolate (92UG046-T8) with a truncated cytoplasmic tail that was able to infect and induce syncytia in primary lymphocytes from human, chimpanzee, and monkey, as well as CD4-negative cell lines from human and monkey. Increased syncytia were also noticeable with 293 cells expressing the cloned envelope from the 92UG046-T8 isolate suggesting envelope-mediated cellular fusion. Except pooled serum from HIV-1-infected individuals, monoclonal anti-envelope antibodies or antibodies/antagonists against CD4, CXCR4, and CCR5 were not able to prevent infection by the 92UG046-T8 isolate. This is the first report showing a primary HIV-1 variant with truncated cytoplasmic tail which is highly fusogenic and can infect a broad range of cells from human and non-human origins. In vivo evolution of similar HIV-1 mutants may have important implications in AIDS pathogenesis

  14. Distribution of neurotensin receptors in the primate hippocampal region: a quantitative autoradiographic study in the monkey and the postmortem human brain

    International Nuclear Information System (INIS)

    Kohler, Christer; Radesater, A.; Chan-Palay, V.

    1987-01-01

    The distribution of [ 3 H]neurotensin ([ 3 H]NT) binding sites in the monkey and the postmortem human brain was studied by using quantitative in vitro receptor autoradiography. Biochemical experiments carried out on tissue sections of the monkey hippocampus showed that the binding of [ 3 H]NT was saturable, reversible and of high specificity. The hippocampal [ 3 H]NT binding was displaced by fragment NT 8-13 but not fragment NT 1-8 of the peptide. The anatomical analysis showed a highly heterogeneous distribution of [ 3 H]NT binding sites within both the monkey and the human hippocampal region. In both species the highest density of [ 3 H]NT binding sites was found in the presubiculum (rank order of binding density: layer 2>6>1>3, 4, 5 in both monkey and man) and the entorhinal area (monkey: layer 4>6>5>1>2>3; human: layer 1=2>5>3). The subiculum and Ammon's horn were relatively poor in [ 3 H]NT binding sites in both species. In the area dentata the highest density of [ 3 H]NT binding sites was found in the hilar region. (author)

  15. Repair and mutagenesis of herpes simplex virus in UV-irradiated monkey cells

    International Nuclear Information System (INIS)

    Lytle, C.D.; Goddard, J.G.; Lin, C.H.

    1980-01-01

    Mutagenic repair in mammalian cells was investigated by determining the mutagenesis of UV-irradiated or unirradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cells. These results were compared with the results for UV-enhanced virus reactivation (UVER) in the same experimental situation. High and low multiplicities of infection were used to determine the effects of multiplicity reactivation (MR). UVER and MR were readily demonstrable and were approximately equal in amount in an infectious center assay. For this study, a forward-mutation assay was developed to detect virus mutants resistant to iododeoxycytidine (ICdR), probably an indication of the mutant virus being defective at its thymidine kinase locus. ICdR-resistant mutants did not have a growth advantage over wild-type virus in irradiated or unirradiated cells. Thus, higher fractions of mutant virus indicated greater mutagenesis during virus repair and/or replication. The data showed that: (1) unirradiated virus was mutated in unirradiated cells, providing a background level of mutagenesis; (2) unirradiated virus was mutated about 40% more in irradiated cells, indicating that virus replication (DNA synthesis) became more mutagenic as a result of cell irradiation; (3) irradiated virus was mutated much more (about 6-fold) than unirradiated virus, even in unirradiated cells; (4) cell irradiation did not change the mutagenesis of irradiated virus except at high multiplicity of infection. High multiplicity of infection did not demonstrate UVER or MR alone to be either error-free or error-prone. When the two processes were present simultaneously, they were mutagenic. (orig.)

  16. Marmoset monkeys evaluate third-party reciprocity.

    Science.gov (United States)

    Kawai, Nobuyuki; Yasue, Miyuki; Banno, Taku; Ichinohe, Noritaka

    2014-05-01

    Many non-human primates have been observed to reciprocate and to understand reciprocity in one-to-one social exchanges. A recent study demonstrated that capuchin monkeys are sensitive to both third-party reciprocity and violation of reciprocity; however, whether this sensitivity is a function of general intelligence, evidenced by their larger brain size relative to other primates, remains unclear. We hypothesized that highly pro-social primates, even with a relatively smaller brain, would be sensitive to others' reciprocity. Here, we show that common marmosets discriminated between human actors who reciprocated in social exchanges with others and those who did not. Monkeys accepted rewards less frequently from non-reciprocators than they did from reciprocators when the non-reciprocators had retained all food items, but they accepted rewards from both actors equally when they had observed reciprocal exchange between the actors. These results suggest that mechanisms to detect unfair reciprocity in third-party social exchanges do not require domain-general higher cognitive ability based on proportionally larger brains, but rather emerge from the cooperative and pro-social tendencies of species, and thereby suggest this ability evolved in multiple primate lineages. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  17. Perceptual Learning: 12-Month-Olds' Discrimination of Monkey Faces

    Science.gov (United States)

    Fair, Joseph; Flom, Ross; Jones, Jacob; Martin, Justin

    2012-01-01

    Six-month-olds reliably discriminate different monkey and human faces whereas 9-month-olds only discriminate different human faces. It is often falsely assumed that perceptual narrowing reflects a permanent change in perceptual abilities. In 3 experiments, ninety-six 12-month-olds' discrimination of unfamiliar monkey faces was examined. Following…

  18. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

    Directory of Open Access Journals (Sweden)

    Piotr Orlowski

    Full Text Available The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

  19. Monkey brain damage from radiation in the therapeutic range

    International Nuclear Information System (INIS)

    Nakagaki, H.; Brunhart, G.; Kemper, T.L.; Caveness, W.F.

    1976-01-01

    Twelve Macaca mulatta monkeys received 200 rads of supervoltage radiation to the whole brain per day, 5 days a week. The course in four monkeys was 4 weeks for a total dose of 4000 rads; in four monkeys, 6 weeks for 6000 rads; and in four monkeys, 8 weeks for 8000 rads. Four unirradiated monkeys served as controls. One from each group, sacrificed at 6 and 12 months from start of irradiation, is reported here. The results from 4000 rads were negligible; those from 8000 rads, profound, with gross brain destruction. The results from 6000 rads, within the therapeutic range, included at 6 months punctate necrotic lesions, 1 mm or less, widely scattered but with a predilection for the forebrain white matter. The reaction to these lesions ranged from an early macrophage response to calcification. Some were accompanied by focal edema. There were occasional examples of vascular endothelial proliferation. In addition, there were patches of dilated capillaries or telangiectasia. Twelve months after 6000 rads there were a few mineralized lesions and innumerable minute deposits of calcium and iron. A more active process was suggested by widely disseminated areas of telangiectasia, 6 to 12 mm in extent. The clinical course from this exposure included papilledema from the third to the sixth month and depressed visual evoked response accompanied by delta activity in the electroencephalogram from the sixth to the twelfth month

  20. 3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.

    Directory of Open Access Journals (Sweden)

    Manuel A Patarroyo

    Full Text Available T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2 and is known to bind to HLA-DRbeta1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vbeta12 and Vbeta6 TCR gene families in 67% of HLA-DRbeta1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRbeta1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

  1. A comparative analysis of global and local processing of hierarchical visual stimuli in young children (Homo sapiens) and monkeys (Cebus apella).

    Science.gov (United States)

    De Lillo, Carlo; Spinozzi, Giovanna; Truppa, Valentina; Naylor, Donna M

    2005-05-01

    Results obtained with preschool children (Homo sapiens) were compared with results previously obtained from capuchin monkeys (Cebus apella) in matching-to-sample tasks featuring hierarchical visual stimuli. In Experiment 1, monkeys, in contrast with children, showed an advantage in matching the stimuli on the basis of their local features. These results were replicated in a 2nd experiment in which control trials enabled the authors to rule out that children used spurious cues to solve the matching task. In a 3rd experiment featuring conditions in which the density of the stimuli was manipulated, monkeys' accuracy in the processing of the global shape of the stimuli was negatively affected by the separation of the local elements, whereas children's performance was robust across testing conditions. Children's response latencies revealed a global precedence in the 2nd and 3rd experiments. These results show differences in the processing of hierarchical stimuli by humans and monkeys that emerge early during childhood. 2005 APA, all rights reserved

  2. A. Femoralis in the small Green Monkey(Cercopithecus aethiops sabeus

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    Blagojević Miloš

    2016-01-01

    Full Text Available The small Green Monkey (Cercopithecus aethiops sabeus in large groups inhabits the African savannah. The animals delivered to us were from East Africa, that is from Kenya, Uganda and Tanzania. The length of the animal is 110 cm, and the tail itself is 50 cm long. They can often be seen in Zoos. According to data, mostly by zoo gardens, these monkeys live for about 15 to 17 years, exceptionally for 20 years. The objective of our work was to investigate a part of their cardiovascular system so in that way to contribute to a better knowledge of this animal body structure and accordingly to comparative anatomy in general. The investigation included 6 Small Green Monkeys, of both gender, 3-4 years old, body weight 2000-3000 grams, obtained from The Institute for Virusology, vaccines and serums from Belgrade. For obtaining the hindlimb arterial vascularization, after exsanguination of the animal, contrast mass of gelatin coloured with tempera was injected into the abdominal aorta. After injecting, the blood vessels were prepared and photographed. In the Small Green Monkey, femoral artery (A. femoralis is an continuation of the external iliac artery (A. iliaca externa. The branches of the femoral artery are: A. profunda femoris, A. saphena, A. genus descendens and A. caudalis femoralis. A. profunda femoris separates to A. circumflexa femoris lateralis, Ramus muscularis and A. circumflexa femoris medialis. In humans A. femoralis branches into: A. epigastrica superficialis, A. circumflexa ilium superficialis, Aa. pudendae externae, A. profunda femoris and A. genus descendens (A. descendens genus. A. profunda femoris branches into: A. circumflexa femoris lateralis, A. circumflexa femoris medialis and Aa. perforantes. In domestic animals, mammals, the branches of the femoral artery (A. femoralis are: A. circumflexa femoris lateralis, A. saphena, A. genus descendens and Aa. caudales femoris In the Small Green Monkey, humans and domestic mammals A. femoralis

  3. Present and potential distribution of Snub-nosed Monkey

    DEFF Research Database (Denmark)

    Nüchel, Jonas; Bøcher, Peder Klith; Svenning, Jens-Christian

    are the Snub-nosed Monkeys (Rhinopithecus), a temperate-subtropical East Asian genus. We use species distribution modeling to assess the following question of key relevancy for conservation management of Rhinopithecus; 1. Which climatic factors determine the present distribution of Rhinopithecus within...... distribution of Rhinopithecus within the region, considering climate, habitat availability and the locations of nature reserves. Keywords: biodiversity, biogeography, conservation, China, snub-nosed monkey, rhinopithecus, primates, species distribution modeling...

  4. Vascular origin of vildagliptin-induced skin effects in Cynomolgus monkeys: pathomechanistic role of peripheral sympathetic system and neuropeptide Y.

    Science.gov (United States)

    Hoffmann, Peter; Bentley, Phil; Sahota, Pritam; Schoenfeld, Heidi; Martin, Lori; Longo, Linda; Spaet, Robert; Moulin, Pierre; Pantano, Serafino; Dubost, Valerie; Lapadula, Dan; Burkey, Bryan; Kaushik, Virendar; Zhou, Wei; Hayes, Michael; Flavahan, Nick; Chibout, Salah-Dine; Busch, Steve

    2014-06-01

    The purpose of this article is to characterize skin lesions in cynomolgus monkeys following vildagliptin (dipeptidyl peptidase-4 inhibitor) treatment. Oral vildagliptin administration caused dose-dependent and reversible blister formation, peeling and flaking skin, erosions, ulcerations, scabs, and sores involving the extremities at ≥5 mg/kg/day and necrosis of the tail and the pinnae at ≥80 mg/kg/day after 3 weeks of treatment. At the affected sites, the media and the endothelium of dermal arterioles showed hypertrophy/hyperplasia. Skin lesion formation was prevented by elevating ambient temperature. Vildagliptin treatment also produced an increase in blood pressure and heart rate likely via increased sympathetic tone. Following treatment with vildagliptin at 80 mg/kg/day, the recovery time after lowering the temperature in the feet of monkeys and inducing cold stress was prolonged. Ex vivo investigations showed that small digital arteries from skin biopsies of vildagliptin-treated monkeys exhibited an increase in neuropeptide Y-induced vasoconstriction. This finding correlated with a specific increase in NPY and in NPY1 receptors observed in the skin of vildagliptin-treated monkeys. Present data provide evidence that skin effects in monkeys are of vascular origin and that the effects on the NPY system in combination with increased peripheral sympathetic tone play an important pathomechanistic role in the pathogenesis of cutaneous toxicity. © 2014 by The Author(s).

  5. A brain MRI atlas of the common squirrel monkey, Saimiri sciureus

    Science.gov (United States)

    Gao, Yurui; Schilling, Kurt G.; Khare, Shweta P.; Panda, Swetasudha; Choe, Ann S.; Stepniewska, Iwona; Li, Xia; Ding, Zhoahua; Anderson, Adam; Landman, Bennett A.

    2014-03-01

    The common squirrel monkey, Saimiri sciureus, is a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. It is one of the most commonly used South American primates in biomedical research. Unlike its Old World macaque cousins, no digital atlases have described the organization of the squirrel monkey brain. Here, we present a multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. In vivo MRI acquisitions include high resolution T2 structural imaging and low resolution diffusion tensor imaging. Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging. Cortical regions were manually annotated on the co-registered volumes based on published histological sections.

  6. Object permanence in orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri sciureus).

    Science.gov (United States)

    de Blois, S T; Novak, M A; Bond, M

    1998-06-01

    The authors tested orangutans (Pongo pygmaeus) and squirrel monkeys (Saimiri sciureus) on object permanence tasks. In Experiment 1, orangutans solved all visible displacements and most invisible displacements except those involving movements into 2 boxes successively. In Experiment 2, performance of orangutans on double invisible displacements and control displacements (assessing simple strategies) was compared. Orangutans did not use the simple strategy of selecting the box visited last by the experimenter. Instead, poorer performance on double invisible displacements may have been related to increased memory requirements. In Experiment 3, squirrel monkeys were tested using the procedure of Experiment 1. Squirrel monkeys solved visible but did not comprehend invisible displacements. Results suggest that orangutans but not squirrel monkeys possess Stage 6 object permanence capabilities.

  7. What interests them in the pictures?--differences in eye-tracking between rhesus monkeys and humans.

    Science.gov (United States)

    Hu, Ying-Zhou; Jiang, Hui-Hui; Liu, Ci-Rong; Wang, Jian-Hong; Yu, Cheng-Yang; Carlson, Synnöve; Yang, Shang-Chuan; Saarinen, Veli-Matti; Rizak, Joshua D; Tian, Xiao-Guang; Tan, Hen; Chen, Zhu-Yue; Ma, Yuan-Ye; Hu, Xin-Tian

    2013-10-01

    Studies estimating eye movements have demonstrated that non-human primates have fixation patterns similar to humans at the first sight of a picture. In the current study, three sets of pictures containing monkeys, humans or both were presented to rhesus monkeys and humans. The eye movements on these pictures by the two species were recorded using a Tobii eye-tracking system. We found that monkeys paid more attention to the head and body in pictures containing monkeys, whereas both monkeys and humans paid more attention to the head in pictures containing humans. The humans always concentrated on the eyes and head in all the pictures, indicating the social role of facial cues in society. Although humans paid more attention to the hands than monkeys, both monkeys and humans were interested in the hands and what was being done with them in the pictures. This may suggest the importance and necessity of hands for survival. Finally, monkeys scored lower in eye-tracking when fixating on the pictures, as if they were less interested in looking at the screen than humans. The locations of fixation in monkeys may provide insight into the role of eye movements in an evolutionary context.

  8. X-ray induced translocations in premeiotic germ cells of monkeys

    International Nuclear Information System (INIS)

    Buul, P.P.W. van

    1991-01-01

    Induction of reciprocal translocations by various X-ray exposures was studied in spermatogonial stem cells of rhesus monkeys (Macaca mulatta) and stump-tailed Macaques (arctoides) by means of spermatocyte analysis many cell generations after irradiation. The yields of trans-locations recovered from irradiated stump-tailed macaques were lower than those observed in rhesus monkeys and represent in fact the lowest induction rates per Gy ever recorded for experimental mammals. In the rhesus monkey a humped dose-effect relationship was found with 1.a homo -geneous response with (pseudo-)linear kinetics below 1 Gy, 2.much more variability at higher doses, and 3.no induction at all at doses of 4 Gy and above. It is suggested that the post-irradiation proliferation differentiation pattern of surviving rhesus monkey spermatogonial stem cells is mainly responsible for these characteristics of the dose-response curve. (author). 41 refs.; 1 fig.; 4 tabs

  9. Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humans.

    Science.gov (United States)

    Proksch, Joel W; Granvil, Camille P; Siou-Mermet, Raphaële; Comstock, Timothy L; Paterno, Michael R; Ward, Keith W

    2009-08-01

    Studies were conducted to evaluate the ocular penetration and systemic exposure to besifloxacin, a fluoroquinolone antibiotic, following topical ocular administration to animals and humans. Besifloxacin ophthalmic suspension (0.6%) was administered as a topical ocular instillation to pigmented rabbits, cynomolgus monkeys, and human subjects. At predetermined intervals after dosing, samples of ocular tissues and plasma were collected and analyzed for besifloxacin levels using HPLC/MS/MS methods. Besifloxacin demonstrated good ocular penetration in rabbits and monkeys, with rapid absorption and sustained concentrations observed in anterior ocular tissues through 24 h after a single administration. Maximum besifloxacin concentrations in conjunctiva, cornea, and aqueous humor of monkeys were 6.43 microg/g, 2.10 microg/g, and 0.796 microg/mL, respectively, after a single topical dose, and concentrations declined in these tissues with an apparent half-life of 5-14 h. Following a single topical ocular administration to humans, the maximum besifloxacin concentration in tears was 610 microg/g with concentrations decreasing to approximately 1.6 microg/g at 24 h. The resulting pharmacokinetic parameters for besifloxacin in human tears were evaluated relative to the MIC(90) values (microg/mL) for besifloxacin against Streptococcus pneumoniae (0.125), Staphylococcus aureus (0.25), Staphylococcus epidermidis (0.5), and Haemophilus influenzae (0.06). Following a single topical administration, the C(max)/MIC(90) ratios for besifloxacin in human tears were > or =1,220, and the AUC((0-24))/MIC(90) ratios were > or =2,500 for these relevant ocular pathogens. Following repeated 3-times daily (TID) topical ocular administration to human subjects with clinically diagnosed bacterial conjunctivitis, maximum besifloxacin concentrations in plasma were less than 0.5 ng/mL, on average. Taken together, the results of the current investigation provide a PK/PD-based rationale that supports the

  10. Preclinical deposition of pathological prion protein in muscle of experimentally infected primates.

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    Susanne Krasemann

    Full Text Available Prion diseases are transmissible fatal neurodegenerative disorders affecting humans and animals. A central step in disease progression is the accumulation of a misfolded form (PrP(Sc of the host encoded prion protein (PrP(C in neuronal and non-neuronal tissues. The involvement of peripheral tissues in preclinical states increases the risk of accidental transmission. On the other hand, detection of PrP(Sc in non-neuronal easy-accessible compartments such as muscle may offer a novel diagnostic tool. Primate models have proven invaluable to investigate prion diseases. We have studied the deposition of PrP(Sc in muscle and central nervous system of rhesus monkeys challenged with sporadic Creutzfeldt-Jakob disease (sCJD, variant CJD (vCJD and bovine spongiform encephalopathy (BSE in preclinical and clinical stage using biochemical and morphological methods. Here, we show the preclinical presence of PrP(Sc in muscle and central nervous system of rhesus monkeys experimentally infected with vCJD.

  11. Geophagy in brown spider monkeys (Ateles hybridus) in a lowland tropical rainforest in Colombia.

    Science.gov (United States)

    Link, Andres; de Luna, Ana Gabriela; Arango, Ricardo; Diaz, Maria Clara

    2011-01-01

    Spider monkeys and howler monkeys are the only Neotropical primates that eat soil from mineral licks. Not all species within these genera visit mineral licks, and geophagy has been restricted to populations of Ateles belzebuth belzebuth,Ateles belzebuth chamek and Alouatta seniculus in western Amazonian rainforests. With the aid of a camera trap we studied the visitation patterns of a group of brown spider monkeys (Ateles hybridus) to a mineral lick at Serrania de Las Quinchas, in Colombia. Spider monkeys visited the lick frequently throughout the year, with a monthly average of 21.7 ± 7.2 visits per 100 days of camera trapping (n = 14 months). Spider monkeys visited the mineral lick almost always on days with no rain, or very little (<3 mm) rain, suggesting that proximate environmental variables might determine spider monkeys' decisions to come to the ground at the licks. This study expands the geographical occurrence of mineral lick use by spider monkeys providing additional data for future assessments on the biogeographical correlates of mineral lick use by platyrrhines. Copyright © 2011 S. Karger AG, Basel.

  12. An enzootic outbreak of acute disease associated with pathogenic E. coli in Adler monkey colony.

    Science.gov (United States)

    Lapin, Boris A; Yakovleva, Lelita A; Dzhikidze, Eteri K; Gvozdik, Tatiana E; Agumava, Aslan A; Stasilevich, Zinaida K; Danilova, Irina G

    2015-12-01

    In spring 2009 in Adler colony of the Institute of Medical Primatology, a large enzootic outbreak of acute intestine infection associated with pathogenic E. coli occurred and caused 5% mortality of population (209 animals). The epidemiological analysis, bacteriological investigation, postmortem examination, histological analysis, and PCR were used to identify the infectious agent. Marked hemorrhagic diathesis, lethargy, dehydration, diarrhea with blood, wasting, and sometimes dystrophic changes in articular cartilages were noted. Morphologically, hemorrhagic enterocolitis and massive hemorrhages were found. PCR investigation of bacteriologically isolated E. coli characterized it as enteropathogenic and enteroinvasive E. coli. The outbreak in Adler colony slightly differed from similar outbreak in Florida in 2014 by more marked hemorrhagic diathesis and articular changes in some monkeys caused by polyavitaminosis developed in the course of infection. Sensitive to infection were M. mulatta, M. fascicularis, Cercopithecus aethiops, P. hamadryas and anubis, and Cebus capucinus. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

    Directory of Open Access Journals (Sweden)

    Chenggu Cai

    Full Text Available Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2 and Tas1r3 (taste receptor type 1 member 3. Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

  14. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

    Science.gov (United States)

    Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

    2016-01-01

    Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

  15. Movement disorders induced in monkeys by chronic haloperidol treatment

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B; Santelli, S; Lusink, G

    1977-01-01

    After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1 to 6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.

  16. Placental Transport of Zidovudine in the Rhesus Monkey

    Science.gov (United States)

    King, Thomas S.; Henderson, George I.; Schenker, Steven; Schenken, Robert S.

    1993-01-01

    Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37±15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal rafio ranged from 0.08 ± 0.11 at 20 min to 4.2 ± 4.2 at 180 min post-injection. Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment. PMID:18475334

  17. Distribution of [1-14C]acrylonitrile in rat and monkey

    International Nuclear Information System (INIS)

    Sandberg, E.Ch.; Slanina, P.

    1980-01-01

    The distribution of [1- 14 C]acrylonitrile (ACN) in rat and monkey has been studied by whole-body autoradiography, after being administered orally and intravenously to rats and orally to monkeys. Uptake of radioactivity was seen in the blood, liver, kidney, lung, adrenal cortex and stomach mucosa. (Auth.)

  18. IDENTIFICATION OF MYCOBACTERIUM GENAVENSE IN A DIANA MONKEY (CERCOPITHECUS DIANA) BY POLYMERASE CHAIN REACTION AND HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY.

    Science.gov (United States)

    Kelly, Kathleen M; Wack, Allison N; Bradway, Dan; Simons, Brian W; Bronson, Ellen; Osterhout, Gerard; Parrish, Nicole M; Montali, Richard J

    2015-06-01

    A 25-yr-old Diana monkey (Cercopithecus diana) with a 1.5-yr history of chronic colitis and diarrhea was found to have disseminated granulomatous disease with intralesional acid fast bacilli. Bacilli were identified as Mycobacterium genavense by polymerase chain reaction, sequencing of the 16S-23S ribosomal RNA intergenic spacer (ITS) gene, and mycolic acid analysis by high-performance liquid chromatography. Mycobacterium genavense is a common cause of mycobacteriosis in free-ranging and captive birds. In addition, recognition of opportunistic infection in human immunodeficiency virus-positive patients is increasing. Disease manifestations of M. genavense are similar to Mycobacterium avium complex (MAC) and include fever, wasting, and diarrhea with disseminated disease. Similar clinical signs and lesions were observed in this monkey. Mycobacterium genavense should be considered as a differential for disseminated mycobacterial disease in nonhuman primates as this agent can mimic MAC and related mycobacteria.

  19. A Comparative Study of Growth Patterns in Crested Langurs and Vervet Monkeys

    Directory of Open Access Journals (Sweden)

    Debra R. Bolter

    2011-01-01

    Full Text Available The physical growth patterns of crested langurs and vervet monkeys are investigated for several unilinear dimensions. Long bone lengths, trunk height, foot length, epiphyseal fusion of the long bones and the pelvis, and cranial capacity are compared through six dental growth stages in male Trachypithecus cristatus (crested langurs and Cercopithecus aethiops (vervet monkeys. Results show that the body elements of crested langurs mature differently than those of vervets. In some dimensions, langurs and vervets grow comparably, in others vervets attain adult values in advance of crested langurs, and in one feature the langurs are accelerated. Several factors may explain this difference, including phylogeny, diet, ecology, and locomotion. This study proposes that locomotor requirements affect differences in somatic growth between the species.

  20. Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

    Science.gov (United States)

    Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

    2013-01-01

    Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

  1. SV40 host-substituted variants: a new look at the monkey DNA inserts and recombinant junctions.

    Science.gov (United States)

    Singer, Maxine; Winocour, Ernest

    2011-04-10

    The available monkey genomic data banks were examined in order to determine the chromosomal locations of the host DNA inserts in 8 host-substituted SV40 variant DNAs. Five of the 8 variants contained more than one linked monkey DNA insert per tandem repeat unit and in all cases but one, the 19 monkey DNA inserts in the 8 variants mapped to different locations in the monkey genome. The 50 parental DNAs (32 monkey and 18 SV40 DNA segments) which spanned the crossover and flanking regions that participated in monkey/monkey and monkey/SV40 recombinations were characterized by substantial levels of microhomology of up to 8 nucleotides in length; the parental DNAs also exhibited direct and inverted repeats at or adjacent to the crossover sequences. We discuss how the host-substituted SV40 variants arose and the nature of the recombination mechanisms involved. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Frequency of Toxoplasma gondii antibodies in tufted capuchin monkeys (Cebus apella nigritus from an ecological station in the State of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Rodrigo Costa da Silva

    2013-02-01

    Full Text Available Toxoplasmosis is a worldwide zoonosis caused by Toxoplasma gondii, an obligate intracellular parasite protozoan. A large percentage of animals presents specific antibodies caused by a previous exposition, resulting in a chronic infection. Felides are the definitive hosts and the other warm-blooded animals, including primates, are the intermediate hosts. This study was aimed to determine the prevalence of T. gondii infection in free-living tufted capuchin monkeys (Cebus apella nigritus from an ecological station located on Mata de Santa Teresa, Ribeirão Preto, SP, Brazil. T. gondii antibodies were analyzed by modified agglutination test (MAT in serum samples of 36 tufted capuchin monkeys, considering eight as cut-off titer. From the studied animals, 3/36 (8.33%; CI95% 3.0-21.9% presented T. gondii antibodies, all with titer 32. No significative difference was observed relating to the sex (1/3 male and 2/3 female, and to the age (1/3 young and 2/3 adult (P>0.05. Thus, these results demonstrate the presence of T. gondii antibodies in primates from São Paulo state.

  3. Reduction on OFF-responses of Electroretinogram in Monkeys with Long-term High Intraocular Pressure

    Directory of Open Access Journals (Sweden)

    Ke-Gao Liu

    2017-01-01

    Conclusions: Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction of photoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy.

  4. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  5. Proximal and Distal Predictors of the Spider Monkey's Stress Levels in Fragmented Landscapes.

    Directory of Open Access Journals (Sweden)

    José D Ordóñez-Gómez

    Full Text Available The rapid loss, fragmentation and degradation of tropical forests threaten the survival of many animal species. However, the way in which these phenomena affect animal health has been poorly explored, thus limiting the design of appropriate conservation strategies. To address this, here we identified using linear mixed models the effect of proximal (diet, activity pattern, hunting and logging and distal (sum of the basal areas of fruiting-tree species [SBAFS], landscape forest cover and degree of forest fragmentation variables over fecal glucocorticoid metabolite (fGCM levels-hormones associated with animal health and fitness-of six groups of spider monkeys (Ateles geoffroyi inhabiting six landscapes with different spatial structures in Mexico. Proximal variables showed a stronger predictive power over fGCMs than distal. In this sense, increases in travel time, the occurrence of hunting, and reductions in rest time and fruit consumption resulted in higher fGCM levels. Regarding distal variables, increases in SBAFS were negatively related to fGCM levels, thus suggesting that food scarcity increases stress hormone levels. Nevertheless, contrary to theoretical expectations, spider monkeys living in smaller tracts of forest spent less time travelling, but the same time feeding on fruit as those in more forested areas. The lower net energy return associated with this combination of factors would explain why, contrary to theoretical expectations, increased forest cover was associated with increased levels of fGCMs in these groups. Our study shows that, at least in the short term, spider monkeys in fragmented landscapes do not always present higher levels of stress hormones compared to those inhabiting continuous forest, and the importance of preserving fruit sources and controlling hunting for reducing the levels of stress hormones in free ranging spider monkeys.

  6. Exploring decoy effects on computerized task preferences in rhesus monkeys (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Audrey E. Parrish

    2018-05-01

    Full Text Available The asymmetric dominance effect or decoy effect emerges when a third inferior option is introduced to a choice set. The decoy option, although typically not chosen, impacts relative preference for the original two options. This decisional bias stands in contrast with rational choice theory, which dictates that choice behavior should remain consistent for the original options with the addition of different alternatives to a choice set such as the decoy. In the current study, we assessed the decoy effect in rhesus monkeys using a computerized task battery that introduced two different computerized tasks, including a matching-to-sample task and a psychomotor task called PURSUIT. Decoy tasks were designed such that they were inferior versions of these original task options, requiring longer time to completion (via slowed cursor speeds and subsequently reduced reinforcement rates. Monkeys learned to associate unique icons for each task (including for decoy tasks, and used these icons to select their preferred task from a choice set of two to three task options. Monkeys learned to perform all tasks, but did not show evidence of the decoy effect using this task preference paradigm. We discuss the role of initial task preference (and task biases, task type (symbolic vs. perceptual, and decoy effect sizes in light of these findings. We contrast the current results to previous findings of the decoy effect in rhesus monkeys using a perceptual paradigm as well as to other evidence of the decoy effect in non-primate animal species.

  7. Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors.

    Science.gov (United States)

    Abbink, Peter; Maxfield, Lori F; Ng'ang'a, David; Borducchi, Erica N; Iampietro, M Justin; Bricault, Christine A; Teigler, Jeffrey E; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A; Zhao, Guoyan; Virgin, Herbert W; Korber, Bette; Barouch, Dan H

    2015-02-01

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

    Science.gov (United States)

    Yuan, Meng-Ke; Tao, Yong; Yu, Wen-Zhen; Kai, Wang; Jiang, Yan-Rong

    2010-08-25

    To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

  9. The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, M B; Fuxe, K; Werge, T

    2002-01-01

    and lack of EPS in rodents could also be observed in non-human primates. We investigated the effects of CGS 21680 on behaviours induced by D-amphetamine and (-)-apomorphine in EPS-sensitized Cebus apella monkeys. CGS 21680 was administered s.c. in doses of 0.01, 0.025 and 0.05 mg/kg, alone...... and in combination with D-amphetamine and (-)-apomorphine. The monkeys were videotaped after drug administration and the tapes were rated for EPS and psychosis-like symptoms. CGS 21680 decreased apomorphine-induced behavioural unrest, arousal (0.01-0.05 mg/kg) and stereotypies (0.05 mg/kg) while amphetamine...... showed a functional anti-dopaminergic effect in Cebus apella monkeys without production of EPS. This further substantiates that adenosine A2A receptor agonists may have potential as antipsychotics with atypical profiles....

  10. Human-Rhesus Monkey conflict at Rampur Village under Monohardi Upazila in Narsingdi District of Bangladesh

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    M.F. Ahsan

    2014-06-01

    Full Text Available Human-Rhesus monkey conflicts were recorded at Rampur Village under Khidirpur Union Parishad of Monohardi upazila under Narsingdi District in Bangladesh from April to September 2012. There were three groups of Rhesus monkeys living in the area. The focal study group comprised 26 individuals (4 adult males, 6 adult females, 10 juveniles and 6 infants. The monkeys consumed parts of 10 plant species. From the questionnaire survey, it was found that the greatest damage caused by monkeys was on betel leaf vines and the least damage on vegetables. Eighty percent respondents opted to conserve the monkeys and 20% opined status quo. Some restricted areas (especially khas lands may be identified and planted with some fruit trees for survival of monkeys and for reducing conflicts with humans.

  11. Comparison of the chromosomal radiosensitivity of blood lymphocytes and stem-cell spermatogonia in the rhesus monkey and the mouse

    International Nuclear Information System (INIS)

    Buul, P.P.W. van; Richardson, J.F.; Boer, P. de; Zwanenburg, S.

    1980-01-01

    By experiments similar to those with the mouse we studied, in the rhesus monkey (Macaca mulatta), the induction by X-rays of reciprocal translocations in steam-cell spermatogonia and of dicentric chromosomes in blood lymphocytes. Human blood lymphocytes and rhesus monkey lymphocytes showed about equal sensitivity to dicentric induction. This equal radiosensitivity of somatic cells, however, provides no clue to the quantitative extrapolation to the human situation of the data obtained on translocation induction in stem-cell spermatogonia of the rhesus monkey. In our opinion, only direct observations on induced chromosomal aberrations in germ cells of higher primates and man can play a decisive role in estimating human genetic radiation risks arising from chromosomal aberrations. (orig./AJ)

  12. Histological and histomorphometrical evaluation of tissue reactions adjacent to endosteal implants in monkeys

    DEFF Research Database (Denmark)

    Gotfredsen, K; Rostrup, E; Hjörting-Hansen, E

    1992-01-01

    A qualitative and quantitative histological study of the initial healing response adjacent to 24 submerged and non-submerged implants placed in the lower jaws of 6 monkeys is presented. The histomorphometric analysis showed no significant differences in mineralized bone-implant contact length...

  13. Fluoxetine Administration in Juvenile Monkeys: Implications for Pharmacotherapy in Children

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    Mari S. Golub

    2018-02-01

    Full Text Available Fluoxetine therapy has been approved for children with major depressive disorder and obsessive compulsive disorder for over 14 years and has expanded to other childhood behavior disorders. As use increases, more detail on fluoxetine effects during juvenile brain development can help maintain safe and effective use of this therapy. Here, a narrative review is provided of previously published findings from a large nonhuman primate project. Fluoxetine was administered to juvenile male rhesus monkeys for an extended period (2 years prior to puberty. Compared to controls, treated monkeys showed sleep disruption, facilitated social interaction, greater impulsivity, and impaired sustained attention during treatment. No effects on growth were seen. Metabolomics assays characterized a distinctive response to fluoxetine and demonstrated individual differences that were related to the impulsivity measure. Fluoxetine interactions with monoamine oxidase A polymorphisms that influenced behavior and metabolomics markers were an important, previously unrecognized finding of our studies. After treatment was discontinued, some behavioral effects persisted, but short-term memory and cognitive flexibility testing did not show drug effects. This detailed experimental work can contribute to clinical research and continued safe and effective fluoxetine pharmacotherapy in children.

  14. 77 FR 13612 - Anti-Infective Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-03-07

    ... plague (plague infection with extensive lung involvement) in African Green Monkeys and provide advice.... Safety and other supportive information is derived from clinical studies and post-marketing experience in... studies and post-marketing experience in humans. FDA intends to make background material available to the...

  15. Monkeying around: Use of Survey Monkey as a Tool for School Social Work

    Science.gov (United States)

    Massat, Carol Rippey; McKay, Cassandra; Moses, Helene

    2009-01-01

    This article describes the use of an online survey tool called Survey Monkey, which can be used by school social workers and school social work educators for evaluation of practice, needs assessment, and program evaluation. Examples of questions are given. Principles of writing good survey questions are described. (Contains 2 tables and 1…

  16. Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

    International Nuclear Information System (INIS)

    Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

    1981-01-01

    Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats

  17. Gastric acid secretion response in the Cebus apella: a monkey model of chronic Chagas disease Respuesta secretora acida gastrica en el Cebus apella, un modelo animal de la enfermedad de Chagas cronica

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Falasca

    1992-12-01

    Full Text Available The objective was to study the secretory pattern, both basal and stimulated either by histamine (0.1 mg/kg or pentagastrin (64 ug/kg in eighteen Cebus apella monkeys chronically infected with different T. cruzi strains (CA1, n=10; Colombian, n=4 and Tulahuen, n=4 and to describe the morphological findings in the gastrointestinal tract in twelve infected (6 sacrificed and 6 spontaneously dead and four healthy monkeys. All infected monkeys and 35 healthy ones were evaluated by contrast X-ray examination. No differences were observed in basal acid output between control and infected groups. Animals infected with the Tulahuen and Colombian strains showed significant lower values of peak acid output in response to histamine or pentagastrin (pEl objetivo fue estudiar la respuesta secretora basal y estimulada por histamina (0.1 mg/kg o pentagastrina (64 ug/kg en 18 monos Cebus apella cronicamente infectados con diferentes cepas de T. cruzi (CA1 n=10; Colombiana n=4 y Tulahuén n=4. Además se describieron los hallazgos morfológicos en el tracto gastrointestinal de 12 animales muertos (6 sacrificados y 6 espontaneamente. Se evaluó radiológicamente el tracto gastrointestinal de 35 Cebus sp. sanos (controles y 18 infectados crónicamente. Se estudiaron histopatologicamente 4 controles y 12 infectados. No hubo diferencias en la secreción basal ácida entre los grupos control e infectado. Los animales infectados con la cepa Tulahuén y Colombian tuvieron valores más bajos en el pico de secreción ácida, como respuesta a la histamina o a la pentagastrina (p<0.01 y p<0.05 respectivamente; test "t" con respecto a los controles. Los estudios con contraste de bario mostraron agrandamiento y dilatación del colon en 3 animales infectados. En las autopsias de los chagásicos se encontraron lesiones histologicas en el 75% de los casos (solo en colon, 33%; en colon y esofago, 42%. En el grupo CA1, la secreción ácida estuvo dentro de los parámetros normales

  18. Suppression of metabolic activity caused by infantile strabismus and strabismic amblyopia in striate visual cortex of macaque monkeys.

    Science.gov (United States)

    Wong, Agnes M F; Burkhalter, Andreas; Tychsen, Lawrence

    2005-02-01

    Suppression is a major sensorial abnormality in humans and monkeys with infantile strabismus. We previously reported evidence of metabolic suppression in the visual cortex of strabismic macaques, using the mitochondrial enzyme cytochrome oxidase as an anatomic label. The purpose of this study was to further elucidate alterations in cortical metabolic activity, with or without amblyopia. Six macaque monkeys were used in the experiments (four strabismic and two control). Three of the strabismic monkeys had naturally occurring, infantile strabismus (two esotropic, one exotropic). The fourth strabismic monkey had infantile microesotropia induced by alternating monocular occlusion in the first months of life. Ocular motor behaviors and visual acuity were tested after infancy in each animal, and development of stereopsis was recorded during infancy in one strabismic and one control monkey. Ocular dominance columns (ODCs) of the striate visual cortex (area V1) were labeled using cytochrome oxidase (CO) histochemistry alone, or CO in conjunction with an anterograde tracer ([H 3 ]proline or WGA-HRP) injected into one eye. Each of the strabismic monkeys showed inequalities of metabolic activity in ODCs of opposite ocularity, visible as rows of lighter CO staining, corresponding to ODCs of lower metabolic activity, alternating with rows of darker CO staining, corresponding to ODCs of higher metabolic activity. In monkeys who had infantile strabismus and unilateral amblyopia, lower metabolic activity was found in (suppressed) ODCs driven by the nondominant eye in each hemisphere. In monkeys who had infantile esotropia and alternating fixation (no amblyopia), metabolic activity was lower in ODCs driven by the ipsilateral eye in each hemisphere. The suppression included a monocular core zone at the center of ODCs and binocular border zones at the boundaries of ODCs. This suppression was not evident in the monocular lamina of the LGN, indicating an intracortical rather than

  19. T-cell tropism of simian T-cell leukaemia virus type 1 and cytokine profiles in relation to proviral load and immunological changes during chronic infection of naturally infected mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Souquière, Sandrine; Mouinga-Ondeme, Augustin; Makuwa, Maria; Beggio, Paola; Radaelli, Antonia; De Giuli Morghen, Carlo; Mortreux, Franck; Kazanji, Mirdad

    2009-08-01

    Although a wide variety of non-human primates are susceptible to simian T-cell leukaemia virus type 1 (STLV-1), little is known about the virological or molecular determinants of natural STLV-1 infection. We determined STLV-1 virus tropism in vivo and its relation to the immune response by evaluating cytokine production and T-cell subsets in naturally infected and uninfected mandrills. With real-time PCR methods, we found that STLV-1 in mandrills infects both CD4(+) and CD8(+) T cells; however, proviral loads were significantly higher (P = 0.01) in CD4(+) than in CD8(+) cells (mean STLV-1 copies number per 100 cells (+/- SD) was 7.8 +/- 8 in CD4(+) T cells and 3.9 +/- 4.5 in CD8(+) T cells). After culture, STLV-1 provirus was detected in enriched CD4(+) but not in enriched CD8(+) T cells. After 6 months of culture, STLV-1-transformed cell lines expressing CD3(+), CD4(+) and HLADR(+) were established, and STLV-1 proteins and tax/rex mRNA were detected. In STLV-1 infected monkeys, there was a correlation between high proviral load and elevated levels of interleukin (IL)-2, IL-6, IL-10, interferon-gamma and tumour necrosis factor-alpha. The two monkeys with the highest STLV-1 proviral load had activated CD4(+)HLADR(+) and CD8(+)HLADR(+) T-cell subsets and a high percentage of CD25(+) in CD4(+) and CD8(+) T cells. Our study provides the first cellular, immunological and virological characterization of natural STLV-1 infection in mandrills and shows that they are an appropriate animal model for further physiopathological studies of the natural history of human T-cell leukaemia viruses.

  20. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    Directory of Open Access Journals (Sweden)

    Osterhaus Albert DME

    2004-11-01

    Full Text Available Abstract A pol-fragment of simian immunodeficiency virus (SIV that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus was detected in two mandrills (Mandrillus sphinx from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdrl-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdrl.

  1. Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

    Science.gov (United States)

    Ikeda, Yasuhiro; Nishiguchi, Koji M; Miya, Fuyuki; Shimozawa, Nobuhiro; Funatsu, Jun; Nakatake, Shunji; Fujiwara, Kohta; Tachibana, Takashi; Murakami, Yusuke; Hisatomi, Toshio; Yoshida, Shigeo; Yasutomi, Yasuhiro; Tsunoda, Tatsuhiko; Nakazawa, Toru; Ishibashi, Tatsuro; Sonoda, Koh-Hei

    2018-02-01

    To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis. Retinal degeneration with cystoid macular edema was observed in both eyes of one 14-year-old female monkey. In her examinations, the full-field ERGs were nonrecordable and the outer layer of the retina in the parafoveal area was not visible on OCT imaging. Moreover, less frequent pigmentary retinal anomalies also were observed in her 3-year-old nephew. His full-field ERGs were almost nonrecordable and the outer layer was not visible in the peripheral retina. His father was her cousin (the son of her mother's older brother) and his mother was her younger half-sibling sister with a different father. The hereditary nature is highly probable (autosomal recessive inheritance suspected). However, whole-exome analysis performed identified no pathogenic mutations in these monkeys.

  2. Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.

    Directory of Open Access Journals (Sweden)

    Kriti Tyagi

    Full Text Available The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites.Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively.Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1 showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3 showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs for human erythrocyte receptors. However, the third protein (PkTRAg67.1 utilized the additional but different human erythrocyte receptor(s as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite.Recognition and sharing of human erythrocyte receptor(s by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host.

  3. Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.

    Science.gov (United States)

    Tyagi, Kriti; Gupta, Deepali; Saini, Ekta; Choudhary, Shilpa; Jamwal, Abhishek; Alam, Mohd Shoeb; Zeeshan, Mohammad; Tyagi, Rupesh K; Sharma, Yagya D

    2015-01-01

    The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs) to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites. Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively. Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1) showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3) showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs) for human erythrocyte receptors. However, the third protein (PkTRAg67.1) utilized the additional but different human erythrocyte receptor(s) as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite. Recognition and sharing of human erythrocyte receptor(s) by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host.

  4. Neural Monkey: An Open-source Tool for Sequence Learning

    Directory of Open Access Journals (Sweden)

    Helcl Jindřich

    2017-04-01

    Full Text Available In this paper, we announce the development of Neural Monkey – an open-source neural machine translation (NMT and general sequence-to-sequence learning system built over the TensorFlow machine learning library. The system provides a high-level API tailored for fast prototyping of complex architectures with multiple sequence encoders and decoders. Models’ overall architecture is specified in easy-to-read configuration files. The long-term goal of the Neural Monkey project is to create and maintain a growing collection of implementations of recently proposed components or methods, and therefore it is designed to be easily extensible. Trained models can be deployed either for batch data processing or as a web service. In the presented paper, we describe the design of the system and introduce the reader to running experiments using Neural Monkey.

  5. Metabolism and disposition of ABT-894, a novel α4β2 neuronal acetylcholine receptor agonist, in mice and monkeys.

    Science.gov (United States)

    Liu, Hong; Fu, Wentao; Wetter, Jill; Xu, Hongyu; Guan, Zhiwen; Stuart, Patricia

    2014-06-01

    1.  Metabolism and disposition of ABT-894 was investigated in hepatocytes, in mice and monkeys receiving [(14)C]ABT-894. 2.  In hepatocytes, turnover rate of ABT-894 was slow in all species with more than 90% of parent remaining. M3 (carbamoyl glucuronide) and M6 (mono-oxidation) were detected across species. 3.  ABT-894 showed species-specific disposition profiles. ABT-894 was primarily eliminated by renal secretion in mice. Whereas, monkey mainly cleared ABT-894 metabolically. 4.  ABT-894 underwent two primary routes of metabolism in monkeys: N-carbamoyl glucuronidation to form M3 and oxidation product M1. M3 was the major metabolite in monkey excreta. M3 was observed in mice urine. Circulating levels of M3 in terms of M3/ABT-894 ratios were essentially absent in mice, but were high in monkeys. 5.  Understanding the species difference in the clearance mechanism is the key to the accurate projection of the human clearance and preclinical safety assessment. Lack of species difference in the metabolism of ABT-894 in hepatocytes certainly creates a challenge in predicting its metabolism and pharmacokinetics in human. Based on available metabolism and pharmacokinetic data of ABT-894 in human, monkey is the preferred species in predicting human clearance since it presents a similar clearance mechanism from that observed in human.

  6. 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.

  7. Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation.

    Directory of Open Access Journals (Sweden)

    Francis Fieni

    Full Text Available HIV is shed in semen but the anatomic site of virus entry into the genital secretions is unknown. We determined viral RNA (vRNA levels and the envelope gene sequence in the SIVmac 251 viral populations in the genital tract and semen of 5 adult male rhesus monkeys (Macaca mulatta that were infected after experimental penile SIV infection. Paired blood and semen samples were collected from 1-9 weeks after infection and the monkeys were necropsied eleven weeks after infection. The axillary lymph nodes, testes, epididymis, prostate, and seminal vesicles were collected and vRNA levels and single-genome analysis of the SIVmac251 env variants was performed. At the time of semen collection, blood vRNA levels were between 3.09 and 7.85 log10 vRNA copies/ml plasma. SIV RNA was found in the axillary lymph nodes of all five monkeys and in 3 of 5 monkeys, all tissues examined were vRNA positive. In these 3 monkeys, vRNA levels (log10 SIVgag copies/ug of total tissue RNA in the axillary lymph node (6.48 ± 0.50 were significantly higher than in the genital tract tissues: testis (3.67 ± 2.16; p<0.05, epididymis (3.08 ± 1.19; p<0.0001, prostate (3.36 ± 1.30; p<0.01, and seminal vesicle (2.67 ± 1.50; p<0.0001. Comparison of the SIVmac251 env viral populations in blood plasma, systemic lymph node, and genital tract tissues was performed in two of the macaques. Visual inspection of the Neighbor-Joining phylograms revealed that in both animals, all the sequences were generally distributed evenly among all tissue compartments. Importantly, viral populations in the genital tissues were not distinct from those in the systemic tissues. Our findings demonstrate striking similarity in the viral populations in the blood and male genital tract tissues within 3 months of penile SIV transmission.

  8. Effect of target animacy on hand preference in Sichuan snub-nosed monkeys (Rhinopithecus roxellana).

    Science.gov (United States)

    Zhao, Dapeng; Tian, Xiangling; Liu, Xinchen; Chen, Zhuoyue; Li, Baoguo

    2016-09-01

    Twenty-eight captive Sichuan snub-nosed monkeys (Rhinopithecus roxellana) were involved in the current study. Many individuals showed handedness, with a modest tendency toward left-hand use especially for animate targets, although no group-level handedness was found. There was no significant gender difference in the direction and strength of hand preference for both targets. Females showed a significantly higher overall rate of actions toward animate targets than inanimate targets for both hands, whereas males displayed almost the reversed pattern. There were no significant interactions between lateral hand use and target animacy for either males or females. Most individuals showed rightward or leftward laterality shift trends between inanimate and animate targets. These findings to some extent support the existence of a potential trend concerning a categorical neural distinction between targets demanding functional manipulation (inanimate objects) and those demanding social manipulation (animate objects), even though specialized hand preference based on target animacy has not been fully established in this arboreal Old World monkey species.

  9. Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

    Science.gov (United States)

    Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

    2012-12-15

    Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

    Science.gov (United States)

    de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

    2018-05-02

    This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

  11. Early monocular defocus disrupts the normal development of receptive-field structure in V2 neurons of macaque monkeys.

    Science.gov (United States)

    Tao, Xiaofeng; Zhang, Bin; Shen, Guofu; Wensveen, Janice; Smith, Earl L; Nishimoto, Shinji; Ohzawa, Izumi; Chino, Yuzo M

    2014-10-08

    Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion. Copyright © 2014 the authors 0270-6474/14/3413840-15$15.00/0.

  12. Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection

    KAUST Repository

    LaMonte, Gregory; Orjuela-Sanchez, Pamela; Wang, Lawrence; Li, Shangzhong; Swann, Justine; Cowell, Annie; Zou, Bing Yu; Abdel- Haleem Mohamed, Alyaa; Villa-Galarce, Zaira; Moreno, Marta; Tong-Rios, Carlos; Vinetz, Joseph; Lewis, Nathan; Winzeler, Elizabeth A

    2017-01-01

    The exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.

  13. Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection

    KAUST Repository

    LaMonte, Gregory

    2017-10-03

    The exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.

  14. Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

    Science.gov (United States)

    Hage, Steffen R; Nieder, Andreas

    2015-05-06

    Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

  15. Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease.

    Science.gov (United States)

    Moro, Cécile; El Massri, Nabil; Darlot, Fannie; Torres, Napoleon; Chabrol, Claude; Agay, Diane; Auboiroux, Vincent; Johnstone, Daniel M; Stone, Jonathan; Mitrofanis, John; Benabid, Alim-Louis

    2016-10-01

    We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Similarity analysis between chromosomes of Homo sapiens and monkeys with correlation coefficient, rank correlation coefficient and cosine similarity measures

    OpenAIRE

    Someswara Rao, Chinta; Viswanadha Raju, S.

    2016-01-01

    In this paper, we consider correlation coefficient, rank correlation coefficient and cosine similarity measures for evaluating similarity between Homo sapiens and monkeys. We used DNA chromosomes of genome wide genes to determine the correlation between the chromosomal content and evolutionary relationship. The similarity among the H. sapiens and monkeys is measured for a total of 210 chromosomes related to 10 species. The similarity measures of these different species show the relationship b...

  17. Monkey alcohol tissue research resource: banking tissues for alcohol research.

    Science.gov (United States)

    Daunais, James B; Davenport, April T; Helms, Christa M; Gonzales, Steven W; Hemby, Scott E; Friedman, David P; Farro, Jonathan P; Baker, Erich J; Grant, Kathleen A

    2014-07-01

    An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is comorbid with damage to major organs including heart, lungs, liver, pancreas, and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of ethanol (EtOH) and they metabolize it more rapidly than primates. The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over long periods of time (12 to 30 months) with concomitant pathological changes in endocrine, hepatic, and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the EtOH-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. The MATRR is a unique postmortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer EtOH using a standardized experimental paradigm to the broader alcohol research community. This resource provides a translational platform from which we can better

  18. Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

    Science.gov (United States)

    Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

    2008-09-25

    Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

  19. Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    John K Thuita

    Full Text Available Novel drugs to treat human African trypanosomiasis (HAT are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (NECT to WHO Model Lists of Essential Medicines against second stage HAT, where parasites have invaded the central nervous system (CNS. The pharmacology of a potential orally available lead compound, N-methoxy-6-{5-[4-(N-methoxyamidino phenyl]-furan-2-yl}-nicotinamidine (DB844, was evaluated in a vervet monkey model of second stage HAT, following promising results in mice. DB844 was administered orally to vervet monkeys, beginning 28 days post infection (DPI with Trypanosoma brucei rhodesiense KETRI 2537. DB844 was absorbed and converted to the active metabolite 6-[5-(4-phenylamidinophenyl-furanyl-2-yl]-nicotinamide (DB820, exhibiting plasma C(max values of 430 and 190 nM for DB844 and DB820, respectively, after the 14th dose at 6 mg/kg qd. A 100-fold reduction in blood trypanosome counts was observed within 24 h of the third dose and, at the end of treatment evaluation performed four days post the last drug dose, trypanosomes were not detected in the blood or cerebrospinal fluid of any monkey. However, some animals relapsed during the 300 days of post treatment monitoring, resulting in a cure rate of 3/8 (37.5% and 3/7 (42.9% for the 5 mg/kg×10 days and the 6 mg/kg×14 days dose regimens respectively. These DB844 efficacy data were an improvement compared with pentamidine and pafuramidine both of which were previously shown to be non-curative in this model of CNS stage HAT. These data show that synthesis of novel diamidines with improved activity against CNS-stage HAT was possible.

  20. Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys

    Directory of Open Access Journals (Sweden)

    Alex G. Lee

    2016-06-01

    Full Text Available Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3 in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition. Striatal DRD2/3 availability in adulthood was measured in vivo by [11C]raclopride binding using positron emission tomography (PET. DRD2/3 availability was greater in caudate and putamen compared to ventral striatum as reported in PET studies of humans and other non-human primates. DRD2/3 availability in ventral striatum was also consistently greater in stress inoculated squirrel monkeys compared to no-stress controls. Squirrel monkeys exposed to stress inoculation in the presence of their mother did not differ from squirrel monkeys exposed to stress inoculation without maternal companionship. Similar effects in different social contexts extend the generality of our findings and together suggest that stress inoculation increases striatal DRD2/3 availability as a correlate of cognitive control in squirrel monkeys.

  1. Turnover of radio-iodinated and biosynthetically labelled fibrinogen in rhesus monkeys

    International Nuclear Information System (INIS)

    Moza, A.K.

    1982-01-01

    Successful radio-iodination of monkey fibrinogen using a previously documented method for rabbit fibrinogen is reported. The label was securely bound to fibrinogen without any evidence of polymerisation. Turnover rates and other kinetic parameters of fibrinogen using 125 I-fibrinogen have been compared with those obtained with biosynthetically labelled donor 75 Se-fibrinogen. Both studies yielded identical results. The values for normal monkeys showed a half life of 43.8 +- 1.03 h with 125 I-fibrinogen and 47.15 +- 1.24 with 75 Se-fibrinogen. The turnover rate of endogenous 75 Se-fibrinogen following administration of 75 Se-selenomethionine has also been studied. The half disappearance time value of 100.34 h was much longer than the t1/2 values obtained with either 125 I or 75 Se-fibrinogen. This is believed to be due the staggered input of fibrinogen molecules from the liver. (author)

  2. No evidence for neo-oogenesis may link to ovarian senescence in adult monkey.

    Science.gov (United States)

    Yuan, Jihong; Zhang, Dongdong; Wang, Lei; Liu, Mengyuan; Mao, Jian; Yin, Yu; Ye, Xiaoying; Liu, Na; Han, Jihong; Gao, Yingdai; Cheng, Tao; Keefe, David L; Liu, Lin

    2013-11-01

    Female germline or oogonial stem cells transiently residing in fetal ovaries are analogous to the spermatogonial stem cells or germline stem cells (GSCs) in adult testes where GSCs and meiosis continuously renew. Oocytes can be generated in vitro from embryonic stem cells and induced pluripotent stem cells, but the existence of GSCs and neo-oogenesis in adult mammalian ovaries is less clear. Preliminary findings of GSCs and neo-oogenesis in mice and humans have not been consistently reproducible. Monkeys provide the most relevant model of human ovarian biology. We searched for GSCs and neo-meiosis in ovaries of adult monkeys at various ages, and compared them with GSCs from adult monkey testis, which are characterized by cytoplasmic staining for the germ cell marker DAZL and nuclear expression of the proliferative markers PCNA and KI67, and pluripotency-associated genes LIN28 and SOX2, and lack of nuclear LAMIN A, a marker for cell differentiation. Early meiocytes undergo homologous pairing at prophase I distinguished by synaptonemal complex lateral filaments with telomere perinuclear distribution. By exhaustive searching using comprehensive experimental approaches, we show that proliferative GSCs and neo-meiocytes by these specific criteria were undetectable in adult mouse and monkey ovaries. However, we found proliferative nongermline somatic stem cells that do not express LAMIN A and germ cell markers in the adult ovaries, notably in the cortex and granulosa cells of growing follicles. These data support the paradigm that adult ovaries do not undergo germ cell renewal, which may contribute significantly to ovarian senescence that occurs with age. Copyright © 2013 AlphaMed Press.

  3. Topographic and age-related changes of the retinal epithelium and Bruch's membrane of rhesus monkeys.

    Science.gov (United States)

    Gouras, Peter; Ivert, Lena; Neuringer, Martha; Mattison, Julie A

    2010-07-01

    To examine structural differences in the retinal pigmented epithelium (RPE) and Bruch's membrane of rhesus monkeys (Macaca mulatta) as a function of topography and age. The retinas of two old (24 and 26 years old) and two young (1 and 6 years old) female monkeys were examined by light fluorescence and electron microscopy at the macula, equator, and ora serrata. All monkeys lacked fluorescence and lipofuscin granules in the RPE at the ora serrata where photoreceptors are absent. The equator and macula showed intense fluorescence and many lipofuscin granules in the RPE of the old but not the young monkeys. At the ora, the RPE contained many dense round melanin granules throughout the cell. At the equator and macula, melanin granules were more apical, less frequent, and often elongated. Mitochondria were clustered at the basal side of the RPE cell near infolds of the plasma membrane. Both mitochondria and infolds tended to increase toward the macula. In all regions, the basal lamina of the RPE did not penetrate the extracellular space adjacent to infolds. The elastin layer of Bruch's membrane was wide at the ora and equator and thinner at the macula. In the old monkeys, drusen were found at all retinal regions between the basal lamina and the internal collagen layer of Bruch's membrane. The drusen were often membrane-bound with a basal lamina and contained material resembling structures in the RPE. Lack of fluorescence and lipofuscin in the RPE at the ora serrata, where photoreceptors are absent, confirms that RPE fluorescence occurs only where outer segments are phagocytized. Mitochondrial clustering indicates that the basal side of the RPE cell uses the most energy and this becomes maximal at the macula. The presence of age-related degenerative changes and drusen at all retinal locations in the older monkeys, even at the ora where RPE lipofuscin was absent, indicates that these processes are not dependent on local lipofuscin accumulation. Therefore lipofuscin

  4. Tuberculosis Caused by Mycobacterium orygis in Dairy Cattle and Captured Monkeys in Bangladesh: a New Scenario of Tuberculosis in South Asia.

    Science.gov (United States)

    Rahim, Z; Thapa, J; Fukushima, Y; van der Zanden, A G M; Gordon, S V; Suzuki, Y; Nakajima, C

    2017-12-01

    Mycobacterium orygis, commonly known as the oryx bacillus and a newly proposed Mycobacterium tuberculosis complex subspecies, was isolated from 18 cattle in a dairy farm and two captured rhesus monkeys in a zoo in Bangladesh. All the infected animals had tuberculosis lesions in their lungs, suggesting transmission and infection with M. orygis by an airborne route. The 20 isolates were analysed using a range of conventional and molecular typing methods, and RD-deletion typing and sequencing of selected genes confirmed the isolates as M. orygis. Multiple-locus variable-number tandem repeat analysis (MLVA) allowed the isolates to be divided into three clusters based on the relatedness of their MLVA profiles. The two monkey isolates shared the same MLVA pattern with 15 of the cattle isolates, whereas the remaining three cattle isolates had different patterns, even though the latter animals had been kept in the same dairy farm. The diversity observed among isolates may suggest the bacteria have been established in this area for a long period. This study along with other recent findings that report the detection of M. orygis from animals as well as humans originating from South Asia potentially indicate endemic distribution of M. orygis in South Asia. © 2016 Blackwell Verlag GmbH.

  5. Can human eyes prevent perceptual narrowing for monkey faces in human infants?

    Science.gov (United States)

    Damon, Fabrice; Bayet, Laurie; Quinn, Paul C; Hillairet de Boisferon, Anne; Méary, David; Dupierrix, Eve; Lee, Kang; Pascalis, Olivier

    2015-07-01

    Perceptual narrowing has been observed in human infants for monkey faces: 6-month-olds can discriminate between them, whereas older infants from 9 months of age display difficulty discriminating between them. The difficulty infants from 9 months have processing monkey faces has not been clearly identified. It could be due to the structural characteristics of monkey faces, particularly the key facial features that differ from human faces. The current study aimed to investigate whether the information conveyed by the eyes is of importance. We examined whether the presence of Caucasian human eyes in monkey faces allows recognition to be maintained in 6-month-olds and facilitates recognition in 9- and 12-month-olds. Our results revealed that the presence of human eyes in monkey faces maintains recognition for those faces at 6 months of age and partially facilitates recognition of those faces at 9 months of age, but not at 12 months of age. The findings are interpreted in the context of perceptual narrowing and suggest that the attenuation of processing of other-species faces is not reversed by the presence of human eyes. © 2015 Wiley Periodicals, Inc.

  6. Selection and Pairing of ’Normal’ Rhesus Monkeys (Macaca mulatta) for Research.

    Science.gov (United States)

    1978-11-08

    week intervals. Fecal bacteriological cultures did not detect any Salmonella or Shigella car- riers in the population. The male monkeys ranged in age...1Special Roert 78-6 LVEL•$ SELECTION AND PAIRING OF "NORMAL" RHESUS MONKEYS (Macaca mulatto) FOR RESEARC Matthew J. Kessler, James L. Kupper, James D...public release; distribution unlimited. SELECTION AND PAIRING OF "NORMAL" RHESUS MONKEYS (Macaca mulatta) FOR RESEARCH Matthew J. Kessler, James L

  7. Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

    Science.gov (United States)

    Souquière, Sandrine; Makuwa, Maria; Sallé, Bettina; Lepelletier, Yves; Mortreux, Franck; Hermine, Olivier; Kazanji, Mirdad

    2014-04-01

    Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. PET study of the distribution of [11C]fluoxetine in a monkey brain

    International Nuclear Information System (INIS)

    Shiue, C.-Y.; Shiue, Grace G.; Cornish, Kurtis G.; O'Rourke, Maria F.

    1995-01-01

    No-carrier-added [ 11 C]fluoxetine (2) was synthesized by methylation of norfluoxetine (1) with [ 11 C]H 3 I in 20% radiochemical yield in a synthesis time of 40 min from EOB with a specific activity of 0.48 Ci/μM (EOB). In vivo study in mouse indicated that the uptake of 2 in mouse tissues was high and the radioactivity remained constant throughout the study. The uptake of 2 in mouse brain was 4%/g. PET study in a Rhesus monkey also showed that the uptakes of 2 in different brain regions were similar and the retention of radioactivity in these regions remained constant throughout the study (80 min). Analysis of arterial plasma by HPLC showed that only 20% of radioactivity in the plasma remained as 2 at 30 min post-injection. These results suggest that the uptake of fluoxetine in monkey brain is probably not receptor mediated. Rather, blood flow, lipophilicity or other transport mechanisms may play a role in its uptake

  9. Four stimulants of the central nervous system: effects on short-term memory in young versus aged monkeys.

    Science.gov (United States)

    Bartus, R T

    1979-07-01

    Aged Rhesus monkeys and young control monkeys were tested in a delayed-response procedure to assess the effects of central-nervous-system (CNS) stimulants on short-term memory (STM). Previous research had established that the aged monkeys showed specific impairments of STM in this procedure. Four different CNS stimulants (methylphenidate, magnesium pemoline, a pentylenetetrazole/niacin mixture, and caffeine) were chosen for evaluation on the basis of their relevancy to current geriatric-psychopharmacologic research. Four different doses of each of the four CNS stimulants were given to each monkey, counter-balanced for possible order effects. Methylphenidate and caffeine impaired the performance of both age groups in this non-human primate cognitive task, even at relatively low dose levels. Magnesium pemoline produced fewer adverse effects and some evidence of improving STM in the aged monkeys, although not within the levels of statistical significance. The pentylenetetrazole/niacin mixture produced a three-way interaction involving age, dose and retention interval. This reflected the fact that although no definite effects were noted under the zero-sec control condition, statistically significant age-related deficits did occur in the STM-dependent retention interval as the dose varied. The data demonstrate that, of these four CNS stimulants, none radily improves (and often may impair) performance of tasks requiring STM. Thus the results of this study offer little support for the hypothesis that general CNS stimulation may constitute significant therapy for cognitive impairments associated with advanced age.

  10. Metabolic changes in the visual cortex of binocular blindness macaque monkeys: a proton magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Lingjie Wu

    Full Text Available PURPOSE: To evaluate proton magnetic resonance spectroscopy ((1H-MRS in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys. MATERIALS AND METHODS: Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B to obtain binocular blindness. Two healthy macaque monkeys served as a control group (group A. After sixteen months post-procedure, (1H-MRS was performed in the visual cortex of all monkeys. We compared the peak areas of NAA, Cr, Cho, Glx and Ins and the ratios of NAA/Cr, Cho/Cr, Glx/Cr and Ins/Cr of each monkey in group B with group A. RESULTS: The peak area of NAA and the NAA/Cr ratio in the visual cortex of monkey 4 in group B were found to be dramatically decreased, the peak area of NAA slightly decreased and the NAA/Cr ratio clearly decreased in visual cortex of monkey 3 in group B than those in group A. The peak area of Ins and the Ins/Cr ratio in the visual cortex of monkey 4 in group B slightly increased. The peak area of Cho and the Cho/Cr ratio in the visual cortex of all monkeys in group B dramatically increased compared with group A. The peak area of Glx in the visual cortex of all monkeys in group B slightly increased compared with group A. CONCLUSIONS: (1H-MRS could detect biochemical and metabolic changes in the visual cortex and therefore this technique can be used to provide valuable information for investigating the mechanisms of cross-modal plasticity of binocular blindness in a macaque monkey model.

  11. Behavioural Responses of Yunnan Snub-Nosed Monkeys (Rhinopithecus bieti) to Tourists in a Provisioned Monkey Group in Baimaxueshan Nature Reserve.

    Science.gov (United States)

    Xia, Wancai; Ren, Baoping; Li, Yanhong; Hu, Jie; He, Xinming; Krzton, Ali; Li, Ming; Li, Dayong

    2016-01-01

    The appearance of tourists brings about behavioural changes in some primates. Primate behavioural responses to human activities can reflect their survival strategy. Little is known about how the behaviour of Rhinopithecus bieti changes in the presence of tourists. Here we provide the first detailed description of interactions between a provisioned group of R. bieti and tourists at Xiangguqing in Baimaxueshan Nature Reserve from July 2012 to June 2013. We found that R. bieti had different response rates to the 5 most common human actions (shout, photograph, offer food, clap, and wave). Results indicated that R. bieti expresses 10 behavioural reactions (threat, escape, vigilance, warning, panic, alliance, attack, foraging, approach, and staring) to tourists' actions. On the whole, most of the monkeys' responses were unfriendly or hostile; a small number were neutral and affiliative. Behavioural responses were also significantly different among the different age/sex classes. Immature individuals engaged in more affiliative behaviours than adult individuals, and adult males tended towards more hostile behaviours. The behaviour of R. bieti towards tourists showed both tension and adaptability. Scientific management of provisioned monkey groups and strict regulation of tourist behaviour is needed in order to protect the animals from the negative effects of tourism-related disturbance. © 2017 S. Karger AG, Basel.

  12. Can monkeys make investments based on maximized pay-off?

    Directory of Open Access Journals (Sweden)

    Sophie Steelandt

    2011-03-01

    Full Text Available Animals can maximize benefits but it is not known if they adjust their investment according to expected pay-offs. We investigated whether monkeys can use different investment strategies in an exchange task. We tested eight capuchin monkeys (Cebus apella and thirteen macaques (Macaca fascicularis, Macaca tonkeana in an experiment where they could adapt their investment to the food amounts proposed by two different experimenters. One, the doubling partner, returned a reward that was twice the amount given by the subject, whereas the other, the fixed partner, always returned a constant amount regardless of the amount given. To maximize pay-offs, subjects should invest a maximal amount with the first partner and a minimal amount with the second. When tested with the fixed partner only, one third of monkeys learned to remove a maximal amount of food for immediate consumption before investing a minimal one. With both partners, most subjects failed to maximize pay-offs by using different decision rules with each partner' quality. A single Tonkean macaque succeeded in investing a maximal amount to one experimenter and a minimal amount to the other. The fact that only one of over 21 subjects learned to maximize benefits in adapting investment according to experimenters' quality indicates that such a task is difficult for monkeys, albeit not impossible.

  13. Absorption of topically applied hydrocortisone from the eye of the rhesus monkey

    International Nuclear Information System (INIS)

    Oehman, L.; Johansson, E.D.B.; Edqvist, L.-E.

    1982-01-01

    Blood samples were collected from anaesthetized monkeys during one h a) afer topical application of an eyedrop of hydrocortisone acetate suspension, b) after topical application of a drop of the vehicle alone, and c) after no application at all. Radioimmunoassay (RIA) showed a rapid and similar increase of hydrocortisone plasma levels in all 3 kinds of experiments. RIA revealed that in monkeys the anaesthetic procedure alone was sufficient to cause a considerable increase of endogenous hydrocortisone levels overshadowing any systemic absorption of topical hydrocortisone. Using tritiated hydrocortisone instead a rapid increase of systemic absorption after topical application was found. A plasma concentration of 1% of the dose was found one min after topical instillation incresing to a maximum of 6-7% at 30 min. The half time of the slow phase of elimination was about 19 h. (author)

  14. Streptococcus oralis cerebral abscess following monkey bite in a 2-month-old infant.

    Science.gov (United States)

    Thiagarajan, Srinivasan; Krishnamurthy, Sriram; Raghavan, Renitha; Mahadevan, Subramanian; Madhugiri, Venkatesh S; Sistla, Sujatha

    2016-05-01

    Although cerebral abscesses caused by animal bites have been reported, they are extremely rare in infants and have not been described following monkey bite. A 55-day-old male infant presented with a multi-loculated Streptococcus oralis cerebral abscess following a monkey bite on the scalp. There was a clinical response to antibiotic therapy and repeated surgical aspiration followed by a ventriculoperitoneal shunt. This is the first report of a patient with a brain abscess following a monkey bite.

  15. Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

    Science.gov (United States)

    Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

    2015-01-01

    Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in

  16. Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

    Directory of Open Access Journals (Sweden)

    Katharina Debowski

    Full Text Available Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80 and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement

  17. Activity of two chlorinated lincomycin analogues against chloroquine-resistant falciparum malaria in owl monkeys.

    Science.gov (United States)

    Powers, K G; Jacobs, R L

    1972-01-01

    The chloroquine-resistant Oak Knoll strain of Plasmodium falciparum, recently adapted to the owl monkey (Aotus trivirgatus), was insusceptible to chloroquine therapy. Two chlorinated lincomycin analogues tested in this host-parasite system cured blood-induced infections. Acute infections were treated orally for 7 consecutive days with either 15 or 75 mg of clindamycin hydrochloride (U-21) per kg per day, 10 or 50 mg of N-demethyl-4'-pentyl clindamycin hydrochloride (U-24) per kg per day, or 20 mg of chloroquine base per kg per day. These lincomycin analogues cleared trophozoites from the peripheral blood by the end of the 7-day treatment period. The speed of clearance of parasites was not dose-related, but curative activity appeared dependent upon the amount of drug given as well as the number of daily treatments. The efficacy of U-21 and U-24 is of particular interest since they represent major structural departures from compounds commonly used in the treatment of malaria.

  18. jMonkeyEngine 3.0 cookbook

    CERN Document Server

    Edén, Rickard

    2014-01-01

    If you are a jMonkey developer or a Java developer who is interested to delve further into the game making process to expand your skillset and create more technical games, then this book is perfect for you.

  19. Reproductive function of monkeys subjected to chronic irradiation

    International Nuclear Information System (INIS)

    Artem'eva, N.S.; Kosichenko, L.P.; Andreeva, A.V.; Zvereva, G.A.

    1976-01-01

    Marked functional disorders have been detected in reproductive glands of eight female monkeys (as compared to twelve control animals) subjected to protracted (up to eight years) irradiation (cumulative doses 826-3282 R). Irradiated monkeys exhibited a drastically decreased reproductive capacity, early menopause and sterility. Irradiation of preadolescent animals inhibited, in most cases, the puberty processes and disturbed sex cycles. Structural disorders in sex glands, inhibition of the processes of maturation and ovulation of folloculi, death of the mass of germ cells, atypical vegetations of the integmentary epithelium, sclerosing and cystic degeneration of the glandular tissue have been revealed

  20. Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

    Science.gov (United States)

    Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

    2013-12-01

    Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

  1. Rod photoreceptors express GPR55 in the adult vervet monkey retina

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

    2013-01-01

    . Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its neural (cone photoreceptor, horizontal, bipolar, amacrine and ganglion cells) and CB2R in glial...

  2. Traditions in spider monkeys are biased towards the social domain.

    Directory of Open Access Journals (Sweden)

    Claire J Santorelli

    Full Text Available Cross-site comparison studies of behavioral variation can provide evidence for traditions in wild species once ecological and genetic factors are excluded as causes for cross-site differences. These studies ensure behavior variants are considered within the context of a species' ecology and evolutionary adaptations. We examined wide-scale geographic variation in the behavior of spider monkeys (Ateles geoffroyi across five long-term field sites in Central America using a well established ethnographic cross-site survey method. Spider monkeys possess a relatively rare social system with a high degree of fission-fusion dynamics, also typical of chimpanzees (Pan troglodytes and humans (Homo sapiens. From the initial 62 behaviors surveyed 65% failed to meet the necessary criteria for traditions. The remaining 22 behaviors showed cross-site variation in occurrence ranging from absent through to customary, representing to our knowledge, the first documented cases of traditions in this taxon and only the second case of multiple traditions in a New World monkey species. Of the 22 behavioral variants recorded across all sites, on average 57% occurred in the social domain, 19% in food-related domains and 24% in other domains. This social bias contrasts with the food-related bias reported in great ape cross-site comparison studies and has implications for the evolution of human culture. No pattern of geographical radiation was found in relation to distance across sites. Our findings promote A. geoffroyi as a model species to investigate traditions with field and captive based experiments and emphasize the importance of the social domain for the study of animal traditions.

  3. Species-specific calls evoke asymmetric activity in the monkey's temporal poles.

    Science.gov (United States)

    Poremba, Amy; Malloy, Megan; Saunders, Richard C; Carson, Richard E; Herscovitch, Peter; Mishkin, Mortimer

    2004-01-29

    It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions. Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations. To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere.

  4. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    International Nuclear Information System (INIS)

    Gautier, Jean-Charles; Zhou, Xiaobing; Yang, Yi; Gury, Thierry; Qu, Zhe; Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz; Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas; Zhang, Tianyi; Wang, Jufeng; Detilleux, Philippe; Li, Bo

    2016-01-01

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

  5. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    Energy Technology Data Exchange (ETDEWEB)

    Gautier, Jean-Charles, E-mail: jean-charles.gautier@sanofi.com [Sanofi R& D, Vitry-sur-Seine (France); Zhou, Xiaobing [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Yang, Yi [Sanofi R& D, Bridgewater (United States); Gury, Thierry [Sanofi R& D, Vitry-sur-Seine (France); Qu, Zhe [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz [Sanofi R& D, Vitry-sur-Seine (France); Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas [Natural and Medical Sciences Institute at the University Tübingen (Germany); Zhang, Tianyi [Frontage Laboratories, Shanghai (China); Wang, Jufeng [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China); Detilleux, Philippe [Sanofi R& D, Vitry-sur-Seine (France); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs (NCSED), National Institutes for Food and Drug Control, Beijing (China)

    2016-07-15

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

  6. Evaluation of the differences of myocardial fibers between acute and chronic myocardial infarction: Application of diffusion tensor magnetic resonance imaging INA Rhesus monkey model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu Qing; Cai, Wei; Wang, Lei; Xia, Rui; Chen, Wei; Zheng, Jie [Dept. of Radiology, West China Hospital, Sichuan University, Sichuan (China); Gao, Fabao [Mallinckrodt Institute of Radiology, School of Medicine, Washington University, St. Louis (United States)

    2016-09-15

    To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI. Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10{sup -4} mm{sup 2}/s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10{sup -4} mm{sup 2}/s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°–11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°–53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°–66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°–64.9 ± 4.3°). Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models.

  7. Evaluation of the differences of myocardial fibers between acute and chronic myocardial infarction: Application of diffusion tensor magnetic resonance imaging INA Rhesus monkey model

    International Nuclear Information System (INIS)

    Wang, Yu Qing; Cai, Wei; Wang, Lei; Xia, Rui; Chen, Wei; Zheng, Jie; Gao, Fabao

    2016-01-01

    To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI. Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10 -4 mm 2 /s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10 -4 mm 2 /s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°–11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°–53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°–66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°–64.9 ± 4.3°). Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models

  8. Radiation-induced chromosome aberrations in lymphocytes from man and crab-eating monkey

    International Nuclear Information System (INIS)

    Takahashi, E.; Hirai, M.; Tobari, I.; Utsugi, T.; Nakai, S.

    1982-01-01

    To obtain information on the relation between yield of chromosome aberrations and dose at low-dose levels, experiments were conducted with 5, 10, 20, 30 and 50 rad of 137 Cs γ-rays, on lymphocytes from man and crab-eating monkey (Macaca fascicularis). The dose-response relationship for dicentrics was obtained from the combined data of these low-dose experiments with those of our previous ones at high doses (100-400 rad). When the difference between observed yields and those expected from the linear-quadratic model were computed, the dose-response curve had a good fit for man, but not for the monkey. The linear regression lines between 0 and 30 rad were calculated, because the expected values of α/β for man and monkey would be about 100 and 60 rad. The human data gave a satisfactory fit to a linear model, i.e., a linear increase in aberration frequency with dose, whereas this was not so for those of the monkey. Furthermore, there was some suggestive evidence for the existence of a plateau in dicentric yields between 10 and 30 rad for the monkey and between 20 and 30 rad for human lymphocytes, but more data would be needed to verify this suggestion, particularly for human lymphocytes. (orig.)

  9. The Moral Lives of Laboratory Monkeys: Television and the Ethics of Care.

    Science.gov (United States)

    Sharp, Lesley A

    2017-06-01

    Why do lab monkeys watch TV? This essay examines the preponderance of televisions in primate housing units based in academic research laboratories. Within such labs, television and related visual media are glossed as part-and-parcel of welfare or species-specific enrichment practices intended for research monkeys, a logic that is simultaneously historically- and ontologically-based. In many research centers, television figures prominently in the two inseparable domains of a lab monkey's life: as a research tool employed during experiments, and in housing units where captive monkeys are said to enjoy watching TV during "down time." My purpose is not to determine whether monkeys do indeed enjoy, or need, television; rather, I employ visual media as a means to uncover, and decipher, the moral logic of an ethics of care directed specifically at highly sentient creatures who serve as human proxies in a range of experimental contexts. I suggest that this specialized ethics of animal care materializes Mattingly's notion of "moral laboratories" (Mattingly in Moral laboratories: family peril and the struggle for a good life, University of California Press, Berkeley, 2014), where television mediates the troublesome boundary of species difference among the simian and human subjects who cohabit laboratory worlds.

  10. Telemetric assessment of social and single housing: Evaluation of electrocardiographic intervals in jacketed cynomolgus monkeys.

    Science.gov (United States)

    Kaiser, Robert A; Tichenor, Stephen D; Regalia, Douglas E; York, Kristina; Holzgrefe, Henry H

    2015-01-01

    Proactive efforts to socially house laboratory animals are a contemporary, important focus for enhancing animal welfare. Jacketing cynomolgus monkeys has been traditionally considered an exclusionary criterion for social housing based on unsubstantiated concerns that study conduct or telemetry equipment might be compromised. Our objective was to evaluate the effects of jacketing naïve, adolescent cynomolgus monkeys in different single and social housing types based on parallel comparisons of heart rate. Eight naive cynomolgus monkeys were randomized into pairs and ECG data were collected for 24h from each animal in each housing condition using a crossover design. Caging paradigms consisted of standard individual, standard pair, quaternary pair (4 linked cages), and European-style pair housing in non-sequential order varied by pair to control for possible time bias. Dosing and blood collection procedures were performed to characterize any effects of housing on ECG data during study conduct. There was no increase in the incidence of equipment damage in pair vs. individually housed animals. Further, animals in all 4 housing paradigms showed similar acclimation assessed as heart rate (mean 139-154 beats per minute), and maintained similar diurnal rhythms, with an expected slowing of the heart rate at night (aggregate lights out HR 110±4bpm compared to daytime 146±7bpm). This study demonstrates the effects of different social access and housing types on the study-naïve cynomolgus monkeys during jacketed cardiovascular telemetry data collection in a repeat-dose toxicology study design. There were no discernible effects of social housing on baseline ECG parameters collected via jacketed telemetry, and all animals maintained expected diurnal rhythms in all housing settings tested. These data demonstrate that cynomolgus monkeys can be socially housed during data collection as a standard practice, consistent with global efforts to improve study animal welfare. Copyright

  11. Differences in behaviour and physiology between adult surrogate-reared and mother-reared Cynomolgous monkeys (Macaca fascicularis)

    NARCIS (Netherlands)

    Luijk, I.A.F. van; Timmermans, P.J.A.; Sweep, C.G.J.; Willems, J.; Vossen, J.M.H.

    2000-01-01

    Previous studies of the effects of rearing conditions on exploratory behaviour revealed that 80% of monkeys reared in peer groups with surrogate mothers developed neophobia, whereas only 15 % of mother-reared monkeys did. Young surrogate-reared and, especially, isolated rhesus monkeys are known to

  12. Vestibulo-ocular reflex of the squirrel monkey during eccentric rotation with centripetal acceleration along the naso-occipital axis

    Science.gov (United States)

    Merfeld, D. M.; Paloski, W. H. (Principal Investigator)

    1996-01-01

    The vestibulo-ocular reflexes (VOR) are determined not only by angular acceleration, but also by the presence of gravity and linear acceleration. This phenomenon was studied by measuring three-dimensional nystagmic eye movements, with implanted search coils, in four male squirrel monkeys. Monkeys were rotated in the dark at 200 degrees/s, centrally or 79 cm off-axis, with the axis of rotation always aligned with gravity and the spinal axis of the upright monkeys. The monkey's position relative to the centripetal acceleration (facing center or back to center) had a dramatic influence on the VOR. These studies show that a torsional response was always elicited that acted to shift the axis of eye rotation toward alignment with gravito-inertial force. On the other hand, a slow phase downward vertical response usually existed, which shifted the axis of eye rotation away from the gravito-inertial force. These findings were consistent across all monkeys. In another set of tests, the same monkeys were rapidly tilted about their interaural (pitch) axis. Tilt orientations of 45 degrees and 90 degrees were maintained for 1 min. Other than a compensatory angular VOR during the rotation, no consistent eye velocity response was ever observed during or following the tilt. The absence of any response following tilt proves that the observed torsional and vertical responses were not a positional nystagmus. Model simulations qualitatively predict all components of these eccentric rotation and tilt responses. These simulations support the conclusion that the VOR during eccentric rotation may consist of two components: a linear VOR and a rotational VOR. The model predicts a slow phase downward, vertical, linear VOR during eccentric rotation even though there was never a change in the force aligned with monkey's spinal (Z) axis. The model also predicts the torsional components of the response that shift the rotation axis of the angular VOR toward alignment with gravito-inertial force.

  13. Exploring the extent and function of higher-order auditory cortex in rhesus monkeys.

    Science.gov (United States)

    Poremba, Amy; Mishkin, Mortimer

    2007-07-01

    Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques, cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left-hemisphere "dominance" during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole "dominance" appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys.

  14. Monkey prefrontal neurons during Sternberg task performance: full contents of working memory or most recent item?

    Science.gov (United States)

    Konecky, R O; Smith, M A; Olson, C R

    2017-06-01

    To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or

  15. Same/different concept learning by capuchin monkeys in matching-to-sample tasks.

    Directory of Open Access Journals (Sweden)

    Valentina Truppa

    Full Text Available The ability to understand similarities and analogies is a fundamental aspect of human advanced cognition. Although subject of considerable research in comparative cognition, the extent to which nonhuman species are capable of analogical reasoning is still debated. This study examined the conditions under which tufted capuchin monkeys (Cebus apella acquire a same/different concept in a matching-to-sample task on the basis of relational similarity among multi-item stimuli. We evaluated (i the ability of five capuchin monkeys to learn the same/different concept on the basis of the number of items composing the stimuli and (ii the ability to match novel stimuli after training with both several small stimulus sets and a large stimulus set. We found the first evidence of same/different relational matching-to-sample abilities in a New World monkey and demonstrated that the ability to match novel stimuli is within the capacity of this species. Therefore, analogical reasoning can emerge in monkeys under specific training conditions.

  16. Same/Different Concept Learning by Capuchin Monkeys in Matching-to-Sample Tasks

    Science.gov (United States)

    Truppa, Valentina; Piano Mortari, Eva; Garofoli, Duilio; Privitera, Sara; Visalberghi, Elisabetta

    2011-01-01

    The ability to understand similarities and analogies is a fundamental aspect of human advanced cognition. Although subject of considerable research in comparative cognition, the extent to which nonhuman species are capable of analogical reasoning is still debated. This study examined the conditions under which tufted capuchin monkeys (Cebus apella) acquire a same/different concept in a matching-to-sample task on the basis of relational similarity among multi-item stimuli. We evaluated (i) the ability of five capuchin monkeys to learn the same/different concept on the basis of the number of items composing the stimuli and (ii) the ability to match novel stimuli after training with both several small stimulus sets and a large stimulus set. We found the first evidence of same/different relational matching-to-sample abilities in a New World monkey and demonstrated that the ability to match novel stimuli is within the capacity of this species. Therefore, analogical reasoning can emerge in monkeys under specific training conditions. PMID:21858225

  17. Effects of anesthesia upon 18F-FDG uptake in rhesus monkey brains

    International Nuclear Information System (INIS)

    Itoh, Takashi; Wakahara, Shunichi; Nakano, Takayuki; Suzuki, Kazutoshi; Kobayashi, Kaoru; Inoue, Osamu

    2005-01-01

    The kinetics of 18 F-fluorodeoxyglucose ( 18 F-FDG) in the monkey brain were monitored, and comparisons were made between the conscious state and when under ketamine and pentobarbital anesthesia. Rhesus monkeys were intravenously injected with 18 F-FDG and followed by 60 min of PET scanning. In the conscious state, the 18 F-FDG concentration reached a plateau 5 min after intravenous injection. Under ketamine anesthesia, the 18 F-FDG concentration gradually increased with time in all monitored regions. At 60 min after injection, the concentration in the striatum was about 3.2 times greater than that in the conscious state, and about 4.5 times greater in the cerebral cortex. Under pentobarbital anesthesia, the 18 F-FDG concentration in the occipital cortex was slightly lower. These findings demonstrate that 18 F-FDG concentration in the monkey brain is significantly affected by anesthesia. The results also imply the existence of a short-term regulation mechanism for hexokinase activity in intact monkey brain. (author)

  18. The ability of multimerized cyclophilin A to restrict retrovirus infection

    International Nuclear Information System (INIS)

    Javanbakht, Hassan; Diaz-Griffero, Felipe; Yuan Wen; Yeung, Darwin F.; Li Xing; Song Byeongwoon; Sodroski, Joseph

    2007-01-01

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection

  19. Third-party social evaluations of humans by monkeys and dogs.

    Science.gov (United States)

    Anderson, James R; Bucher, Benoit; Chijiiwa, Hitomi; Kuroshima, Hika; Takimoto, Ayaka; Fujita, Kazuo

    2017-11-01

    Developmental psychologists are increasingly interested in young children's evaluations of individuals based on third-party interactions. Studies have shown that infants react negatively to agents who display harmful intentions toward others, and to those who behave unfairly. We describe experimental studies of capuchin monkeys' and pet dogs' differential reactions to people who are helpful or unhelpful in third-party contexts, and monkeys' responses to people who behave unfairly in exchanges of objects with a third party. We also present evidence that capuchin monkeys monitor the context of failures to help and violations of reciprocity, and that intentionality is one factor underlying their social evaluations of individuals whom they see interacting with others. We conclude by proposing some questions for studies of nonhuman species' third party-based social evaluations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Standardized Full-Field Electroretinography in the Green Monkey (Chlorocebus sabaeus)

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Javadi, Pasha; Palmour, Roberta M

    2014-01-01

    Full-field electroretinography is an objective measure of retinal function, serving as an important diagnostic clinical tool in ophthalmology for evaluating the integrity of the retina. Given the similarity between the anatomy and physiology of the human and Green Monkey eyes, this species has......). Photopic and scotopic ERG recordings were obtained by full-field stimulation over a range of 6 log units of intensity in dark-adapted or light-adapted eyes of adult Green Monkeys (Chlorocebus sabaeus). Intensity, duration, and interval of light stimuli were varied separately. Reproducible values...... of amplitude and latency were obtained for the a- and b-waves, under well-controlled adaptation and stimulus conditions; the i-wave was also easily identifiable and separated from the a-b-wave complex in the photopic ERG. The recordings obtained in the healthy Green Monkey matched very well with those...

  1. Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin.

    Science.gov (United States)

    Lee, Youngjeon; Kim, Young-Hyun; Park, Sang-Je; Huh, Jae-Won; Kim, Sang-Hyun; Kim, Sun-Uk; Kim, Ji-Su; Jeong, Kang-Jin; Lee, Kyoung-Min; Hong, Yonggeun; Lee, Sang-Rae; Chang, Kyu-Tae

    2014-01-01

    We reported previously that the intracerebroventricular streptozotocin (icv-STZ)-treated cynomolgus monkey showed regionally specific glucose hypometabolism in FDG-PET imaging, similar to that observed in the early stages of sporadic Alzheimer's disease (sAD). However, further pathological analyses of this model at the molecular level are needed to validate it as a feasible model for sAD. Two cynomolgus monkeys were injected with 2 mg/kg STZ into the cerebellomedullary cistern at day 1, 7 and 14. Two control monkeys were given normal saline. At 5 months after injection, the expression levels of genes encoding 9 upstream molecules in insulin/insulin-like growth factor (IGF) signaling and markers for 4 cell-type populations in the frontal cortex, hippocampus, posterior cingulate, precuneus, and occipital cortex of control and icv-STZ treated cynomolgus monkeys were examined. Real-time quantitative PCR analyses demonstrated that the overall mRNA expression of insulin/IGF signaling-related genes was mainly impaired in the anterior part of the cerebrum, frontal cortex, and hippocampus, similar to the early stage of sAD. The changes were accompanied by the loss of oligodendrocytes and neurons. The posterior part of the cerebrum did not show degenerative alterations. The present study provides important fundamental information on the icv-STZ monkey model for sAD. These results may help guide future studies using this model for the investigation of pathological mechanisms and the development of drugs for sAD.

  2. Endogenous New World primate type C viruses isolated from owl monkey (Aotus trivirgatus) kidney cell line.

    Science.gov (United States)

    Todaro, G J; Sherr, C J; Sen, A; King, N; Daniel, M D; Fleckenstein, B

    1978-01-01

    A type C virus (OMC-1) detected in a culture of owl monkey kidney cells resembled typical type C viruses morphologically, but was slightly larger than previously characterized mammalian type C viruses. OMC-1 can be transmitted to bat lung cells and cat embryo fibroblasts. The virions band at a density of 1.16 g/ml in isopycnic sucrose density gradients and contain reverse transcriptase and a 60-65S RNA genome composed of approximately 32S subunits. The reverse transcriptase is immunologically and biochemically distinct from the polymerases of othe retroviruses. Radioimmunoassays directed to the interspecies antigenic determinants of the major structure proteins of other type C viruses do not detect a related antigen in OMC-1. Nucleic acid hybridization experiments using labeled viral genomic RNA or proviral cDNA transcripts to normal cellular DNA of different species show that OMC-1 is an endogenous virus with multiple virogene copies (20-50 per haploid genome) present in normal owl monkey cells and is distinct from previously isolated type C and D viruses. Sequences related to the OMC-1 genome can be detected in other New World monkeys. Thus, similar to the Old World primates (e.g., baboons as a prototype), the New World monkeys contain endogenous type C viral genes that appear to have been transmitted in the primate germ line. Images PMID:76312

  3. High population density of black-handed spider monkeys (Ateles geoffroyi) in Costa Rican lowland wet forest.

    Science.gov (United States)

    Weghorst, Jennifer A

    2007-04-01

    The main objective of this study was to estimate the population density and demographic structure of spider monkeys living in wet forest in the vicinity of Sirena Biological Station, Corcovado National Park, Costa Rica. Results of a 14-month line-transect survey showed that spider monkeys of Sirena have one of the highest population densities ever recorded for this genus. Density estimates varied, however, depending on the method chosen to estimate transect width. Data from behavioral monitoring were available to compare density estimates derived from the survey, providing a check of the survey's accuracy. A combination of factors has most probably contributed to the high density of Ateles, including habitat protection within a national park and high diversity of trees of the fig family, Moraceae. Although natural densities of spider monkeys at Sirena are substantially higher than those recorded at most other sites and in previous studies at this site, mean subgroup size and age ratios were similar to those determined in previous studies. Sex ratios were similar to those of other sites with high productivity. Although high densities of preferred fruit trees in the wet, productive forests of Sirena may support a dense population of spider monkeys, other demographic traits recorded at Sirena fall well within the range of values recorded elsewhere for the species.

  4. Pharmacokinetics and enhanced bioavailability of candidate cancer preventative agent, SR13668 in dogs and monkeys.

    Science.gov (United States)

    Kapetanovic, Izet M; Muzzio, Miguel; Hu, Shu-Chieh; Crowell, James A; Rajewski, Roger A; Haslam, John L; Jong, Ling; McCormick, David L

    2010-05-01

    SR13668 (2,10-dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3-b)carbazole), is a new candidate cancer chemopreventive agent under development. It was designed using computational modeling based on a naturally occurring indole-3-carbinol and its in vivo condensation products. It showed promising anti-cancer activity and its preclinical toxicology profile (genotoxicity battery and subchronic rat and dog studies) was unremarkable. However, it exhibited a very poor oral bioavailability (Solutol, were tested in dogs and monkeys. Levels of SR13668 were measured in plasma and blood using a high-performance liquid chromatograph-tandem mass spectrometer system. Non-compartmental analysis was used to derive pharmacokinetic parameters including the bioavailability. The Solutol formulation yielded better bioavailability reaching a maximum of about 14.6 and 7.3% in dogs and monkeys, respectively, following nominal oral dose of ca. 90 mg SR13668/m(2). Blood levels of SR13668 were consistently about threefold higher than those in plasma in both species. SR13668 did not cause untoward hematology, clinical chemistry, or coagulation effects in dogs or monkeys with the exception of a modest, reversible increase in liver function enzymes in monkeys. The lipid-based surfactant/emulsifiers, especially Solutol, markedly enhanced the oral bioavailability of SR13668 over that previously seen in preclinical studies. These formulations are being evaluated in a Phase 0 clinical study prior to further clinical development of this drug.

  5. Integrase of Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Snášel, Jan; Krejčík, Zdeněk; Jenčová, Věra; Rosenberg, Ivan; Ruml, Tomáš; Alexandratos, J.; Gustchina, A.; Pichová, Iva

    2005-01-01

    Roč. 272, č. 1 (2005), s. 203-216 ISSN 1742-464X R&D Projects: GA AV ČR(CZ) IAA4055304 Institutional research plan: CEZ:AV0Z4055905 Keywords : integrase * Mason-Pfizer monkey virus * HIV-1 Subject RIV: CE - Biochemistry

  6. Early Stages of Melody Processing: Stimulus-Sequence and Task-Dependent Neuronal Activity in Monkey Auditory Cortical Fields A1 and R

    Science.gov (United States)

    Yin, Pingbo; Mishkin, Mortimer; Sutter, Mitchell; Fritz, Jonathan B.

    2008-01-01

    To explore the effects of acoustic and behavioral context on neuronal responses in the core of auditory cortex (fields A1 and R), two monkeys were trained on a go/no-go discrimination task in which they learned to respond selectively to a four-note target (S+) melody and withhold response to a variety of other nontarget (S−) sounds. We analyzed evoked activity from 683 units in A1/R of the trained monkeys during task performance and from 125 units in A1/R of two naive monkeys. We characterized two broad classes of neural activity that were modulated by task performance. Class I consisted of tone-sequence–sensitive enhancement and suppression responses. Enhanced or suppressed responses to specific tonal components of the S+ melody were frequently observed in trained monkeys, but enhanced responses were rarely seen in naive monkeys. Both facilitatory and suppressive responses in the trained monkeys showed a temporal pattern different from that observed in naive monkeys. Class II consisted of nonacoustic activity, characterized by a task-related component that correlated with bar release, the behavioral response leading to reward. We observed a significantly higher percentage of both Class I and Class II neurons in field R than in A1. Class I responses may help encode a long-term representation of the behaviorally salient target melody. Class II activity may reflect a variety of nonacoustic influences, such as attention, reward expectancy, somatosensory inputs, and/or motor set and may help link auditory perception and behavioral response. Both types of neuronal activity are likely to contribute to the performance of the auditory task. PMID:18842950

  7. Analysis of the Cross-Reactivity of Various 56 kDa Recombinant Protein Antigens with Serum Samples Collected after Orientia tsutsugamushi Infection by ELISA

    Science.gov (United States)

    2011-01-01

    the cynomolgus monkey model. 37 This vaccine candidate has recently been evaluated for protection against heterolo- gous challenge with five non-Karp...72: 458 – 464 . 34. Kaminski RW , Turbyfill KR , Chao CC , Ching WM , Oaks EV , 2009 . Mucosal Adjuvanticity of a Shigella Invasin...vaccine candidate Kp r56 induces humoral and cellular immune responses in cyno- molgus monkeys . Infect Immun 73: 5039 – 5047 . 38. Shirai A

  8. Tonal frequency affects amplitude but not topography of rhesus monkey cranial EEG components.

    Science.gov (United States)

    Teichert, Tobias

    2016-06-01

    The rhesus monkey is an important model of human auditory function in general and auditory deficits in neuro-psychiatric diseases such as schizophrenia in particular. Several rhesus monkey studies have described homologs of clinically relevant auditory evoked potentials such as pitch-based mismatch negativity, a fronto-central negativity that can be observed when a series of regularly repeating sounds is disrupted by a sound of different tonal frequency. As a result it is well known how differences of tonal frequency are represented in rhesus monkey EEG. However, to date there is no study that systematically quantified how absolute tonal frequency itself is represented. In particular, it is not known if frequency affects rhesus monkey EEG component amplitude and topography in the same way as previously shown for humans. A better understanding of the effect of frequency may strengthen inter-species homology and will provide a more solid foundation on which to build the interpretation of frequency MMN in the rhesus monkey. Using arrays of up to 32 cranial EEG electrodes in 4 rhesus macaques we identified 8 distinct auditory evoked components including the N85, a fronto-central negativity that is the presumed homolog of the human N1. In line with human data, the amplitudes of most components including the N85 peaked around 1000 Hz and were strongly attenuated above ∼1750 Hz. Component topography, however, remained largely unaffected by frequency. This latter finding may be consistent with the known absence of certain anatomical structures in the rhesus monkey that are believed to cause the changes in topography in the human by inducing a rotation of generator orientation as a function of tonal frequency. Overall, the findings are consistent with the assumption of a homolog representation of tonal frequency in human and rhesus monkey EEG. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Diet Versus Phylogeny: a Comparison of Gut Microbiota in Captive Colobine Monkey Species.

    Science.gov (United States)

    Hale, Vanessa L; Tan, Chia L; Niu, Kefeng; Yang, Yeqin; Knight, Rob; Zhang, Qikun; Cui, Duoying; Amato, Katherine R

    2018-02-01

    Both diet and host phylogeny shape the gut microbial community, and separating out the effects of these variables can be challenging. In this study, high-throughput sequencing was used to evaluate the impact of diet and phylogeny on the gut microbiota of nine colobine monkey species (N = 64 individuals). Colobines are leaf-eating monkeys that fare poorly in captivity-often exhibiting gastrointestinal (GI) problems. This study included eight Asian colobines (Rhinopithecus brelichi, Rhinopithecus roxellana, Rhinopithecus bieti, Pygathrix nemaeus, Nasalis larvatus, Trachypithecus francoisi, Trachypithecus auratus, and Trachypithecus vetulus) and one African colobine (Colobus guereza). Monkeys were housed at five different captive institutes: Panxi Wildlife Rescue Center (Guizhou, China), Beijing Zoo, Beijing Zoo Breeding Center, Singapore Zoo, and Singapore Zoo Primate Conservation Breeding Center. Captive diets varied widely between institutions, but within an institution, all colobine monkey species were fed nearly identical or identical diets. In addition, four monkey species were present at multiple captive institutes. This allowed us to parse the effects of diet and phylogeny in these captive colobines. Gut microbial communities clustered weakly by host species and strongly by diet, and overall, colobine phylogenetic relationships were not reflected in gut microbiota analyses. Core microbiota analyses also identified several key taxa-including microbes within the Ruminococcaceae and Lachnospiraceae families-that were shared by over 90% of the monkeys in this study. Microbial species within these families include many butyrate producers that are important for GI health. These results highlight the importance of diet in captive colobines.

  10. Full-length cDNA sequences from Rhesus monkey placenta tissue: analysis and utility for comparative mapping

    Directory of Open Access Journals (Sweden)

    Lee Sang-Rae

    2010-07-01

    Full Text Available Abstract Background Rhesus monkeys (Macaca mulatta are widely-used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as cynomolgus monkeys (Macaca fascicularis, and to humans, sharing a last common ancestor from about 25 million years ago. Although rhesus monkeys have been studied extensively under field and laboratory conditions, research has been limited by the lack of genetic resources. The present study generated placenta full-length cDNA libraries, characterized the resulting expressed sequence tags, and described their utility for comparative mapping with human RefSeq mRNA transcripts. Results From rhesus monkey placenta full-length cDNA libraries, 2000 full-length cDNA sequences were determined and 1835 rhesus placenta cDNA sequences longer than 100 bp were collected. These sequences were annotated based on homology to human genes. Homology search against human RefSeq mRNAs revealed that our collection included the sequences of 1462 putative rhesus monkey genes. Moreover, we identified 207 genes containing exon alterations in the coding region and the untranslated region of rhesus monkey transcripts, despite the highly conserved structure of the coding regions. Approximately 10% (187 of all full-length cDNA sequences did not represent any public human RefSeq mRNAs. Intriguingly, two rhesus monkey specific exons derived from the transposable elements of AluYRa2 (SINE family and MER11B (LTR family were also identified. Conclusion The 1835 rhesus monkey placenta full-length cDNA sequences described here could expand genomic resources and information of rhesus monkeys. This increased genomic information will greatly contribute to the development of evolutionary biology and biomedical research.

  11. Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

    Science.gov (United States)

    Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

    2017-01-01

    Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity

  12. Daphnia magna shows reduced infection upon secondary exposure to a pathogen.

    Science.gov (United States)

    McTaggart, Seanna J; Wilson, Philip J; Little, Tom J

    2012-12-23

    Previous pathogen exposure is an important predictor of the probability of becoming infected. This is deeply understood for vertebrate hosts, and increasingly so for invertebrate hosts. Here, we test if an initial pathogen exposure changes the infection outcome to a secondary pathogen exposure in the natural host-pathogen system Daphnia magna and Pasteuria ramosa. Hosts were initially exposed to an infective pathogen strain, a non-infective pathogen strain or a control. The same hosts underwent a second exposure, this time to an infective pathogen strain, either immediately after the initial encounter or 48 h later. We observed that an initial encounter with a pathogen always conferred protection against infection compared with controls.

  13. Evaluation of the Differences of Myocardial Fibers between Acute and Chronic Myocardial Infarction: Application of Diffusion Tensor Magnetic Resonance Imaging in a Rhesus Monkey Model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuqing [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190 (China); Cai, Wei [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Department of Radiology, Beijing Jishuitan Hospital, 4th Clinical Medical College of Peking University, Beijing 100035 (China); Wang, Lei [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Xia, Rui [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China); Chen, Wei [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China); Department of Radiology, The First Affiliated Hospital of Kunming Medical University, Yunnan 650032 (China); Zheng, Jie [Mallinckrodt Institute of Radiology, School of Medicine, Washington University, St. Louis, MO 63110 (United States); Gao, Fabao [Department of Radiology, West China Hospital, Sichuan University, Sichuan 610041 (China)

    2016-11-01

    To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI. Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10{sup -4} mm{sup 2}/s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10{sup -4}mm{sup 2}/s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°–11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°–53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°–66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°–64.9 ± 4.3°). Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models.

  14. Psychophysical chromatic mechanisms in macaque monkey.

    Science.gov (United States)

    Stoughton, Cleo M; Lafer-Sousa, Rosa; Gagin, Galina; Conway, Bevil R

    2012-10-24

    Chromatic mechanisms have been studied extensively with psychophysical techniques in humans, but the number and nature of the mechanisms are still controversial. Appeals to monkey neurophysiology are often used to sort out the competing claims and to test hypotheses arising from the experiments in humans, but psychophysical chromatic mechanisms have never been assessed in monkeys. Here we address this issue by measuring color-detection thresholds in monkeys before and after chromatic adaptation, employing a standard approach used to determine chromatic mechanisms in humans. We conducted separate experiments using adaptation configured as either flickering full-field colors or heterochromatic gratings. Full-field colors would favor activity within the visual system at or before the arrival of retinal signals to V1, before the spatial transformation of color signals by the cortex. Conversely, gratings would favor activity within the cortex where neurons are often sensitive to spatial chromatic structure. Detection thresholds were selectively elevated for the colors of full-field adaptation when it modulated along either of the two cardinal chromatic axes that define cone-opponent color space [L vs M or S vs (L + M)], providing evidence for two privileged cardinal chromatic mechanisms implemented early in the visual-processing hierarchy. Adaptation with gratings produced elevated thresholds for colors of the adaptation regardless of its chromatic makeup, suggesting a cortical representation comprised of multiple higher-order mechanisms each selective for a different direction in color space. The results suggest that color is represented by two cardinal channels early in the processing hierarchy and many chromatic channels in brain regions closer to perceptual readout.

  15. Metabolite analysis of [11C]Ro15-4513 in mice, rats, monkeys and humans

    International Nuclear Information System (INIS)

    Kida, T.; Noguchi, J.; Zhang, M.-R.; Suhara, T.; Suzuki, K.

    2003-01-01

    We performed in vitro and in vivo assays of the metabolism of [ 11 C]Ro15-4513 over time in the plasma of mice, rats, monkeys and humans, using a radio-HPLC equipped with a sensitive positron detector, in order to compare the metabolic rates of the radiopharmaceutical agent among the different animal species and to establish a highly sensitive analytical method for the radiotracer agent. We also examined the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats. The analytical method used in this study permitted detection of even extremely low levels of radioactivity (approximately 5,000 dpm). In vitro experiments revealed that [ 11 C]Ro15-4513 in the blood was metabolized to hydrolysate [ 11 C]A. The species were classified in descending order of the metabolic rate of the radiotracer in vitro as follows; mice, rats, and monkeys/humans. In the in vitro experiment, the percentage of the unchanged drug in the plasma at 60 minutes postdose was 9% in mice, 70% in rats, 97% in monkeys, and 98% in humans. In vivo metabolite analysis in the blood showed the presence of two radioactive metabolites, consisting of one hydrolysate [ 11 C]A and another unidentified substance. The species were classified in descending order of the metabolic rate of the radiotracer in vivo as follows; mice, rats/humans, and monkeys. The percentage of the unchanged drug in the plasma was 6% in mice, 21% in rats, 26% in humans, and 40% in monkeys. Furthermore, the in vitro and in vivo experiments conducted to analyze the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats revealed that the radiotracer was metabolized to some extent in the brain tissue of these animals. In the in vivo experiment, the percentage of the unchanged drug at 60 min postdose was 86% in the brain tissue of mice and 88% in the brain tissue of rats, while in the in vitro experiment, the corresponding percentage was 93% in mice, and 91% in rats

  16. The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)

    Science.gov (United States)

    Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

    2010-01-01

    The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia. PMID:20227397

  17. Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys

    Science.gov (United States)

    Saletti, Patricia G.; Maior, Rafael S.; Hori, Etsuro; Nishijo, Hisao; Tomaz, Carlos

    2015-01-01

    Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys’ PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction. PMID:26441660

  18. Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

    International Nuclear Information System (INIS)

    Vasin, Mikhail V.; Antipov, Vsevolod V.; Ushakov, Igor B.; Semenov, Leonid F.; Lapin, Boris A.; Suvorov, Nikolai N.; Ilyin, Leonid A.

    2014-01-01

    The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2-3-years-old and weighing 2.1-3.5 kg were used. Animals were exposed to total-body gamma irradiation from 60 Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40-120 mg kg -1 ) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg -1 protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3-94.3) mg kg -1 , and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg -1 . Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys. (author)

  19. Molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees.

    Directory of Open Access Journals (Sweden)

    Weimin Liu

    2008-07-01

    Full Text Available Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2 and Ebola virus. Simian foamy viruses (SFVs are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724 were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706 or viral nucleic acids (n = 392. SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz; however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp, pol-RT (717 bp, and pol-IN (425 bp sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey

  20. A neural substrate for object permanence in monkey inferotemporal cortex

    OpenAIRE

    Puneeth, NC; Arun, SP

    2016-01-01

    We take it for granted that objects continue to exist after being occluded. This knowledge ? known as object permanence ? is present even in childhood, but its neural basis is not fully understood. Here, we show that monkey inferior temporal (IT) neurons carry potential signals of object permanence even in animals that received no explicit behavioral training. We compared two conditions with identical visual stimulation: the same object emerged from behind an occluder as expected following it...

  1. Activity of Two Chlorinated Lincomycin Analogues Against Chloroquine-Resistant Falciparum Malaria in Owl Monkeys1

    Science.gov (United States)

    Powers, Kendall G.; Jacobs, Richard L.

    1972-01-01

    The chloroquine-resistant Oak Knoll strain of Plasmodium falciparum, recently adapted to the owl monkey (Aotus trivirgatus), was insusceptible to chloroquine therapy. Two chlorinated lincomycin analogues tested in this host-parasite system cured blood-induced infections. Acute infections were treated orally for 7 consecutive days with either 15 or 75 mg of clindamycin hydrochloride (U-21) per kg per day, 10 or 50 mg of N-demethyl-4′-pentyl clindamycin hydrochloride (U-24) per kg per day, or 20 mg of chloroquine base per kg per day. These lincomycin analogues cleared trophozoites from the peripheral blood by the end of the 7-day treatment period. The speed of clearance of parasites was not dose-related, but curative activity appeared dependent upon the amount of drug given as well as the number of daily treatments. The efficacy of U-21 and U-24 is of particular interest since they represent major structural departures from compounds commonly used in the treatment of malaria. PMID:4207758

  2. The Monkey Puzzle: A Systematic Review of Studies of Stress, Social Hierarchies, and Heart Disease in Monkeys

    Science.gov (United States)

    Petticrew, Mark; Davey Smith, George

    2012-01-01

    Background It is often suggested that psychosocial factors, such as stress, or one's social position, may play an important role in producing social gradients in human disease. Evidence in favour of this model of health inequalities has relied, in part, on studies of the health effects of the natural social hierarchies found among non-human primates. This study aimed to assess the strength of this evidence. Methodology/Principal Findings A systematic review was carried out to identify all studies of psychosocial factors and coronary artery disease (CAD) in non-human primates. We searched databases (MEDLINE, PsycInfo, EMBASE, and Primatelit from inception to November 2010) to identify experimental and observational studies of the impact of social reorganisation, social instability, and disruption of dominance hierarchies on primate CAD outcomes. We also handsearched bibliographies and examined the citations to those studies in public health articles. Fourteen studies were found which presented evidence on CAD and social status and/or psychosocial stress. These suggested that the association between social status and disease may be sex-specific: in female monkeys dominant status may be protective, with subordinate females having a greater extent of atherosclerosis. In male monkeys the reverse may be the case. Conclusions/Significance Overall, non-human primate studies present only limited evidence for an association between social status and CAD, Despite this, there is selective citation of individual non-human primate studies in reviews and commentaries relating to human disease aetiology. Such generalisation of data from monkey studies to human societies does not appear warranted. PMID:22470414

  3. Monkeys Wait to Begin a Computer Task when Waiting Makes Their Responses More Effective

    Directory of Open Access Journals (Sweden)

    Theodore A. Evans

    2014-02-01

    Full Text Available Rhesus monkeys (Macaca mulatta and capuchin monkeys (Cebus apella performed a computerized inhibitory control task modeled after an “escalating interest task” from a recent human study (Young, Webb, & Jacobs, 2011. In the original study, which utilized a first-person shooter game, human participants learned to inhibit firing their simulated weapon long enough for the weapon‟s damage potential to grow in effectiveness (up to 10 seconds in duration. In the present study, monkeys earned food pellets for eliminating arrays of target objects using a digital eraser. We assessed whether monkeys could suppress trial-initiating joystick movements long enough for the eraser to grow in size and speed, thereby making their eventual responses more effective. Monkeys of both species learned to inhibit moving the eraser for as long as 10 seconds, and they allowed the eraser to grow larger for successively larger target arrays. This study demonstrates an interesting parallel in behavioral inhibition between human and nonhuman participants and provides a method for future comparative testing of human and nonhuman test groups.

  4. Radioprotective effectiveness of adeturone in monkey experiments

    International Nuclear Information System (INIS)

    Nikolov, I.; Pantev, T.; Rogozkin, P.; Chertkov, K.; Dikovenko, E.; Kosarenkov, V.

    1976-01-01

    The radioprotective effect of adeturone (adenosine triphsophate salt of AET) was tested on 28 monkeys (Macaca mulata). The animals were gamma-irradiated (cobalt 60) with a dose of 680 R (17,6 R/min, LDsub(100/18)). Adeturone was administered intravenously for 5 minutes, from 6 to 15 minutes before irradiation in a dose of 150 mg/kg (1/2 of thr maximal tolerable dose). It was found that adeturone administration before the absolute lethal irradiation will ensure survival of 50 % of the monkeys. Radiation sickness in protected animals runs a milder course as shown by the duration of the latency period, the manifestation of the hemorrhagic syndrome, the leukopenia and erythrocytes in the peripheral blood. Some symptoms do not appear at all (diarrhoea) or develop later(hyperthermia, hypodynamia). (A.B.)

  5. [Role of infection in the pathogenesis of obesity].

    Science.gov (United States)

    Hainer, Vojtěch; Hainerová, Irena Aldhoon; Zamrazilová, Hana

    2012-01-01

    Current global epidemic of obesity is mainly related to increased consumption of high energy density foods and sedentary lifestyle that leads to a positive energy balance with subsequent accumulation of fat stores, primarily in genetically predisposed individuals. However, additional pathogenetic factors should be considered, including an infection. Several viruses causing obesity have been described in mice, chicken, rats, hamsters and monkeys. In humans, a significant positive association between being overweight and IgG antibodies was found for Helicobacter pylori and Chlamydia pneumoniae. This association of bacterial infections with increased BMI might not represent a causal relationship but could be a marker for greater susceptibility of obese individuals to infection. Crucial role in the development of "infectious obesity" in humans may be played by adenovirus infection, particularly AD-36 type that is also capable of inducing obesity in experimental animals as chicken, mice and monkeys. AD-36-induced obesity is paradoxically associated with lower levels of serum cholesterol and triglycerides both in humans and in experimental animals. Moreover, AD-36 enhances insulin sensitivity and improves hepatic steatosis. AD-36 effects in target organs as adipose tissue, liver and skeletal muscle are mediated through the viral protein E4orf1. This way AD-36 improves metabolic profile, as indicated by a greater glucose uptake by adipose tissue and skeletal muscle, reduced glucose output by hepatocytes, increased adiponectin levels and increased expression of adipogenic genes as peroxisome proliferator-activated receptor gamma. If E4orf1 improves glycemic control without reducing dietary fat intake and body fat stores, this viral protein would be highly valuable to develop novel anti-diabetic agents that mimic its effects.Key words: obesity, infection, adenovirus AD-36, diabetes mellitus, lipid profile, insulin sensitivity.

  6. Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.

    Directory of Open Access Journals (Sweden)

    George Jiang

    Full Text Available Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA, alphavirus replicons (VRP, attenuated adenovirus serotype 5 (Ad, or attenuated poxvirus (Pox. These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost.

  7. Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey Cytochrome P450 2C9, a New Efavirenz Oxidase.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-07-01

    Cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. In humans, the cytochrome P450 (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, S-mephenytoin, and diclofenac. However, comprehensive evaluation regarding substrate specificity of monkey CYP2C9 has not been conducted. In the present study, 89 commercially available drugs were examined to find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled those of human CYP2C9 or CYP2C19, with some differences in substrate specificities. Although efavirenz is known as a marker substrate for human CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14 positions. These results suggest that the efavirenz 8-oxidation could be one of the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to limited specific differences in drug oxidative metabolism between cynomolgus monkeys and humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Risky business: rhesus monkeys exhibit persistent preferences for risky options.

    Science.gov (United States)

    Xu, Eric R; Kralik, Jerald D

    2014-01-01

    Rhesus monkeys have been shown to prefer risky over safe options in experiential decision-making tasks. These findings might be due, however, to specific contextual factors, such as small amounts of fluid reward and minimal costs for risk-taking. To better understand the factors affecting decision-making under risk in rhesus monkeys, we tested multiple factors designed to increase the stakes including larger reward amounts, distinct food items rather than fluid reward, a smaller number of trials per session, and risky options with greater variation that also included non-rewarded outcomes. We found a consistent preference for risky options, except when the expected value of the safe option was greater than the risky option. Thus, with equivalent mean utilities between the safe and risky options, rhesus monkeys appear to have a robust preference for the risky options in a broad range of circumstances, akin to the preferences found in human children and some adults in similar tasks. One account for this result is that monkeys make their choices based on the salience of the largest payoff, without integrating likelihood and value across trials. A related idea is that they fail to override an impulsive tendency to select the option with the potential to obtain the highest possible outcome. Our results rule out strict versions of both accounts and contribute to an understanding of the diversity of risky decision-making among primates.

  9. Pharmacokinetic modeling: Prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans

    International Nuclear Information System (INIS)

    Fisher, Jeffrey W.; Twaddle, Nathan C.; Vanlandingham, Michelle; Doerge, Daniel R.

    2011-01-01

    A physiologically based pharmacokinetic (PBPK) model was developed for bisphenol A (BPA) in adult rhesus monkeys using intravenous (iv) and oral bolus doses of 100 μg d6-BPA/kg (). This calibrated PBPK adult monkey model for BPA was then evaluated against published monkey kinetic studies with BPA. Using two versions of the adult monkey model based on monkey BPA kinetic data from and , the aglycone BPA pharmacokinetics were simulated for human oral ingestion of 5 mg d16-BPA per person (Völkel et al., 2002). Völkel et al. were unable to detect the aglycone BPA in plasma, but were able to detect BPA metabolites. These human model predictions of the aglycone BPA in plasma were then compared to previously published PBPK model predictions obtained by simulating the Völkel et al. kinetic study. Our BPA human model, using two parameter sets reflecting two adult monkey studies, both predicted lower aglycone levels in human serum than the previous human BPA PBPK model predictions. BPA was metabolized at all ages of monkey (PND 5 to adult) by the gut wall and liver. However, the hepatic metabolism of BPA and systemic clearance of its phase II metabolites appear to be slower in younger monkeys than adults. The use of the current non-human primate BPA model parameters provides more confidence in predicting the aglycone BPA in serum levels in humans after oral ingestion of BPA. -- Highlights: ► A bisphenol A (BPA) PBPK model for the infant and adult monkey was constructed. ► The hepatic metabolic rate of BPA increased with age of the monkey. ► The systemic clearance rate of metabolites increased with age of the monkey. ► Gut wall metabolism of orally administered BPA was substantial across all ages of monkeys. ► Aglycone BPA plasma concentrations were predicted in humans orally given oral doses of deuterated BPA.

  10. Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-12-01

    Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Myotoxicity of Gemfibrozil in Cynomolgus Monkey Model and Its Relationship to Pharmacokinetic Properties

    Science.gov (United States)

    Liu, Aiming; Xie, Shuilin; Sun, He; Gonzalez, Frank J.; Wei, Xiaoxiong; Dai, Renke

    2008-01-01

    Fibrate drugs are PPARα agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reported associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPARα agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third period (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey #2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly they exhibited a much higher incidence of myotoxicity than that of human. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity. PMID:19150455

  12. Myotoxicity of gemfibrozil in Cynomolgus monkey model and its relationship to pharmacokinetic properties

    International Nuclear Information System (INIS)

    Liu Aiming; Xie Shuilin; Sun He; Gonzalez, Frank J.; Wei Xiaoxiong; Dai Renke

    2009-01-01

    Fibrate drugs are PPARα agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reportedly associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPARα agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third period (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey no. 2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly, they exhibited a much higher incidence of myotoxicity than that of humans. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity

  13. Myotoxicity of gemfibrozil in Cynomolgus monkey model and its relationship to pharmacokinetic properties

    Energy Technology Data Exchange (ETDEWEB)

    Aiming, Liu; Shuilin, Xie [Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663 (China); He, Sun [School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072 (China); Gonzalez, Frank J [National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Xiaoxiong, Wei [Medpace, Inc., Cincinnati, OH 45212 (United States); Dai Renke [Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663 (China)], E-mail: dai_renke@gibh.ac.cn

    2009-03-15

    Fibrate drugs are PPAR{alpha} agonists prescribed for the treatment of dyslipidemia. Severe myotoxicity has been reportedly associated with their use albeit at a low frequency, especially for gemfibrozil. Few studies have investigated the mechanism of fibrate-induced myotoxicity in vivo. Considering the apparent species-related differences in PPAR{alpha} agonist-induced hepatotoxicity, we studied the myotoxicity of gemfibrozil in a Cynomolgus monkey model and explored the relationship between myotoxicity and pharmacokinetics. Six Cynomolgus monkeys were dosed with gemfibrozil twice daily at 600 mg/kg/day for the first two periods (P1 and P2, 8 days and 9 days respectively) and 300 mg/kg/day for the third period (P3, 14 days). Creatine kinase and myoglobin were measured, together with hepatotoxicity and nephrotoxicity markers. Behavioral responses were recorded for indication of toxicity. Pharmacokinetics was carried out following the 16th dosage of P1 and 17th dosage of P2 when myotoxicity was identified. Multivariable data analysis was employed to explore the relationship between pharmacokinetic parameters and myotoxicity markers. Consequently, myotoxicity occurred in monkey no. 2 (M2) and M6 in P1, M3 and M4 in P2, M3 and M6 in P3. Data analysis showed T80-150 (sustained time above the given concentration) contributed for myotoxicity discriminance and correlated with myotoxicity risk. This study revealed Cynomolgus monkey may be a good animal model for myotoxicity evaluation with sensitivity, reproducibility and similarities to humans. More interestingly, they exhibited a much higher incidence of myotoxicity than that of humans. Sustained high drug concentration plays an important role for the occurrence of myotoxicity. This may suggest an influence of drug transport and metabolism on myotoxicity.

  14. Pathogenesis of Escherichia coli O157:H7 Strain 86-24 Following Oral Infection of BALB/c Mice with an Intact Commensal Flora

    Science.gov (United States)

    2010-01-01

    inocula of these organisms are also needed to achieve colonization and disease in monkeys [29] and rabbits [30]. Our data suggested that the predominate...SB. Escherichia coli 0157:H7 srrains associared wirh haemorrhagic colitis in rhe Unired Srares produce a Shigella dysenreriae 1 (SHIGA) like...611-20. (29) Kang G, Pulimood AB, Koshi R. Hull A, Acheson D. Rajan P. er al. A monkey model for enrerohemorrhagic Escherichia coli infection. j

  15. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

    Science.gov (United States)

    Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

    2016-01-01

    Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

  16. Bioassay of circulating luteinizing hormone in the rhesus monkey: comparison with radioimmunoassay during physiological changes

    International Nuclear Information System (INIS)

    Dufau, M.L.; Hodgen, G.D.; Goodman, A.L.; Catt, K.J.

    1977-01-01

    The concentration of biologically active LH in Rhesus monkey (Macaca mulatta) serum was measured by a highly sensitive bioassay based upon testosterone production by dispersed rat interstitial cells. The sensitivity of the in vitro bioassay was equal to or higher than that of radioimmunoassay, with detection limits of 0.1 mIU of human menopausal gonadotropin (hMG) or 10 ng of a Rhesus pituitary gonadotropin preparation (LER-1909-2). Parallel dose-response curves were obtained for hMG and Rhesus monkey pituitary gonadotropin. The method permits bioassay of LH in 20--100 μl of serum from adult male monkeys, and from female monkeys during the follicular and luteal phases of the menstrual cycle. Bioactive LH concentrations could be assayed in 0.25 to 5 μl of serum from mid-cycle, postmenopausal, and castrated female monkeys. Serum LH was undetectable in two hypophysectomized adult female monkeys and six intact immature animals, and was 13 +- 6 (SD) mIU/ml in adult male monkeys. In adult females, follicular phase LH levels ranged from 17 to 169 mIU/ml, with a mean of 76 +- 52 mIU/ml. The midcycle LH peak was 1738 +- 742 mIU/ml and the luteal phase values ranged from 6-47 mIU/ml, with a mean of 35 +- 5 mIU/ml. Serum LH concentrations ranged from 100 to 900 mIU/ml in two menopausal females, and from 590--1480 mIU/ml in castrated females. Treatment of castrated female monkeys with estrogen plus progesterone produced an initial two-fold rise in sepum LH within 3 days, followed by a gradual decline to one-fourth to one-tenth of the initial levels after 10 days of treatment. Serum LH was suppressed to undetectable levels during the third week, and remained so for the duration of the 60-day treatment period

  17. Monkey Feeding Assay for Testing Emetic Activity of Staphylococcal Enterotoxin.

    Science.gov (United States)

    Seo, Keun Seok

    2016-01-01

    Staphylococcal enterotoxins (SEs) are unique bacterial toxins that cause gastrointestinal toxicity as well as superantigenic activity. Since systemic administration of SEs induces superantigenic activity leading to toxic shock syndrome that may mimic enterotoxic activity of SEs such as vomiting and diarrhea, oral administration of SEs in the monkey feeding assay is considered as a standard method to evaluate emetic activity of SEs. This chapter summarizes and discusses practical considerations of the monkey feeding assay used in studies characterizing classical and newly identified SEs.

  18. Hemopoiesis in monkeys in the course of and after total chronic irradiation

    International Nuclear Information System (INIS)

    Dzhikikidze, Eh.E.; Kosichenko, L.P.; Kuksova, M.I.

    1992-01-01

    Morphological and cytogenetic changes in blood-formation system of 2 types of monkeys were studied following chronic prolonged irradiation with low daily doses and considerable integral radiation load. Peak decrease of total leukocyte number of 1 mkl in both groups of monkeys at the expense of neutrophils was observed at integral dose of 10.78 Gy and was caused by decrease of index of neutrophil maturation. Violations of hereditary structures of bone marrow cells and peripheric blood lymphocytes were stable. Structural chromosomal aberrations remained in monkeys of both groups up to natural animal death. Quantitative and qualitative violations were less pronounced in macaca rhesus than in hamadryas baboons. This fact revealed high radiosensitivity of the baboons

  19. Basic Math in Monkeys and College Students

    OpenAIRE

    Beran, Michael J

    2008-01-01

    Recent behavioral and neuroimaging studies with humans and monkeys provide compelling evidence of shared numerical capacities across species. Our understanding of the emergence of human mathematical competence is well-served by these kinds of comparative assessments.

  20. The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells

    International Nuclear Information System (INIS)

    O'Neill, Frank J.; Greenlee, John E.; Carney, Helen

    2003-01-01

    Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

  1. Lateralization for visual processes: eye preference in Campbell's monkeys (Cercopithecus c. campbelli).

    Science.gov (United States)

    Chapelain, Amandine S; Blois-Heulin, Catherine

    2009-01-01

    Brain lateralization has been the matter of extensive research over the last centuries, but it remains an unsolved issue. While hand preferences have been extensively studied, very few studies have investigated laterality of eye use in non-human primates. We examined eye preference in 14 Campbell's monkeys (Cercopithecus c. campbelli). We assessed eye preference to look at a seed placed inside a tube using monocular vision. Eye use was recorded for 100 independent and non-rewarded trials per individual. All of the 14 monkeys showed very strong preferences in the choice of the eye used to look inside the tube (mean preference: 97.6%). Eight subjects preferred the right eye and six subjects preferred the left eye. The results are discussed in light of previous data on eye preference in primates, and compared to data on hand preference from these subjects. Our findings would support the hypothesis for an early emergence of lateralization for perceptual processes compared to manual motor functions.

  2. Effect of acoustic similarity on short-term auditory memory in the monkey.

    Science.gov (United States)

    Scott, Brian H; Mishkin, Mortimer; Yin, Pingbo

    2013-04-01

    Recent evidence suggests that the monkey's short-term memory in audition depends on a passively retained sensory trace as opposed to a trace reactivated from long-term memory for use in working memory. Reliance on a passive sensory trace could render memory particularly susceptible to confusion between sounds that are similar in some acoustic dimension. If so, then in delayed matching-to-sample, the monkey's performance should be predicted by the similarity in the salient acoustic dimension between the sample and subsequent test stimulus, even at very short delays. To test this prediction and isolate the acoustic features relevant to short-term memory, we examined the pattern of errors made by two rhesus monkeys performing a serial, auditory delayed match-to-sample task with interstimulus intervals of 1 s. The analysis revealed that false-alarm errors did indeed result from similarity-based confusion between the sample and the subsequent nonmatch stimuli. Manipulation of the stimuli showed that removal of spectral cues was more disruptive to matching behavior than removal of temporal cues. In addition, the effect of acoustic similarity on false-alarm response was stronger at the first nonmatch stimulus than at the second one. This pattern of errors would be expected if the first nonmatch stimulus overwrote the sample's trace, and suggests that the passively retained trace is not only vulnerable to similarity-based confusion but is also highly susceptible to overwriting. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Brandt-Christensen, M; Andersen, M B; Fink-Jensen, A

    2006-01-01

    -amphetamine-induced behaviours in EPS sensitised Cebus apella monkeys. (-)-OSU6162 was administered subcutaneously in doses of 1, 3, 6 and 9 mg/kg alone and in combination with (-)-apomorphine (0.25 mg/kg) or d-amphetamine (0.5 mg/kg). (-)-OSU6162 inhibited (-)-apomorphine-(1-9 mg/kg) as well as d-amphetamine (3-9 mg....../kg)-induced arousal and stereotypy. EPS did not occur when (-)-OSU6162 was administered in combination with (-)-apomorphine or d-amphetamine. However, when (-)-OSU6162 was administered alone, dystonia was observed at high doses (6 and 9 mg/kg) in two out of six monkeys. The present study shows that (-)-OSU6162 can...

  4. Experimental allergic encephalomyelitis in rhesus monkeys: MR spectroscopy comparison with histopathology and ultrastructure

    International Nuclear Information System (INIS)

    Cao Qian; Wang Lianqing; Wu Jing; Zhao Huadong; Zhai Jinping; Guo Xue; Liu Lianxiang; Wu Yujin

    2002-01-01

    Objective: To study the relationships between changes of rhesus monkeys with EAE in MRS and those in histopathology and ultrastructure. Methods: Nine rhesus monkeys were sensitized by the intradermal injection of homologous myelin basic protein or purified bovine MBP in complete Freund's adjuvant. The ratio of Cho/Cr and NAA/Cr was measured in EAE over course and compared with that before attack. Finally, the histologic characters of the disease was confirmed by light microscope and transmission electron microscope. Results: The lesions of acute and chronic form of EAE was extensive. The lesions of chronic form of EAE observed on MRI were multiple and limited, with mild inflammation. The ratios of NAA/Cr in acute and chronic form were decreased (t = 68.66, 5.69, separately, P < 0.05). A lot of vacuolation, hydropic degeneration, and lipofuscin in the axis-cylinders could be observed in both phases. The ratio of Cho/Cr in chronic EAE was increased (t = 3.48, P < 0.05). In acute form of EAE, severe inflammation, necrosis, and destruction of axons were observed in histopathology. However, chronic form of EAE showed marked demyelination. Conclusion: The ratios of Cho/Cr and NAA/Cr by MRS quantitative analysis can be used to determine different stages of the lesion and predict the histopathological feature in EAE in rhesus monkeys

  5. Face Pareidolia in the Rhesus Monkey.

    Science.gov (United States)

    Taubert, Jessica; Wardle, Susan G; Flessert, Molly; Leopold, David A; Ungerleider, Leslie G

    2017-08-21

    Face perception in humans and nonhuman primates is rapid and accurate [1-4]. In the human brain, a network of visual-processing regions is specialized for faces [5-7]. Although face processing is a priority of the primate visual system, face detection is not infallible. Face pareidolia is the compelling illusion of perceiving facial features on inanimate objects, such as the illusory face on the surface of the moon. Although face pareidolia is commonly experienced by humans, its presence in other species is unknown. Here we provide evidence for face pareidolia in a species known to possess a complex face-processing system [8-10]: the rhesus monkey (Macaca mulatta). In a visual preference task [11, 12], monkeys looked longer at photographs of objects that elicited face pareidolia in human observers than at photographs of similar objects that did not elicit illusory faces. Examination of eye movements revealed that monkeys fixated the illusory internal facial features in a pattern consistent with how they view photographs of faces [13]. Although the specialized response to faces observed in humans [1, 3, 5-7, 14] is often argued to be continuous across primates [4, 15], it was previously unclear whether face pareidolia arose from a uniquely human capacity. For example, pareidolia could be a product of the human aptitude for perceptual abstraction or result from frequent exposure to cartoons and illustrations that anthropomorphize inanimate objects. Instead, our results indicate that the perception of illusory facial features on inanimate objects is driven by a broadly tuned face-detection mechanism that we share with other species. Published by Elsevier Ltd.

  6. Neurotoxic response of infant monkeys to methylmercury

    Energy Technology Data Exchange (ETDEWEB)

    Willes, R.F.; Truelove, J.F.; Nera, E.A.

    1978-02-01

    Four infant monkeys were dosed orally with 500 ..mu..g Hg/kg body wt./day (as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28 to 29 days of treatment; the blood Hg levels were 8.0 to 9.4 ..mu..g Hg/g blood. Dosing was terminated at 28 to 29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35 to 43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver followed by occipital cortex and renal cortex. The mean blood/brain ratio was 0.21 +- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.

  7. Effect of Environmental Enrichment on Singly- and Group-Housed Squirrel Monkeys

    Science.gov (United States)

    Spring, Sarah E.; Clifford, James O.; Tomko, David L.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Nonhuman primates display an interest in novel places, habituate to new situations, and spend most of their daily activity in the wild in large groups engaging in feeding behaviors. Captivity changes these behaviors, and disrupts normal social hierarchies. In captivity, animals may exhibit stereotypical behaviors which are thought to indicate decreased psychological well-being (PWB). If an animal's behaviors can be made to approach those seen in the wild, and stereotypical behaviors are minimal it is assumed that PWB is adequate. Environmental enrichment (EE) devices have been used to address the Animal Welfare Act's requirement that the PWB of captive nonhuman primates be considered. The purpose of the present study was to examine whether various EE devices improve the PWB of captive squirrel monkeys. The present study used behavioral observation to quantify the effectiveness of several EE devices in reducing stereotypical behaviors in squirrel monkeys housed singly or in groups. Results showed that the EE devices used did not affect the expression of normal or stereotypical behaviors, but that the type of housing did.

  8. microRNA-128a dysregulation in transgenic Huntington’s disease monkeys

    Science.gov (United States)

    2014-01-01

    Background Huntington’s Disease (HD) is a progressive neurodegenerative disorder with a single causal mutation in the Huntingtin (HTT) gene. MicroRNAs (miRNAs) have recently been implicated as epigenetic regulators of neurological disorders, however, their role in HD pathogenesis is not well defined. Here we study transgenic HD monkeys (HD monkeys) to examine miRNA dysregulation in a primate model of the disease. Results In this report, 11 miRNAs were found to be significantly associated (P value monkeys. We further focused on one of those candidates, miR-128a, due to the corresponding disruption in humans and mice with HD as well as its intriguing lists of gene targets. miR-128a was downregulated in our HD monkey model by the time of birth. We then confirmed that miR-128a was also downregulated in the brains of pre-symptomatic and post-symptomatic HD patients. Additionally, our studies confirmed a panel of canonical HD signaling genes regulated by miR-128a, including HTT and Huntingtin Interaction Protein 1 (HIP1). Conclusion Our studies found that miR-128a may play a critical role in HD and could be a viable candidate as a therapeutic or biomarker of the disease. PMID:24929669

  9. The relationship between refractive and biometric changes during Edinger–Westphal stimulated accommodation in rhesus monkeys

    Science.gov (United States)

    Vilupuru, Abhiram S.; Glasser, Adrian

    2010-01-01

    Experiments were undertaken to understand the relationship between dynamic accommodative refractive and biometric (lens thickness (LT), anterior chamber depth (ACD) and anterior segment length (ASL=ACD+LT)) changes during Edinger–Westphal stimulated accommodation in rhesus monkeys. Experiments were conducted on three rhesus monkeys (aged 11·5, 4·75 and 4·75 years) which had undergone prior, bilateral, complete iridectomies and implantation of a stimulating electrode in the Edinger–Westphal (EW) nucleus. Accommodative refractive responses were first measured dynamically with video-based infrared photorefraction and then ocular biometric responses were measured dynamically with continuous ultrasound biometry (CUB) during EW stimulation. The same stimulus amplitudes were used for the refractive and biometric measurements to allow them to be compared. Main sequence relationships (ratio of peak velocity to amplitude) were calculated. Dynamic accommodative refractive changes are linearly correlated with the biometric changes and accommodative biometric changes in ACD, ASL and LT show systematic linear correlations with increasing accommodative amplitudes. The relationships are relatively similar for the eyes of the different monkeys. Dynamic analysis showed that main sequence relationships for both biometry and refraction are linear. Although accommodative refractive changes in the eye occur primarily due to changes in lens surface curvature, the refractive changes are well correlated with A-scan measured accommodative biometric changes. Accommodative changes in ACD, LT and ASL are all well correlated over the full extent of the accommodative response. PMID:15721617

  10. Autoshaping and automaintenance of a key-press response in squirrel monkeys.

    Science.gov (United States)

    Gamzu, E; Schwam, E

    1974-03-01

    Following exposure for a minimum of 500 to 600 trials, three of four naive squirrel monkeys eventually pressed a response key, illumination of which always preceded delivery of a food pellet. Three other naive monkeys did not press the key when the pellets were delivered randomly with respect to key illumination. Despite some similarities to autoshaping using pigeons, the data indicate many points of difference when squirrel monkeys are used as subjects. Although key-food pairings were shown to be important in the acquisition of the key-press response, they were ineffective in maintaining the response when either a negative response-reinforcer dependency was introduced, or when there was no scheduled response-reinforcer dependency (fixed trial). Not all demonstrations of autoshaping can be considered to be under the control of those processes that are primarily responsible for the phenomena obtained in pigeons.

  11. Enhanced mutagenesis of UV-irradiated simian virus 40 occurs in mitomycin C-treated host cells only at a low multiplicity of infection

    International Nuclear Information System (INIS)

    Sarasin, A.; Benoit, A.

    1986-01-01

    Treatment of monkey kidney cells with mitomycin C (MMC) 24 h prior to infection with UV-irradiated simian virus 40 (SV40) enhanced both virus survival and virus mutagenesis. The use of SV40 as a biological probe has been taken as an easy method to analyse SOS response of mammalian cells to the stress caused by DNA damage or inhibition of DNA replication. The mutation assay we used was based on the reversion from a temperature-sensitive phenotype (tsA58 mutant) to a wild-type phenotype. The optimal conditions for producing enhanced survival and mutagenesis in the virus progeny were determined with regard to the multiplicity of infection (MOI). Results showed that the level of enhanced mutagenesis observed for UV-irradiated virus grown in MMC-treated cells was an inverse function of the MOI, while enhanced survival was observed at nearly the same level regardless of the MOI. For the unirradiated virus, almost no increase in the mutation of virus progeny issued from MMC-treated cells was observed, while a small amount of enhanced virus survival was obtained. These results show that enhanced virus mutagenesis and enhanced virus survival can be dissociated under some experimental conditions. Enhanced virus mutagenesis, analogous to the error-prone replication of phages in SOS-induced bacteria, was observed, at least for SV40, only when DNA of both virus and host cells was damaged and when infection occurred with a small number of viral particles. We therefore hypothesize that an error-prone replication mode of UV-damaged templates is observed in induced monkey kidney cells

  12. Acute Zika Virus Infection in an Endemic Area Shows Modest Proinflammatory Systemic Immunoactivation and Cytokine-Symptom Associations

    Directory of Open Access Journals (Sweden)

    Jéssica Barletto de Sousa Barros

    2018-05-01

    Full Text Available An early immune response to Zika virus (ZIKV infection may determine its clinical manifestation and outcome, including neurological effects. However, low-grade and transient viremia limits the prompt diagnosis of acute ZIKV infection. We have investigated the plasma cytokine, chemokine, and growth factor profiles of 36 individuals from an endemic area displaying different symptoms such as exanthema, headache, myalgia, arthralgia, fever, hyperemia, swelling, itching, and nausea during early-phase infection. These profiles were then associated with symptoms, revealing important aspects of the immunopathophysiology of ZIKV infection. The levels of some cytokines/chemokines were significantly higher in acute ZIKV-infected individuals compared to healthy donors, including interferon (IFN gamma-induced protein 10 (IP-10, regulated on activation, normal T cell expressed and secreted (RANTES, IFN-γ, interleukin (IL-9, IL-7, IL-5, and IL-1ra, including some with predominantly immunoregulatory activity. Of note, we found that higher levels of IP-10 and IL-5 in ZIKV-infected individuals were strongly associated with exanthema and headache, respectively. Also, higher levels of IL-1ra were associated with subjects with arthralgia, whereas those with fever showed lower levels of granulocyte-colony stimulating factor (G-CSF. No correlation was observed between the number of symptoms and ZIKV viral load. Interestingly, only IP-10 showed significantly decreased levels in the recovery phase. In conclusion, our results indicate that acute ZIKV infection in a larger cohort resident to an endemic area displays a modest systemic immune activation profile, involving both proinflammatory and immunoregulatory cytokines and chemokines that could participate of virus control. In addition, we showed that differential cytokine/chemokine levels are related to specific clinical symptoms, suggesting their participation in underlying mechanisms.

  13. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    International Nuclear Information System (INIS)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo

    1996-01-01

    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

  14. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

  15. Polymorphic New World monkeys with more than three M/L cone types

    Science.gov (United States)

    Jacobs, Gerald H.; Deegan, Jess F.

    2005-10-01

    Most New World (platyrrhine) monkeys have M/L cone photopigment polymorphisms that map directly into individual variations in visual sensitivity and color vision. We used electroretinogram flicker photometry to examine M/L cone photopigments in the New World monkey Callicebus moloch (the dusky Titi). Like other New World monkeys, this species has an M/L cone photopigment polymorphism that reflects the presence of X-chromosome opsin gene alleles. However, unlike other platyrrhines in which three M/L photopigments are typical, Callicebus has a total of five M/L cone photopigments. The peak sensitivity values for these pigments extend across the range from 530 to 562 nm. The result is an enhanced array of potential color vision phenotypes in this species.

  16. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012

    International Nuclear Information System (INIS)

    Johnson, Reed F.; Bagci, Ulas; Keith, Lauren; Tang, Xianchun; Mollura, Daniel J.; Zeitlin, Larry; Qin, Jing; Huzella, Louis; Bartos, Christopher J.; Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H.; Paulty, Michael H.; Velasco, Jesus; Whaley, Kevin J.; Johnson, Joshua C.; Pettitt, James; Ork, Britini L.; Solomon, Jeffrey

    2016-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10"6 PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. - Highlights: • MERS-CoV Jordan-n3/2012 challenge of rhesus monkeys results in a mild disease. • CT can be used to monitor disease progression to aid models of human disease. • Treatment with the human monoclonal antibody 3B11-N resulted in decreased disease.

  17. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov [Emerging Viral Pathogens Section National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Bagci, Ulas [Center for Infectious Disease Imaging, National Institutes of Health Clinical Center, Bethesda MD 20892 (United States); Center for Research in Computer Vision (CRCV), Department of Electrics Electronics and Computer Science, University of Central Florida, Orlando, FL 32816, USA. (United States); Keith, Lauren [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Tang, Xianchun [Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215 (United States); Mollura, Daniel J. [Center for Infectious Disease Imaging, National Institutes of Health Clinical Center, Bethesda MD 20892 (United States); Zeitlin, Larry [Mapp Biopharmaceutical, Inc., San Diego CA 92121 (United States); Qin, Jing [Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Huzella, Louis; Bartos, Christopher J. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Bohorova, Natasha; Bohorov, Ognian; Goodman, Charles; Kim, Do H.; Paulty, Michael H.; Velasco, Jesus; Whaley, Kevin J. [Mapp Biopharmaceutical, Inc., San Diego CA 92121 (United States); Johnson, Joshua C.; Pettitt, James; Ork, Britini L. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States); Solomon, Jeffrey [Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research,Frederick, MD 21702-USA. (United States); and others

    2016-03-15

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10{sup 6} PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. - Highlights: • MERS-CoV Jordan-n3/2012 challenge of rhesus monkeys results in a mild disease. • CT can be used to monitor disease progression to aid models of human disease. • Treatment with the human monoclonal antibody 3B11-N resulted in decreased disease.

  18. Specific in vitro cleavage of Mason-Pfizer monkey virus capsid protein: evidence for a potential role of retroviral protease in early stages of infection

    International Nuclear Information System (INIS)

    Rumlova, Michaela; Ruml, Tomas; Pohl, Jan; Pichova, Iva

    2003-01-01

    Processing of Gag polyproteins by viral protease (PR) leads to reorganization of immature retroviral particles and formation of a ribonucleoprotein core. In some retroviruses, such as HIV and RSV, cleavage of a spacer peptide separating capsid and nucleocapsid proteins is essential for the core formation. We show here that no similar spacer peptide is present in the capsid-nucleocapsid (CA-NC) region of Mason-Pfizer monkey virus (M-PMV) and that the CA protein is cleaved in vitro by the PR within the major homology region (MHR) and the NC protein in several sites at the N-terminus. The CA cleavage product was also identified shortly after penetration of M-PMV into COS cells, suggesting that the protease-catalyzed cleavage is involved in core disintegration

  19. Metabolic alkalosis during immobilization in monkeys (M. nemestrina)

    Science.gov (United States)

    Young, D. R.; Yeh, I.; Swenson, R. S.

    1983-01-01

    The systemic and renal acid-base response of monkeys during ten weeks of immobilization was studied. By three weeks of immobilization, arterial pH and bicarbonate concentrations were elevated (chronic metabolic alkalosis). Net urinary acid excretion increased in immobilized animals. Urinary bicarbonate excretion decreased during the first three weeks of immobilization, and then returned to control levels. Sustained increases in urinary ammonium excretion were seen throughout the time duration of immobilization. Neither potassium depletion nor hypokalemia was observed. Most parameters returned promptly to the normal range during the first week of recovery. Factors tentatively associated with changes in acid-base status of monkeys include contraction of extracellular fluid volume, retention of bicarbonate, increased acid excretion, and possible participation of extrarenal buffers.

  20. Sensor placement on Canton Tower for health monitoring using asynchronous-climb monkey algorithm

    Science.gov (United States)

    Yi, Ting-Hua; Li, Hong-Nan; Zhang, Xu-Dong

    2012-12-01

    Heuristic optimization algorithms have become a popular choice for solving complex and intricate sensor placement problems which are difficult to solve by traditional methods. This paper proposes a novel and interesting methodology called the asynchronous-climb monkey algorithm (AMA) for the optimum design of sensor arrays for a structural health monitoring system. Different from the existing algorithms, the dual-structure coding method is designed and adopted for the representation of the design variables. The asynchronous-climb process is incorporated in the proposed AMA that can adjust the trajectory of each individual dynamically in the search space according to its own experience and other monkeys. The concept of ‘monkey king’ is introduced in the AMA, which reflects the Darwinian principle of natural selection and can create an interaction network to correctly guide the movement of other monkeys. Numerical experiments are carried out using two different objective functions by considering the Canton Tower in China with or without the antenna mast to evaluate the performance of the proposed algorithm. Investigations have indicated that the proposed AMA exhibits faster convergence characteristics and can generate sensor configurations superior in all instances when compared to the conventional monkey algorithm. For structures with stiffness mutation such as the Canton Tower, the sensor placement needs to be considered for each part separately.

  1. Sensor placement on Canton Tower for health monitoring using asynchronous-climb monkey algorithm

    International Nuclear Information System (INIS)

    Yi, Ting-Hua; Li, Hong-Nan; Zhang, Xu-Dong

    2012-01-01

    Heuristic optimization algorithms have become a popular choice for solving complex and intricate sensor placement problems which are difficult to solve by traditional methods. This paper proposes a novel and interesting methodology called the asynchronous-climb monkey algorithm (AMA) for the optimum design of sensor arrays for a structural health monitoring system. Different from the existing algorithms, the dual-structure coding method is designed and adopted for the representation of the design variables. The asynchronous-climb process is incorporated in the proposed AMA that can adjust the trajectory of each individual dynamically in the search space according to its own experience and other monkeys. The concept of ‘monkey king’ is introduced in the AMA, which reflects the Darwinian principle of natural selection and can create an interaction network to correctly guide the movement of other monkeys. Numerical experiments are carried out using two different objective functions by considering the Canton Tower in China with or without the antenna mast to evaluate the performance of the proposed algorithm. Investigations have indicated that the proposed AMA exhibits faster convergence characteristics and can generate sensor configurations superior in all instances when compared to the conventional monkey algorithm. For structures with stiffness mutation such as the Canton Tower, the sensor placement needs to be considered for each part separately. (paper)

  2. Prenatal methylmercury exposure affects spatial vision in adult monkeys

    International Nuclear Information System (INIS)

    Burbacher, Thomas M.; Grant, Kimberly S.; Mayfield, David B.; Gilbert, Steven G.; Rice, Deborah C.

    2005-01-01

    Decades of research have demonstrated that exposure to methylmercury (MeHg), a ubiquitous environmental pollutant, can have both early and long-term neurobehavioral consequences in exposed offspring. The present study assessed visual functioning in adult macaque monkeys (Macaca fascicularis) exposed in utero to 0, 50, 70, or 90 μg/kg/day of MeHg hydroxide. Twenty-one full-term, normal birth weight offspring (9 controls, 12 exposed) were tested at approximately 11-14.5 years of age on a visual contrast sensitivity task. A forced-choice tracking procedure was utilized with spatial frequencies of 1, 4, 10, and 20 cycles per degree of visual angle. On each test session, a single spatial frequency was presented across five levels of contrast, each differing by 3 dB. Methylmercury-exposed monkeys exhibited reduced contrast sensitivity thresholds, particularly at the higher spatial frequencies. The degree of visual impairment was not related to MeHg body burden or clearance and almost half of the exposed animals were unimpaired. The results from this study demonstrate that chronic in utero MeHg exposure, at subclinical levels, is associated with permanent adverse effects on spatial vision in adult monkeys

  3. Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Galler R.

    2005-01-01

    Full Text Available A chimeric yellow fever (YF-dengue serotype 2 (dengue 2 virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

  4. Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

    Science.gov (United States)

    Czoty, P W; Gould, R W; Gage, H D; Nader, M A

    2017-09-01

    Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [ 18 F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

  5. PET study of the distribution of [{sup 11}C]fluoxetine in a monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, C.-Y.; Shiue, Grace G.; Cornish, Kurtis G.; O' Rourke, Maria F

    1995-07-01

    No-carrier-added [{sup 11}C]fluoxetine (2) was synthesized by methylation of norfluoxetine (1) with [{sup 11}C]H{sub 3}I in 20% radiochemical yield in a synthesis time of 40 min from EOB with a specific activity of 0.48 Ci/{mu}M (EOB). In vivo study in mouse indicated that the uptake of 2 in mouse tissues was high and the radioactivity remained constant throughout the study. The uptake of 2 in mouse brain was 4%/g. PET study in a Rhesus monkey also showed that the uptakes of 2 in different brain regions were similar and the retention of radioactivity in these regions remained constant throughout the study (80 min). Analysis of arterial plasma by HPLC showed that only 20% of radioactivity in the plasma remained as 2 at 30 min post-injection. These results suggest that the uptake of fluoxetine in monkey brain is probably not receptor mediated. Rather, blood flow, lipophilicity or other transport mechanisms may play a role in its uptake.

  6. A specialized face-processing model inspired by the organization of monkey face patches explains several face-specific phenomena observed in humans.

    Science.gov (United States)

    Farzmahdi, Amirhossein; Rajaei, Karim; Ghodrati, Masoud; Ebrahimpour, Reza; Khaligh-Razavi, Seyed-Mahdi

    2016-04-26

    Converging reports indicate that face images are processed through specialized neural networks in the brain -i.e. face patches in monkeys and the fusiform face area (FFA) in humans. These studies were designed to find out how faces are processed in visual system compared to other objects. Yet, the underlying mechanism of face processing is not completely revealed. Here, we show that a hierarchical computational model, inspired by electrophysiological evidence on face processing in primates, is able to generate representational properties similar to those observed in monkey face patches (posterior, middle and anterior patches). Since the most important goal of sensory neuroscience is linking the neural responses with behavioral outputs, we test whether the proposed model, which is designed to account for neural responses in monkey face patches, is also able to predict well-documented behavioral face phenomena observed in humans. We show that the proposed model satisfies several cognitive face effects such as: composite face effect and the idea of canonical face views. Our model provides insights about the underlying computations that transfer visual information from posterior to anterior face patches.

  7. Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

    Science.gov (United States)

    Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

    2012-01-01

    Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

  8. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Directory of Open Access Journals (Sweden)

    Jennifer H Campbell

    2014-12-01

    Full Text Available Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab once a week for three weeks beginning on 28 days post-infection (late. Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS, and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+ in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  9. Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

    Science.gov (United States)

    Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

    2014-12-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

  10. Measurement of neuronal activity in a macaque monkey in response to animate images using near-infrared spectroscopy (NIRS

    Directory of Open Access Journals (Sweden)

    Masumi Wakita

    2010-06-01

    Full Text Available Near-infrared spectroscopy (NIRS has been used extensively for functional neuroimaging over the past decade, in part because it is considered a powerful tool for investigating brain function in human infants and young children, for whom other neuroimaging techniques are not suitable. In particular, several studies have measured hemodynamic responses in the occipital region in infants upon exposure to visual stimuli. In the present study, we used a multi-channel NIRS to measure neuronal activity in a macaque monkey who was trained to watch videos showing various circus animals performing acrobatic activities without fixing the head position of the monkey. Cortical activity from the occipital region was measured first by placing a probe comprising a 3x5 array of emitters and detectors (2 x 4 cm on the area (area 17, and the robustness and stability of the results were confirmed across sessions. Cortical responses were then measured from the dorsofrontal region. The oxygenated hemoglobin signals increased in area 9 and decreased in area 8b in response to viewing the videos. The results suggest that these regions are involved in cognitive processing of visually presented stimuli. The monkey showed positive responsiveness to the stimuli from the affective standpoint, but its attentional response to them was an inhibitory one.

  11. Processing of pro-opiomelanocortin-derived amidated joining peptide and glycine-extended precursor in monkey pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1991-01-01

    The molecular forms of proopiomelanocortin (POMC) derived amidated and C-terminal glycine-extended joining peptide from monkey (Macaca mulatta) pituitary were determined. The predominant forms of joining peptide found were the low molecular peptides POMC(76-105) and POMC(76-106), respectively...... sequence of monkey and human POMC extremely conserved, but also the processing patterns are similar. The monkey therefore serves as a suitable model for studying regulation of the processing of POMC and the hypothalamus-pituitary-adrenal axis in man....

  12. Behavioral thermoregulation in a group of zoo-housed colobus monkeys (Colobus guereza).

    Science.gov (United States)

    Wark, Jason D; Kuhar, Christopher W; Lukas, Kristen E

    2014-01-01

    Although wild primates are known to modify behavior in response to thermal stress, less is known about behavioral thermoregulation in zoo-housed primates. Zoo exhibits expose individuals to unique thermal environments and may constrain the thermoregulatory strategies available to individual animals. In this study, we observed a group of seven colobus monkeys (Colobus guereza) living on a concrete "Monkey Island" style exhibit that featured limited shade and limited arboreal space. Behaviors were recorded using continuous focal animal sampling (n = 63 days, 97.7 hr). Logistic regression revealed 23°C was the temperature at which monkeys began resting more in shade than in sun. When temperatures exceeded 23°C, animals spent more time in open sitting postures with limbs extended from the body; sat less frequently in closed, hunched postures; spent more time in social contact; and performed more self-directed behaviors. Exhibit use also shifted under higher temperatures, with more time spent in areas with shade and lower surface temperatures. Lastly, when provided with access to an indoor holding area, the colobus monkeys spent more than half the time indoors when temperatures exceeded 23°C, yet only 10% of their time indoors when the temperature was below this value. Although postural changes have been reported in wild colobus, the postural and other behavioral changes observed in the current study occurred at temperatures lower than expected based on the published thermoneutral zone of colobus monkeys and highlight the importance of considering the specific thermoregulatory responses of zoo animals. © 2014 Wiley Periodicals, Inc.

  13. Partial recovery of hemiparesis following hemispherectomy in infant monkeys.

    Science.gov (United States)

    Burke, Mark W; Zangenehpour, Shahin; Ptito, Maurice

    2010-01-22

    Hemiparesis, unilateral weakness or partial paralysis, is a common outcome following hemispherectomy in humans. We use the non-human primate as an invaluable translational model for our understanding of developmental plasticity in response to hemispherectomy. Three infant vervet monkeys (Chlorocebus sabeus) underwent hemispherectomy at a median age of 9 weeks and two additional monkeys at 48 months. Gross motor assessment was conducted in a large open field that contained a horizontal bar spanning the width of the cage. Subjects were assessed yearly following surgery in infantile lesions for a period of 3 years. Adult-lesioned subjects were assessed 40 months following surgery. Shortly after surgery both infant and adult-lesioned subjects were unable to move the contralateral side of their body, but all subjects were able to walk within 6 months following surgery. At each time point the lower limb gait was normal in infant-lesioned subjects with no apparent limp or dragging, however the upper limb demonstrated significant impairment. Horizontal bar crossing was significantly impaired during the first 24 months following surgery. Adult-lesioned subjects also displayed upper limb movement impairments similar to infant-lesioned subjects. In addition the adult-lesioned subjects displayed a noticeable lower limb limp, which was not observed in the infant-lesioned group. Both groups at each time point showed a propensity for ipsiversive turning. The upper limb gait impairment and horizontal bar crossing of lesioned subjects are reminiscent of hemiparesis seen in hemisperectomized humans with the young-lesioned subjects showing a greater propensity for recovery. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  14. Development of a high-throughput colorimetric Zika virus infection assay.

    Science.gov (United States)

    Müller, Janis A; Harms, Mirja; Schubert, Axel; Mayer, Benjamin; Jansen, Stephanie; Herbeuval, Jean-Philippe; Michel, Detlef; Mertens, Thomas; Vapalahti, Olli; Schmidt-Chanasit, Jonas; Münch, Jan

    2017-04-01

    Zika virus (ZIKV) is an emerging pathogen that causes congenital infections which may result in birth defects, such as microcephaly. Currently, no approved treatment or vaccination is available. ZIKV can be readily detected in cell culture where virally infected cells are normally stained by specific antibodies. As ZIKV regularly causes a cytopathic effect, we were wondering whether this viral property can be used to quantitatively determine viral infectivity. We here describe the use of an 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide-(MTT)-based cell viability assay that allows to determine ZIKV-induced cell death. We show that this colorimetric assay quantifies ZIKV infection over a broad range of viral dilutions in both monkey and human cells. It allows to determine inhibitory activities of antivirals that block ZIKV or to define the neutralizing antibody titers of ZIKV antisera. This MTT-based ZIKV detection assay can be evaluated by naked eye or computational tools, has a broad linear range, does not require large equipment or costly reagents, and thus represents a promising alternative to antibody-based assays, in particular in resource-poor settings. We propose to use this simple, fast, and cheap method for quantification of ZIKV neutralizing antibodies and testing of antiviral compounds.

  15. Nutritional and health status of woolly monkeys

    NARCIS (Netherlands)

    Ange-van Heugten, K.D.; Timmer, S.; Jansen, W.L.; Verstegen, M.W.A.

    2008-01-01

    Woolly monkeys (Lagothrix lagotricha and L. flavicauda) are threatened species in the wild and in captivity. Numerous zoological institutions have historically kept Lagothrix lagotricha spp., but only a few of them have succeeded in breeding populations. Therefore the majority of institutions that

  16. Soluble rhesus lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge.

    Directory of Open Access Journals (Sweden)

    Junji Sashihara

    2011-10-01

    Full Text Available Epstein-Barr virus (EBV is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350 or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]. No comparative trials, however, have been performed. Rhesus lymphocryptovirus (LCV encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated rhesus monkeys at 0, 4 and 12 weeks with (a soluble rhesus LCV gp350, (b virus-like replicon particles (VRPs expressing rhesus LCV gp350, (c VRPs expressing rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with rhesus LCV, animals vaccinated with soluble rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with

  17. HAVCR1 (CD365) and Its Mouse Ortholog Are Functional Hepatitis A Virus (HAV) Cellular Receptors That Mediate HAV Infection.

    Science.gov (United States)

    Costafreda, Maria Isabel; Kaplan, Gerardo

    2018-05-01

    The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), classified as CD365, was initially discovered as an HAV cellular receptor using an expression cloning strategy. Due to the lack of HAV receptor-negative replication-competent cells, it was not possible to fully prove that HAVCR1 was a functional HAV receptor. However, biochemistry, classical virology, and epidemiology studies further supported the functional role of HAVCR1 as an HAV receptor. Here, we show that an anti-HAVCR1 monoclonal antibody that protected African green monkey kidney (AGMK) cells against HAV infection only partially protected monkey Vero E6 cells and human hepatoma Huh7 cells, indicating that these two cell lines express alternative yet unidentified HAV receptors. Therefore, we focused our work on AGMK cells to further characterize the function of HAVCR1 as an HAV receptor. Advances in clustered regularly interspaced short palindromic repeat/Cas9 technology allowed us to knock out the monkey ortholog of HAVCR1 in AGMK cells. The resulting AGMK HAVCR1 knockout (KO) cells lost susceptibility to HAV infection, including HAV-free viral particles (vpHAV) and exosomes purified from HAV-infected cells (exo-HAV). Transfection of HAVCR1 cDNA into AGMK HAVCR1 KO cells restored susceptibility to vpHAV and exo-HAV infection. Furthermore, transfection of the mouse ortholog of HAVCR1, mHavcr1, also restored the susceptibility of AGMK HAVCR1 KO cells to HAV infection. Taken together, our data clearly show that HAVCR1 and mHavcr1 are functional HAV receptors that mediate HAV infection. This work paves the way for the identification of alternative HAV receptors to gain a complete understanding of their interplay with HAVCR1 in the cell entry and pathogenic processes of HAV. IMPORTANCE HAVCR1, an HAV receptor, is expressed in different cell types, including regulatory immune cells and antigen-presenting cells. How HAV evades the immune response during a long incubation period of up to 4 weeks and the

  18. The effect of environmental enrichment on the behavior of captive tufted capuchin monkeys (Cebus apella)

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten R; Mikkelsen, L F; Hau, J

    2010-01-01

    The authors provided different forms of environmental enrichment to six old laboratory male tufted capuchin monkeys (Cebus apella) and studied the behavior of the monkeys during a baseline period and during three enrichment periods. Each observation period lasted 5 d, with an interval of 6 d...... between periods. During the first enrichment period, the authors provided Buster cubes and wood cylinders with drilled holes filled with gum arabic. During the second enrichment period, monkeys were provided with a deep litter of bark shavings, and during the third enrichment period, they were given...... Buster cubes, wood cylinders and bark shavings. When provided with enrichment, the monkeys engaged in natural, species-specific activities and began to exhibit behavioral profiles that more closely resembled those of their natural counterparts. This suggests that their psychological well-being had...

  19. Noisy Spiking in Visual Area V2 of Amblyopic Monkeys.

    Science.gov (United States)

    Wang, Ye; Zhang, Bin; Tao, Xiaofeng; Wensveen, Janice M; Smith, Earl L; Chino, Yuzo M

    2017-01-25

    Interocular decorrelation of input signals in developing visual cortex can cause impaired binocular vision and amblyopia. Although increased intrinsic noise is thought to be responsible for a range of perceptual deficits in amblyopic humans, the neural basis for the elevated perceptual noise in amblyopic primates is not known. Here, we tested the idea that perceptual noise is linked to the neuronal spiking noise (variability) resulting from developmental alterations in cortical circuitry. To assess spiking noise, we analyzed the contrast-dependent dynamics of spike counts and spiking irregularity by calculating the square of the coefficient of variation in interspike intervals (CV 2 ) and the trial-to-trial fluctuations in spiking, or mean matched Fano factor (m-FF) in visual area V2 of monkeys reared with chronic monocular defocus. In amblyopic neurons, the contrast versus response functions and the spike count dynamics exhibited significant deviations from comparable data for normal monkeys. The CV 2 was pronounced in amblyopic neurons for high-contrast stimuli and the m-FF was abnormally high in amblyopic neurons for low-contrast gratings. The spike count, CV 2 , and m-FF of spontaneous activity were also elevated in amblyopic neurons. These contrast-dependent spiking irregularities were correlated with the level of binocular suppression in these V2 neurons and with the severity of perceptual loss for individual monkeys. Our results suggest that the developmental alterations in normalization mechanisms resulting from early binocular suppression can explain much of these contrast-dependent spiking abnormalities in V2 neurons and the perceptual performance of our amblyopic monkeys. Amblyopia is a common developmental vision disorder in humans. Despite the extensive animal studies on how amblyopia emerges, we know surprisingly little about the neural basis of amblyopia in humans and nonhuman primates. Although the vision of amblyopic humans is often described as

  20. Electrical stimulation of superior colliculus affects strabismus angle in monkey models for strabismus

    Science.gov (United States)

    Upadhyaya, Suraj; Meng, Hui

    2017-01-01

    Disruption of binocular vision during the critical period for development leads to eye misalignment in humans and in monkey models. We have previously suggested that disruption within a vergence circuit could be the neural basis for strabismus. Electrical stimulation in the rostral superior colliculus (rSC) leads to vergence eye movements in normal monkeys. Therefore, the purpose of this study was to investigate the effect of SC stimulation on eye misalignment in strabismic monkeys. Electrical stimulation was delivered to 51 sites in the intermediate and deep layers of the SC (400 Hz, 0.5-s duration, 10–40 μA) in 3 adult optical prism-reared strabismic monkeys. Scleral search coils were used to measure movements of both eyes during a fixation task. Staircase saccades with horizontal and vertical components were elicited by stimulation as predicted from the SC topographic map. Electrical stimulation also resulted in significant changes in horizontal strabismus angle, i.e., a shift toward exotropia/esotropia depending on stimulation site. Electrically evoked saccade vector amplitude in the two eyes was not significantly different (P > 0.05; paired t-test) but saccade direction differed. However, saccade disconjugacy accounted for only ~50% of the change in horizontal misalignment while disconjugate postsaccadic movements accounted for the other ~50% of the change in misalignment due to electrical stimulation. In summary, our data suggest that electrical stimulation of the SC of strabismic monkeys produces a change in horizontal eye alignment that is due to a combination of disconjugate saccadic eye movements and disconjugate postsaccadic movements. NEW & NOTEWORTHY Electrical stimulation of the superior colliculus in strabismic monkeys results in a change in eye misalignment. These data support the notion of developmental disruption of vergence circuits leading to maintenance of eye misalignment in strabismus. PMID:28031397

  1. Homogeneous antibodies in lethally irradiated and autologous bone marrow reconstituted Rhesus monkeys

    International Nuclear Information System (INIS)

    Berg, P. Van Den; Radl, J.; Loewenberg, B.; Swart, A.C.W.

    1976-01-01

    Ten Rhesus monkeys were lethally irradiated and reconstituted with autologous bone marrow. During the restoration period, the animals were immunized with DNP-Rhesus albumin and IgA1lambda-10S human paraprotein. One or more transient homogenous immunoglobulin components appeared in sera of all experimental monkeys. In four animals, these homogeneous immunoglobulins were shown to be specific antibodies against DNP-Rhesus albumin. They gradually became as heterogeneous as those in control monkeys which were immunized but not irradiated and transplanted. The onset of the specific antibody response after immunization was slightly delayed in the experimental group. On determining the time necessary to reach normalization of the overall immunoglobulin levels and the normal heterogeneity of the immunoglobulin spectrum, it was found to be more than 1 year in most of the animals. (author)

  2. Metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey.

    Science.gov (United States)

    Yu, Hong; Barrass, Nigel; Gales, Sonya; Lenz, Eva; Parry, Tony; Powell, Helen; Thurman, Dale; Hutchison, Michael; Wilson, Ian D; Bi, Luke; Qiao, Junwen; Qin, Qiuping; Ren, Jin

    2015-03-01

    1. Paracetamol overdose remains the leading cause of acute liver failure in humans. This study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. No adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. Only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals were observed, with no clear dose response. 3. Toxicokinetic analysis showed good plasma exposure, albeit with less than proportional rises in Cmax and AUC, with increasing dose. The Cmax values in monkey were up to 3.5 times those associated with human liver toxicity and the AUC approx. 1000 times those associated with liver enzyme changes in 31-44% of human subjects. 4. Metabolite profiling of urine by (1)H NMR spectroscopy revealed paracetamol and its glucuronide and sulphate metabolites. Glutathione-derived metabolites, e.g. the cysteinyl conjugate, were only present in very low concentrations whilst the mercapturate was not detected. 5. These in vivo observations demonstrated that the cynomolgus monkey is remarkably resistant to paracetamol-induced toxicity and a poor model for investigating paracetamol-related hepatotoxicity in humans.

  3. Multi circular-cavity surface coil for magnetic resonance imaging of monkey's brain at 4 Tesla

    Science.gov (United States)

    Osorio, A. I.; Solis-Najera, S. E.; Vázquez, F.; Wang, R. L.; Tomasi, D.; Rodriguez, A. O.

    2014-11-01

    Animal models in medical research has been used to study humans diseases for several decades. The use of different imaging techniques together with different animal models offers a great advantage due to the possibility to study some human pathologies without the necessity of chirurgical intervention. The employ of magnetic resonance imaging for the acquisition of anatomical and functional images is an excellent tool because its noninvasive nature. Dedicated coils to perform magnetic resonance imaging experiments are obligatory due to the improvement on the signal-to-noise ratio and reduced specific absorption ratio. A specifically designed surface coil for magnetic resonance imaging of monkey's brain is proposed based on the multi circular-slot coil. Numerical simulations of the magnetic and electric fields were also performed using the Finite Integration Method to solve Maxwell's equations for this particular coil design and, to study the behavior of various vector magnetic field configurations and specific absorption ratio. Monkey's brain images were then acquired with a research-dedicated magnetic resonance imaging system at 4T, to evaluate the anatomical images with conventional imaging sequences. This coil showed good quality images of a monkey's brain and full compatibility with standard pulse sequences implemented in research-dedicated imager.

  4. Neuromyelitis optica immunoglobulin G in Chinese patients detected by immunofluorescence assay on a monkey brain substrate.

    Science.gov (United States)

    Long, Youming; Hu, Xueqiang; Peng, Fuhua; Lu, Zhengqi; Wang, Yuge; Yang, Yu; Qiu, Wei

    2012-01-01

    Serum neuromyelitis optica immunoglobulin G (NMO-IgG) is used as a biomarker to differentiate between neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the original assay is expensive and complex and shows low sensitivity. Here, we investigated the potential of NMO-IgG detection using an indirect immunofluorescence (IIF) assay on monkey brains. NMO-IgG seroprevalence was determined in 168 samples by an IIF assay on a monkey brain substrate. The data were compared with those from a standard mouse brain IIF assay using McNemar and kappa tests. Thirty-one of 50 (62%) NMO patients, 7 of 18 (38.9%) longitudinally extensive transverse myelitis patients, 6 of 57 (10.5%) MS patients, and 5 of 10 (50%) optic neuritis patients were seropositive for NMO-IgG. None of the acute partial transverse myelitis patients (n = 3) or healthy controls (n = 20) was positive. Thus, the sensitivity of the test was 62% for the patients with clinically definite NMO. The specificity was 89.5%, considering the 57 MS patients as the control group. The modified IIF assay on monkey brains and the standard IIF assay based on mouse brains were not significantly different (McNemar test; p = 1.000). The two assays were concordant in 39 seropositive samples and 100 seronegative samples (kappa test; kappa = 0.592, p monkey brain assay was no better than the standard mouse brain IIF assay, we affirmed that NMO-IgG is a sensitive and specific biomarker to differentiate between NMO and MS. Copyright © 2011 S. Karger AG, Basel.

  5. Data of 10 SSR markers for genomes of homo sapiens and monkeys.

    Science.gov (United States)

    Reddy, K K V V V S; Raju, S Viswanadha; Someswara Rao, Chinta

    2017-06-01

    In this data, we present 10 Simple Sequence Repeat(SSR) markers TAGA, TCAT, GAAT, AGAT, AGAA, GATA, TATC, CTTT, TCTG and TCTA which are extracted from the genomes of homo sapiens and monkeys using string matching mechanism [1]. All loci showed 4 Base Pair(bp) in allele size, indicating that there are some polymorphisms between individuals correlating to the number of SSR repeats that maybe useful for the detection of similarity among the genotypes. Collectively, these data show that the SSR extraction is a valuable method to illustrate genetic variation of genomes.

  6. Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.

    Science.gov (United States)

    Cong, Yu; Lentz, Margaret R; Lara, Abigail; Alexander, Isis; Bartos, Christopher; Bohannon, J Kyle; Hammoud, Dima; Huzella, Louis; Jahrling, Peter B; Janosko, Krisztina; Jett, Catherine; Kollins, Erin; Lackemeyer, Matthew; Mollura, Daniel; Ragland, Dan; Rojas, Oscar; Solomon, Jeffrey; Xu, Ziyue; Munster, Vincent; Holbrook, Michael R

    2017-04-01

    Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.

  7. Pathobiological and Behavioral Effects of Lead Intoxication in the Infant Rhesus Monkey

    Science.gov (United States)

    Allen, J. R.; McWey, P. J.; Suomi, S. J.

    1974-01-01

    When infant rhesus monkeys were exposed to lead via the addition of lead acetate (0.5–9 mg/kg body weight) to their formula or by the consumption of lead particles from lead-based surrogate mothers, they developed symptoms of lead intoxication within 6 weeks. Seizures, muscular tremors, and altered social interaction were the predominant changes. Visual impairment was also apparent in the more severely affected animals. In the animals showing obvious symptoms lead levels varied between 300 to 500 μg/100 ml of blood. Even in those animals having blood lead levels below 100 μg, hyperactivity and insomnia were observed. When the exposure to lead was eliminated, seizures subsided and visual impairment was reduced; however, the abnormal social interaction persisted. These animals also experienced a gradual decline in hematocrit and hemoglobin values during the period of examination. Liver and kidney biopsies obtained from these lead-exposed animals revealed characteristic intranuclear inclusions. When adolescent and adult monkeys were exposed to doses of lead acetate similar to those employed in the infant experiments, lead levels in excess of 200 μg/100 ml of blood were recorded. However, there were no obvious behavioral abnormalities observed. There were, however, numerous lead inclusion bodies in kidney biopsy specimens from these animals. These data suggest that, like man, the infant nonhuman primate is much more susceptible to lead intoxication than is the adult. The clinical and behavioral changes recorded in these infant rhesus monkeys suggest their use as an experimental model to evaluate lead intoxication. ImagesFIGURE 6. PMID:4208658

  8. Old world monkeys compare to apes in the primate cognition test battery.

    Directory of Open Access Journals (Sweden)

    Vanessa Schmitt

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

  9. Distinct neural patterns enable grasp types decoding in monkey dorsal premotor cortex

    Science.gov (United States)

    Hao, Yaoyao; Zhang, Qiaosheng; Controzzi, Marco; Cipriani, Christian; Li, Yue; Li, Juncheng; Zhang, Shaomin; Wang, Yiwen; Chen, Weidong; Chiara Carrozza, Maria; Zheng, Xiaoxiang

    2014-12-01

    Objective. Recent studies have shown that dorsal premotor cortex (PMd), a cortical area in the dorsomedial grasp pathway, is involved in grasp movements. However, the neural ensemble firing property of PMd during grasp movements and the extent to which it can be used for grasp decoding are still unclear. Approach. To address these issues, we used multielectrode arrays to record both spike and local field potential (LFP) signals in PMd in macaque monkeys performing reaching and grasping of one of four differently shaped objects. Main results. Single and population neuronal activity showed distinct patterns during execution of different grip types. Cluster analysis of neural ensemble signals indicated that the grasp related patterns emerged soon (200-300 ms) after the go cue signal, and faded away during the hold period. The timing and duration of the patterns varied depending on the behaviors of individual monkey. Application of support vector machine model to stable activity patterns revealed classification accuracies of 94% and 89% for each of the two monkeys, indicating a robust, decodable grasp pattern encoded in the PMd. Grasp decoding using LFPs, especially the high-frequency bands, also produced high decoding accuracies. Significance. This study is the first to specify the neuronal population encoding of grasp during the time course of grasp. We demonstrate high grasp decoding performance in PMd. These findings, combined with previous evidence for reach related modulation studies, suggest that PMd may play an important role in generation and maintenance of grasp action and may be a suitable locus for brain-machine interface applications.

  10. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress

    Science.gov (United States)

    Gould, Elizabeth; Tanapat, Patima; McEwen, Bruce S.; Flügge, Gabriele; Fuchs, Eberhard

    1998-01-01

    Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and ≈80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience. PMID:9501234

  11. Thermoregulatory Responses of Febrile Monkeys During Microwave Exposure

    National Research Council Canada - National Science Library

    Adair, E

    1997-01-01

    .... In a controlled ambient temperature of 26 degrees C, autonomic mechanisms of heat production and heat loss were measured in febrile squirrel monkeys during 30-min exposures to 450 or 2450 MHz CW MW...

  12. A triaxial accelerometer monkey algorithm for optimal sensor placement in structural health monitoring

    Science.gov (United States)

    Jia, Jingqing; Feng, Shuo; Liu, Wei

    2015-06-01

    Optimal sensor placement (OSP) technique is a vital part of the field of structural health monitoring (SHM). Triaxial accelerometers have been widely used in the SHM of large-scale structures in recent years. Triaxial accelerometers must be placed in such a way that all of the important dynamic information is obtained. At the same time, the sensor configuration must be optimal, so that the test resources are conserved. The recommended practice is to select proper degrees of freedom (DOF) based upon several criteria and the triaxial accelerometers are placed at the nodes corresponding to these DOFs. This results in non-optimal placement of many accelerometers. A ‘triaxial accelerometer monkey algorithm’ (TAMA) is presented in this paper to solve OSP problems of triaxial accelerometers. The EFI3 measurement theory is modified and involved in the objective function to make it more adaptable in the OSP technique of triaxial accelerometers. A method of calculating the threshold value based on probability theory is proposed to improve the healthy rate of monkeys in a troop generation process. Meanwhile, the processes of harmony ladder climb and scanning watch jump are proposed and given in detail. Finally, Xinghai NO.1 Bridge in Dalian is implemented to demonstrate the effectiveness of TAMA. The final results obtained by TAMA are compared with those of the original monkey algorithm and EFI3 measurement, which show that TAMA can improve computational efficiency and get a better sensor configuration.

  13. Space representation for eye movements is more contralateral in monkeys than in humans

    OpenAIRE

    Kagan, Igor; Iyer, Asha; Lindner, Axel; Andersen, Richard A.

    2010-01-01

    Contralateral hemispheric representation of sensory inputs (the right visual hemifield in the left hemisphere and vice versa) is a fundamental feature of primate sensorimotor organization, in particular the visuomotor system. However, many higher-order cognitive functions in humans show an asymmetric hemispheric lateralization—e.g., right brain specialization for spatial processing—necessitating a convergence of information from both hemifields. Electrophysiological studies in monkeys and fun...

  14. Behavioral and physiological responses to subgroup size and number of people in howler monkeys inhabiting a forest fragment used for nature-based tourism.

    Science.gov (United States)

    Aguilar-Melo, Adriana R; Andresen, Ellen; Cristóbal-Azkarate, Jurgi; Arroyo-Rodríguez, Victor; Chavira, Roberto; Schondube, Jorge; Serio-Silva, Juan Carlos; Cuarón, Alfredo D

    2013-11-01

    Animals' responses to potentially threatening factors can provide important information for their conservation. Group size and human presence are potentially threatening factors to primates inhabiting small reserves used for recreation. We tested these hypotheses by evaluating behavioral and physiological responses in two groups of mantled howler monkeys (Alouatta palliata mexicana) at the "Centro Ecológico y Recreativo El Zapotal", a recreational forest reserve and zoo located in the Mexican state of Chiapas. Both groups presented fission-fusion dynamics, splitting into foraging subgroups which varied in size among, but not within days. Neither subgroup size nor number of people had an effect on fecal cortisol. Out of 16 behavioral response variables tested, the studied factors had effects on six: four were affected by subgroup size and two were affected by number of people. With increasing subgroup size, monkeys increased daily path lengths, rested less, increased foraging effort, and used more plant individuals for feeding. As the number of people increased, monkeys spent more time in lower-quality habitat, and less time engaged in social interactions. Although fecal cortisol levels were not affected by the factors studied, one of the monkey groups had almost twice the level of cortisol compared to the other group. The group with higher cortisol levels also spent significantly more time in the lower-quality habitat, compared to the other group. Our results suggest that particular behavioral adjustments might allow howler monkeys at El Zapotal to avoid physiological stress due to subgroup size and number of people. However, the fact that one of the monkey groups is showing increased cortisol levels may be interpreted as a warning sign, indicating that an adjustment threshold is being reached, at least for part of the howler monkey population in this forest fragment. © 2013 Wiley Periodicals, Inc.

  15. Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys

    International Nuclear Information System (INIS)

    Doerge, Daniel R.; Twaddle, Nathan C.; Woodling, Kellie A.; Fisher, Jeffrey W.

    2010-01-01

    Bisphenol A (BPA) is a high-production volume industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 is controversial because of the potential for endocrine disruption, particularly during perinatal development, as suggested by in vitro, experimental animal, and epidemiological studies. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal rhesus monkeys by oral (PND 5, 35, 70) and intravenous injection (PND 77) routes using d6-BPA to avoid sample contamination. The concentration-time profiles observed in adult monkeys following oral administration of 100 μg/kg bw were remarkably similar to those previously reported in human volunteers given a similar dose; moreover, minimal pharmacokinetic differences were observed between neonatal and adult monkeys for the receptor-active aglycone form of BPA. Circulating concentrations of BPA aglycone were quite low following oral administration (< 1% of total), which reflects the redundancy of active UDP-glucuronosyl transferase isoforms in both gut and liver. No age-related changes were seen in internal exposure metrics for aglycone BPA in monkeys, a result clearly different from developing rats where significant inverse age-related changes, based on immaturity of Phase II metabolism and renal excretion, were recently reported. These observations imply that any toxicological effect observed in rats from early postnatal exposures to BPA could over-predict those possible in primates of the same age, based on significantly higher internal exposures and overall immaturity at birth.

  16. Habitat quality of the woolly spider monkey (Brachyteles hypoxanthus).

    Science.gov (United States)

    da Silva Júnior, Wilson Marcelo; Alves Meira-Neto, João Augusto; da Silva Carmo, Flávia Maria; Rodrigues de Melo, Fabiano; Santana Moreira, Leandro; Ferreira Barbosa, Elaine; Dias, Luiz Gustavo; da Silva Peres, Carlos Augusto

    2009-01-01

    This study examines how habitat structure affects the home range use of a group of Brachyteles hypoxanthus in the Brigadeiro State Park, Brazil. It has been reported that most of the annual feeding time of woolly spider monkeys is spent eating leaves, but they prefer fruits when available. We hypothesise that the protein-to-fibre ratio (PF; best descriptor of habitat quality for folivorous primates) is a better descriptor of habitat quality and abundance for these primates than the structural attributes of forests (basal area is the best descriptor of habitat quality for frugivorous primates of Africa and Asia). We evaluated plant community structure, successional status, and PF of leaf samples from the dominant tree populations, both within the core and from a non-core area of the home range of our study group. Forest structure was a combination of stem density and basal area of dominant tree populations. The core area had larger trees, a higher forest basal area, and higher stem density than the non-core area. Mean PF did not differ significantly between these sites, although PF was influenced by differences in tree regeneration guilds. Large-bodied monkeys could be favoured by later successional stages of forests because larger trees and denser stems prevent the need for a higher expenditure of energy for locomotion as a consequence of vertical travel when the crowns of trees are disconnected in early successional forests. Forest structure variables (such as basal area of trees) driven by succession influence woolly spider monkey abundance in a fashion similar to frugivorous monkeys of Asia and Africa, and could explain marked differences in ranging behaviour and home range use by B. hypoxanthus. Copyright 2009 S. Karger AG, Basel.

  17. The influence of social structure on social isolation in amphetamine-treated Java monkeys (Macaca fascicularis).

    Science.gov (United States)

    Knobbout, D.A.; Ellenbroek, B.A.; Cools, A.R.

    1996-10-01

    Amphetamine-induced social isolation in monkeys has often been considered a valid animal model for certain negative symptoms of schizophrenia. However, there appear to be many ambiguities in relation to the exact nature of the isolation. Therefore, the effect of orally administered amphetamine (AMP) on the occurrence of social isolation in Java monkeys was studied. In part I the rank dependency of the effects of AMP (0.5mg/kg) was investigated in four alpha-males and three beta-males. AMP increased 'proximity' and 'passive groom', and decreased 'active allogroom' in alpha-males. In contrast, AMP decreased all three behavioural elements to a certain extent in beta-males. It is concluded that AMP induces social isolation in beta-males, but not in alpha-males. In part II of this study the AMP-induced behaviour of the treated monkey and the simultaneously occurring changes in the non-treated monkeys were investigated in a detailed study of a single social group. AMP significantly reduced the frequency of 'exploration', 'locomotion', 'self-groom', 'swing', 'active groom', 'inspect', 'approach' and originally-present stereotypies. Thus AMP apparently reduces the ability to initiate behaviour which is characteristic for the adult animal. AMP did not affect the frequency of 'present' and 'play' and enhanced that of 'aggression' and 'fear' in the beta-male; it also elicited various juvenile-like behaviours in both alpha- and beta-males, suggesting that AMP induces a behavioural regression. Furthermore, the behaviour of the non-treated monkeys of the group was decisive for the occurrence of social isolation of the treated monkey. Thus, the effects of AMP on the social behaviour of Java monkeys depend on the individual sensitivity, the social position which the subject occupies in its group, and the behaviour of the partners of the treated subject.

  18. An alert of Mycobacterium tuberculosis infection of rhesus macaques in a wild zoo in China.

    Science.gov (United States)

    Gong, Wenping; Yang, Yourong; Luo, Yi; Li, Ning; Bai, Xuejuan; Liu, Yinping; Zhang, Junxian; Chen, Ming; Zhang, Chenglin; Wu, Xueqiong

    2017-10-30

    Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB), is becoming increasingly recognized as an important cause of fatal chronic illnesses in China. In this study, we report an infectious disease among 84 rhesus macaques at a Chinese zoo. Their clinical signs and symptoms were very similar with the manifestations of TB in humans. To determine the potential pathogens of this outbreak, many methods were used. First, tuberculin skin tests showed that none of the monkeys displayed significant skin reactions. Subsequently, the sera were tested for specific antibody IgG; 29 (34.5%) and 39 (46.4%) blood samples tested positive by TB-IgG and TB-DOT, respectively. Radiographic examination showed characteristic imageology changes in 14 (16.7%) monkeys. One individual determined as positive by the above three methods was euthanized, and histopathological analysis demonstrated typical granulomas and caseous necrosis in the lung, liver, spleen, and intestine. Furthermore, the pathogenic mycobacteria were isolated from lung lobe, cultured on acidic Lowenstein-Jensen culture medium, and identified as M. tuberculosis by real-time PCR and DNA sequencing. Nevertheless, the origin of the infection remained unknown. These findings emphasize the need to strengthen the management and training of staff, especially those working at animal shelters.

  19. Phenobarbital treatments lower DDT body burden in rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, P.W.; Clark, C.R.; Gee, S.J.; Krieger, R.I.

    1981-01-01

    Decreased DDT, DDD, DDE in blood and DDA in urine followed phenobarbital treatments (10 mg/kg/day, 11 days, intramuscular (im)) in three male rhesus monkeys (Macaca mulatta). Animals were fed DDT diets containing up to 500 ppm DDT during a 3-year period. Induction of liver monooxygenases was confirmed by reduced in vivo antipyrine plasma half-life and increased in vitro oxidation rates of dihydroisodrin, p-nitroanisole and benz(alpha)pyrene by homogenates of liver obtained from closed needle biopsy. Chlorohydrocarbon blood levels significantly decreased during the induction period (days 1-11). Concentrations on day 28 were at or below pre-DDT exposure levels. Urine DDA gradually decreased in all monkeys from days 16 to 28.

  20. Pig as a Favorable Animal for Taenia Saginata Asiatica Infection

    Directory of Open Access Journals (Sweden)

    Ping-Chin Fan

    2006-01-01

    Full Text Available The epidemiology of Taenia saginata in some parts of Asia is confusing, in that beef does not appear to be the source of infection. In some areas, beef is either not available or not eaten raw, whereas pork at times is eaten uncooked. In light of this situation, we have exposed pigs and other animals to infection with strains of T. saginata to establish their ability to serve as intermediate hosts. Eggs of Taiwan Taenia, Korea Taenia, Indonesia Taenia, Thailand Taenia, Philippines Taenia, Ethiopia Taenia, and Madagascar Taenia were fed to 83 pigs of three strains: 43 Small-Ear Miniature (SEM, 34 Landrace Small-Ear Miniature (L-SEM, and 6 Duroc-Yorkshire-Landrace (DYL. We also fed the eggs to 10 Holstein calves, 17 Sannean goats, and 4 monkeys (Macaca cyclopis. We succeeded in infecting SEM (infection rate 88%, cysticercus recovery rate 19.1%, L-SEM (83%, 1.1%, and DYL (100%, 0.3% pigs with Taiwan Taenia; SEM (100%, 1.7%, L-SEM (100%, 5.6%, and DYL (100%, 0.06% pigs with Korea Taenia; SEM (100%, 22% and L-SEM (100%, 1.6% pigs with Indonesia Taenia; SEM (75%, 0.06% pigs with Thailand Taenia SEM (100%, 11% pigs with Philippines Taenia; SEM (80%, 0.005% pigs with Ethiopia Taenia; SEM (100%, 0.2% pigs with Madagascar Taenia. Holstein calves became infected with Taenia from Taiwan (100%, 1.1%, Korea (100%, 0.03%, Thailand (100%, 0.2%, and the Philippines (100%, 6%; however, the cysticerci of Taenia from Korea, Thailand, and the Philippines were degenerated and/or calcified. Sannean goats became infected with Taenia from Taiwan (33%, 0.01% and Korea (50%, 0.02%, while monkeys became infected with Taenia from Taiwan (50%, 0.01%. However, the cysticerci were degenerated and/or calcified. Therefore, these strains of pig seem to be favorable animal models for experimental studies of T. saginata-like tapeworms, with the SEM pig the most favorable.

  1. New Entamoeba group in howler monkeys (Alouatta spp.) associated with parasites of reptiles.

    Science.gov (United States)

    Villanueva-García, Claudia; Gordillo-Chávez, Elías José; Baños-Ojeda, Carlos; Rendón-Franco, Emilio; Muñoz-García, Claudia Irais; Carrero, Julio César; Córdoba-Aguilar, Alex; Maravilla, Pablo; Galian, José; Martínez-Hernández, Fernando; Villalobos, Guiehdani

    2017-08-01

    Our knowledge of the parasite species present in wildlife hosts is incomplete. Protozoans such as amoebae of the genus Entamoeba infect a large variety of vertebrate species, including NHPs. However, traditionally, their identification has been accomplished through microscopic evaluation; therefore, amoeba species have not always been identified correctly. We searched for Entamoeba spp. using a fragment of the small subunit rDNA in free-ranging howler monkeys (Alouatta palliata and A. pigra) from southeast Mexico. One hundred fifty five samples were collected, with 46 from A. palliata and 109 from A. pigra and 8 of the total samples were positive. We detected a new clade of Entamoeba, which was separated from other described species but closer to E. insolita, as well as an unnamed sequence typically found in iguana species with low shared identity values (reptiles.

  2. Subarachnoid administration of iohexol in cynomolgus monkeys

    International Nuclear Information System (INIS)

    Drobeck, H.P.; Mayes, B.A.; Barbolt, T.A.; Fabian, R.J.; Kimball, J.P.; Slighter, R.R. Jr.

    1986-01-01

    A non-ionic diagnostic medium, iohexol, was administered by subarachnoid injection to groups of six cynomolgus monkeys and compared with the vehicle, physiologically normal saline, and/or saline of equal osmolality to determine its potential for increasing total protein and leucocyte levels in cerebrospinal fluid. Also investigated was the effect of repeated spinal taps not subsequently followed by the intrathecal injection of test or control articles. In the monkey, unlike man, low-level leucocyte counts were consistently observed following initial withdrawal of spinal fluid. Elevated leucocyte and total protein levels were observed in the present investigations one day to a week after intrathecal injection of radiopaque, vehicle or saline solution. Total protein returned to normal levels earlier than did leucocyte counts. However, repeated needle puncture alone was found to be sufficient to cause an elevation of leucocytes 3 to 4 times the baseline level, while inflammatory effects were observed histologically only when autopsy was performed soon after the final spinal tap. (orig.)

  3. Timing of births in sympatric brown howler monkeys (Alouatta fusca clamitans) and northern muriquis (Brachyteles arachnoides hypoxanthus).

    Science.gov (United States)

    Strier, K B; Mendes, S L; Santos, R R

    2001-10-01

    We monitored the birth patterns of sympatric brown howler monkeys (Alouatta fusca clamitans) and northern muriquis (Brachyteles arachnoides hypoxanthus) during a 4-yr period from October 1996 to August 2000 at the Estação Biológica de Caratinga, Minas Gerais, Brazil. Brown howler monkey births (n = 34) occurred throughout the year, and birth frequencies did not differ between rainy and dry season months. The aseasonal birth patterns of the howler monkeys differed significantly from the dry season concentration and dry month peak in muriqui births (n = 23). We found no effects of infant sex or the number of females on interbirth intervals (IBIs) in our 10 howler monkey study troops. IBIs of brown howler monkeys averaged 21.2 +/- 2.5 mo (n = 8, median = 21.0 mo), and were significantly shorter following dry season births than rainy season births. Their IBIs and yearling survivorship (74%) were similar to those reported for other species of howler monkeys, but yearling survivorship was much lower than that of muriquis (94%), whose IBIs were more than 12 mo longer than those of the howler monkeys. Our study extends comparative knowledge of birth patterns in Alouatta to a poorly known species, and provides insights into the different ways in which diet and life history may affect the timing of births in large-bodied platyrrhines under the same seasonal ecological conditions. Copyright 2001 Wiley-Liss, Inc.

  4. Nature of the Refractive Errors in Rhesus Monkeys (Macaca mulatta) with Experimentally Induced Ametropias

    Science.gov (United States)

    Qiao-Grider, Ying; Hung, Li-Fang; Kee, Chea-su; Ramamirtham, Ramkumar; Smith, Earl L.

    2010-01-01

    We analyzed the contribution of individual ocular components to vision-induced ametropias in 210 rhesus monkeys. The primary contribution to refractive-error development came from vitreous chamber depth; a minor contribution from corneal power was also detected. However, there was no systematic relationship between refractive error and anterior chamber depth or between refractive error and any crystalline lens parameter. Our results are in good agreement with previous studies in humans, suggesting that the refractive errors commonly observed in humans are created by vision-dependent mechanisms that are similar to those operating in monkeys. This concordance emphasizes the applicability of rhesus monkeys in refractive-error studies. PMID:20600237

  5. Background and stimulus-induced patterns of high metabolic activity in the visual cortex (area 17) of the squirrel and macaque monkey

    International Nuclear Information System (INIS)

    Humphrey, A.L.; Hendrickson, A.E.

    1983-01-01

    We have used 2-deoxy-D-[ 14 C]glucose (2-DG) autoradiography and cytochrome oxidase histochemistry to examine background and stimulus-induced patterns of metabolic activity in monkey striate cortex. In squirrel monkeys (Saimiri sciureus) that binocularly or monocularly viewed diffuse white light or binocularly viewed bars of many orientations and spatial frequencies, 2-DG consumption was not uniform across the cortex but consisted of regularly spaced radial zones of high uptake. The zones extended through all laminae except IVc beta and, when viewed tangentially, formed separate patches 500 microns apart. The cytochrome oxidase stain in these animals also revealed patches of high metabolism which coincided with the 2-DG patches. Squirrel monkeys binocularly viewing vertical stripes showed parallel bands of increased 2-DG uptake in the cortex, while the cytochrome label in these animals remained patchy. When monkeys were kept in the dark during 2-DG exposure, 2-DG-labeled patches were not seen but cytochrome oxidase-positive patches remained. In macaque (Macaca nemestrina) monkeys, binocular stimulation with many orientations and spatial frequencies produced radial zones of high 2-DG uptake in layers I to IVa and VI. When viewed tangentially, these zones formed a dots-in-rows pattern with a spacing of 350 X 500 microns; cytochrome oxidase staining produced an identical pattern. Macaca differed from Saimiri in that monocular stimulation labeled alternate rows. These results indicate that there are radial zones of high background metabolism across squirrel and macaque monkey striate cortex. In Saimiri these zones do not appear to be related to an eye dominance system, while in Macaca they do. The presence of these zones of high metabolism may complicate the interpretation of 2-DG autoradiographs that result from specific visual stimuli

  6. Distribution of collateral fibers in the monkey cervical spinal cord detected with diffusion-weighted magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lundell, Henrik; Nielsen, Jens Bo; Ptito, Maurice

    2011-01-01

    techniques. We calculate the diffusion tensor and the persistent angular structure (PAS), a multi-fiber reconstruction technique, from high quality post mortem data of a perfusion-fixed vervet monkey cervical spinal cord sample and simulated crossing fiber data. Our results show that (i) cylindrical geometry...

  7. Molecular cloning and characterization of rhesus monkey platelet glycoprotein Ibα, a major ligand-binding subunit of GPIb-IX-V complex.

    Science.gov (United States)

    Qiao, Jianlin; Shen, Yang; Shi, Meimei; Lu, Yanrong; Cheng, Jingqiu; Chen, Younan

    2014-05-01

    Through binding to von Willebrand factor (VWF), platelet glycoprotein (GP) Ibα, the major ligand-binding subunit of the GPIb-IX-V complex, initiates platelet adhesion and aggregation in response to exposed VWF or elevated fluid-shear stress. There is little data regarding non-human primate platelet GPIbα. This study cloned and characterized rhesus monkey (Macaca Mullatta) platelet GPIbα. DNAMAN software was used for sequence analysis and alignment. N/O-glycosylation sites and 3-D structure modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS-MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin-induced platelet aggregation. Rhesus monkey GPIbα contains 2,268 nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey GPIbα nucleotide and protein sequences share 93.27% and 89.20% homology respectively, with human. Sequences encoding the leucine-rich repeats of rhesus monkey GPIbα share strong similarity with human, whereas PEST sequences and N/O-glycosylated residues vary. The GPIbα-binding residues for thrombin, filamin A and 14-3-3ζ are highly conserved between rhesus monkey and human. Platelet function analysis revealed monkey and human platelets respond similarly to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin where human platelets achieved 76% aggregation. However, monkey platelets aggregated in response to higher ristocetin doses. Monkey GPIbα shares strong homology with human GPIbα, however there are some differences in rhesus monkey platelet activation through GPIbα engagement, which need to be considered when using rhesus monkey platelet to investigate platelet GPIbα function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Constancy and variability in cortical structure. A study on synapses and dendritic spines in hedgehog and monkey.

    Science.gov (United States)

    Schüz, A; Demianenko, G P

    1995-01-01

    Synapses and dendritic spines were investigated in the parietal cortex of the hedgehog (Erinaceus europaeus) and the monkey (Macaca mulatta). There was no significant difference in the density of synapses between the two species (14 synapses/100 microns2 in the hedgehog, 15/100 microns2 in the monkey), neither in the size of the synaptic junctions, in the proportion of Type I and Type II synapses (8-10% were of Type II in the hedgehog, 10-14% in the monkey) nor in the proportion of perforated synapses (8% in the hedgehog, 5% in the monkey). The only striking difference at the electron microscopic level concerned the frequency of synapses in which the postsynaptic profile was deeply indented into the presynaptic terminal. Such synapses were 10 times more frequent in the monkey. Dendritic spines were investigated in Golgi-preparations. The density of spines along dendrites was similar in both species. The results are discussed with regard to connectivity in the cortex of small and large brains.

  9. Long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.

    Science.gov (United States)

    Wang, B; Sun, G; Qiao, W; Liu, Y; Qiao, J; Ye, W; Wang, H; Wang, X; Lindquist, R; Wang, Y; Xiao, Y-F

    2017-09-01

    Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure. Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks. Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp. Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.

  10. The Effect Of SEA On Long Tail Monkeys (Macaca Fascicularis) Lymphocyte Culture Gamma Ray-Irradiated In Vitro

    International Nuclear Information System (INIS)

    Wa'id, Abdul; Lusiyanti, Yanti

    2000-01-01

    Staphylococus enteroxine (SEA) is one of toxins produced by the bacterium Staphylococus aureus. In the culture, SEA has proven as a potent stimulator of lymphocytes in man event at fg/ml concentrations. This research studied the effect of SEA compared to Phytohaemagglutinine (PHA) on the peripheral blood lymphocytes culture of the long-tail monkeys. About 5 ml blood was collected from 5 monkeys and irradiated using Gamma Cell-220 P3TIR with doses of 0 (control); 1.0; 2.0; 3.0 and 4.0 Gy. The blood samples were cultured in the appropriate growth medium based on standard procedure and added with 1.0 ml (0.5 mug/ml) SEA or 0.15 ml PHA. The cultures were then incubated for 96 hours and prepared the slides. The results showed that on the unirradiated peripheral blood lymphocytes of long-tail monkeys the mitotic indices obtained using PHA and SEA are relatively similar. On the irradiated lymphocytes with doses of 1-3 Gy, the mitotic indices using SEA are relatively higher than that of PHA. Dose responses of dicentric, ring and acentric fragment of both PHA and SEA are relatively the same

  11. Variability in core areas of spider monkeys (Ateles geoffroyi) in a tropical dry forest in Costa Rica.

    Science.gov (United States)

    Asensio, Norberto; Schaffner, Colleen M; Aureli, Filippo

    2012-04-01

    Core areas are highly used parts of the home range on which the survival of solitary or group-living animals depends. We investigated the home range and core area size and area fidelity of a spider monkey community in a tropical dry forest over a 4-year period. Home ranges overlapped extensively across years, subgroup sizes, and seasons. In contrast, spider monkeys used core areas that varied in size and location across the study years, subgroup sizes, and seasons. These shifts in core areas suggest that the understanding of core areas, and thus the spatial requirements, of a species in a particular habitat may be limited if based on short-term studies. In this respect, our findings emphasize the importance of long-term studies of the spatial ecology of any species in a particular habitat. Our study also shows that the yearly home range basically includes all the core areas from different years, seasons, and subgroup sizes (i.e., the super-core area). This is conceptually important for territorial species, such as spider monkeys, which defend a stable home range as it contains not only the current, but also the future core areas.

  12. Effect of an obesogenic diet on circadian activity and serum hormones in old monkeys

    Directory of Open Access Journals (Sweden)

    Henryk F Urbanski

    2017-07-01

    Full Text Available Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD. Old female rhesus macaques were ovo-hysterectomized (OvH to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E, beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS. These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.

  13. Responsiveness in Behaving Monkeys and Human Subjects

    Science.gov (United States)

    1993-07-31

    Status of Current Research - Statement of Work Each study involving awake , behaving monkey neurophysiological recording used a behavioral paradigm that...anesthesia. A craniotomy was performed at approximately A+ 14.5mm. The recording chamber then was fixed to the skull at a lateral angle of 8’ from

  14. Adaptive genetic variation at three loci in South African vervet monkeys (Chlorocebus pygerythrus and the role of selection within primates

    Directory of Open Access Journals (Sweden)

    Willem G. Coetzer

    2018-06-01

    Full Text Available Vervet monkeys (Chlorocebus pygerythrus are one of the most widely distributed non-human primate species found in South Africa. They occur across all the South African provinces, inhabiting a large variety of habitats. These habitats vary sufficiently that it can be assumed that various factors such as pathogen diversity could influence populations in different ways. In turn, these factors could lead to varied levels of selection at specific fitness linked loci. The Toll-like receptor (TLR gene family, which play an integral role in vertebrate innate immunity, is a group of fitness linked loci which has been the focus of much research. In this study, we assessed the level of genetic variation at partial sequences of two TLR loci (TLR4 and 7 and a reproductively linked gene, acrosin (ACR, across the different habitat types within the vervet monkey distribution range. Gene variation and selection estimates were also made among 11–21 primate species. Low levels of genetic variation for all three gene regions were observed within vervet monkeys, with only two polymorphic sites identified for TLR4, three sites for TLR7 and one site for ACR. TLR7 variation was positively correlated with high mean annual rainfall, which was linked to increased pathogen abundance. The observed genetic variation at TLR4 might have been influenced by numerous factors including pathogens and climatic conditions. The ACR exonic regions showed no variation in vervet monkeys, which could point to the occurrence of a selective sweep. The TLR4 and TLR7 results for the among primate analyses was mostly in line with previous studies, indicating a higher rate of evolution for TLR4. Within primates, ACR coding regions also showed signs of positive selection, which was congruent with previous reports on mammals. Important additional information to the already existing vervet monkey knowledge base was gained from this study, which can guide future research projects on this highly

  15. Experimental study of the role of blocking of 5-HT3 serotonin receptors and D2 dophamin receptors in the mechanism of early radiation vomiting in monkeys

    International Nuclear Information System (INIS)

    Martirosov, K.S.; Grigor'ev, Yu.G.; Zorin, V.V.; Andrianova, I.E.

    2000-01-01

    Specific activity of Latranum and Dimetphramidum is studied using experimental model of early radiation vomiting on 17 monkeys, mass 6-9 kg inherent on usual ration of vivarium. The experiments with M. fasciculata monkeys exposed to 137 Cs γ-radiation with a dose of 6.9 Gy showed that Latranum, a blocker of serotonin 5-HT 3 receptors, is a more efficient antimetric than Dimetphramidum, a D 2 dophamin lytic. This suggested by fewer animals with emetic reaction of by less severe vomiting in case they have any. The results agree well with a hypothesis that serotonin receptors are dominant in the chemoreceptor trigger zone of monkeys [ru

  16. Analogical reasoning and the differential outcome effect: transitory bridging of the conceptual gap for rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Flemming, Timothy M; Thompson, Roger K R; Beran, Michael J; Washburn, David A

    2011-07-01

    Monkeys, unlike chimpanzees and humans, have a marked difficulty acquiring relational matching-to-sample (RMTS) tasks that likely reflect the cognitive foundation upon which analogical reasoning rests. In the present study, rhesus monkeys (Macaca mulatta) completed a categorical (identity and nonidentity) RMTS task with differential reward (pellet ratio) and/or punishment (timeout ratio) outcomes for correct and incorrect choices. Monkeys in either differential reward-only or punishment-only conditions performed at chance levels. However, the RMTS performance of monkeys experiencing both differential reward and punishment conditions was significantly better than chance. Subsequently when all animals experienced nondifferential outcomes tests, their RMTS performance levels were at chance. These results indicate that combining differential reward and punishment contingencies provide an effective, albeit transitory, scaffolding for monkeys to judge analogical relations-between-relations. PsycINFO Database Record (c) 2011 APA, all rights reserved

  17. [Blood plasma volume dynamics in monkeys during immersion].

    Science.gov (United States)

    Krotov, V P; Burkovskaia, T E; Dotsenko, M A; Gordeev, Iu V; Nosovskiĭ, A M; Chel'naia, N A

    2004-01-01

    Dynamics of blood plasma volume (PV) was studied with indirect methods (hematocrit count, hemoglobin, total protein and high-molecular protein) during 9-d immersion of monkeys Macaca mulatta. The animals were donned in waterproof suits, motor restrained in space seat liners and immersed down to the xiphisternum. Two monkeys were immersed in the bath at one time. The suits were changed every day under ketamine (10 mg/kg of body mass). There were two groups with 12 animals in each. The first group was kept in the bath 3 days and the second--9 days. Prior to the experiment, the animals had been trained to stay in the seat liner put down into the dry bath. It was shown that already two days of exposure to the hydrostatic forces (approximately 15 mm Hg) and absence of negative pressure breathing reduced PV by 18-20% on the average in all animals. Subsequent PV dynamics was individual by character; however, PV deficit persisted during 4 days of immersion in the whole group. In this period, albumin filtration was increased significantly, whereas high-molecular protein filtration was increased to a less degree. During the remaining days in immersion PV regained normal values. Ten days of readaptation (reclined positioning of monkeys brought back into cage) raised VP beyond baseline values. This phenomenon can be attributed to the necessity to provide appropriate venous return and sufficient blood supply of organs and tissues following extension of blood vessels capacity.

  18. Chitinase mRNA Levels Determined by QPCR in Crab-Eating Monkey (Macaca fascicularis) Tissues: Species-Specific Expression of Acidic Mammalian Chitinase and Chitotriosidase.

    Science.gov (United States)

    Uehara, Maiko; Tabata, Eri; Ishii, Kazuhiro; Sawa, Akira; Ohno, Misa; Sakaguchi, Masayoshi; Matoska, Vaclav; Bauer, Peter O; Oyama, Fumitaka

    2018-05-09

    Mice and humans express two active chitinases: acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Both chitinases are thought to play important roles in specific pathophysiological conditions. The crab-eating monkey ( Macaca fascicularis ) is one of the most frequently used nonhuman primate models in basic and applied biomedical research. Here, we performed gene expression analysis of two chitinases in normal crab-eating monkey tissues by way of quantitative real-time polymerase chain reaction (qPCR) using a single standard DNA molecule. Levels of AMCase and CHIT1 messenger RNAs (mRNAs) were highest in the stomach and the lung, respectively, when compared to other tissues. Comparative gene expression analysis of mouse, monkey, and human using monkey⁻mouse⁻human hybrid standard DNA showed that the AMCase mRNA levels were exceptionally high in mouse and monkey stomachs while very low in the human stomach. As for the CHIT1 mRNA, we detected higher levels in the monkey lung when compared with those of mouse and human. The differences of mRNA expression between the species in the stomach tissues were basically reflecting the levels of the chitinolytic activities. These results indicate that gene expression of AMCase and CHIT1 differs between mammalian species and requiring special attention in handling data in chitinase-related studies in particular organisms.

  19. Autoradiographic studies on the effect of allopurinol on 14C-hydpoxanthine metabolism in the squirrel monkey

    International Nuclear Information System (INIS)

    Matsunaga, Yoshimasa; Miyazaki, Hisashi; Hashimoto, Masahisa

    1980-01-01

    The Effect of orally given allopurinol on the distribution of intravenously administered 14 C-hypoxanthine radioactivity was studied in squirrel monkeys 8 hr after administration of the label by the whole body autoradiography. Although the distribution of radioactivity in the normal and allopurinol-treated animals was essentially similar to each other, more intense radioactivity was noted in the latter monkey; salvage of 14 C-hypoxanthine was enhanced. Similarly to our previous observation in mice, significant radioactivity in monkeys was seen in tissues undergoing rapid nucleic acid synthesis except for slight species differences in some organs. 14 C-Allantoin alone was the urinary metabolite of the hypoxanthine in the normal monkey whereas significant amounts of 14 C-hypoxanthine and 14 C-xanthine as well were detected in the urine of the drug-treated animal. (author)

  20. Effects of heated hydrotherapy on muscle HSP70 and glucose metabolism in old and young vervet monkeys.

    Science.gov (United States)

    Kavanagh, Kylie; Davis, Ashely T; Jenkins, Kurt A; Flynn, D Mickey

    2016-07-01

    Increasing heat shock protein 70 (HSP70) in aged and/or insulin-resistant animal models confers benefits to healthspan and lifespan. Heat application to increase core temperature induces HSPs in metabolically important tissues, and preliminary human and animal data suggest that heated hydrotherapy is an effective method to achieve increased HSPs. However, safety concerns exist, particularly in geriatric medicine where organ and cardiovascular disease commonly will preexist. We evaluated young vervet monkeys compared to old, insulin-resistant vervet monkeys (Chlorocebus aethiops sabaeus) in their core temperatures, glucose tolerance, muscle HSP70 level, and selected safety biomarkers after 10 sessions of hot water immersions administered twice weekly. Hot water immersion robustly induced the heat shock response in muscles. We observed that heat-treated old and young monkeys have significantly higher muscle HSP70 than control monkeys and treatment was without significant adverse effects on organ or cardiovascular health. Heat therapy improved pancreatic responses to glucose challenge and tended to normalize glucose excursions. A trend for worsened blood pressure and glucose values in the control monkeys and improved values in heat-treated monkeys were seen to support further investigation into the safety and efficacy of this intervention for metabolic syndrome or diabetes in young or old persons unable to exercise.

  1. Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

    Science.gov (United States)

    Itoh, Kosuke; Nejime, Masafumi; Konoike, Naho; Nakada, Tsutomu; Nakamura, Katsuki

    2015-09-01

    Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Auditory Association Cortex Lesions Impair Auditory Short-Term Memory in Monkeys

    Science.gov (United States)

    Colombo, Michael; D'Amato, Michael R.; Rodman, Hillary R.; Gross, Charles G.

    1990-01-01

    Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

  3. Cyto-, myelo- and chemoarchitecture of the prefrontal cortex of the Cebus monkey

    Science.gov (United States)

    2011-01-01

    Background According to several lines of evidence, the great expansion observed in the primate prefrontal cortex (PfC) was accompanied by the emergence of new cortical areas during phylogenetic development. As a consequence, the structural heterogeneity noted in this region of the primate frontal lobe has been associated with diverse behavioral and cognitive functions described in human and non-human primates. A substantial part of this evidence was obtained using Old World monkeys as experimental model; while the PfC of New World monkeys has been poorly studied. In this study, the architecture of the PfC in five capuchin monkeys (Cebus apella) was analyzed based on four different architectonic tools, Nissl and myelin staining, histochemistry using the lectin Wisteria floribunda agglutinin and immunohistochemistry using SMI-32 antibody. Results Twenty-two architectonic areas in the Cebus PfC were distinguished: areas 8v, 8d, 9d, 12l, 45, 46v, 46d, 46vr and 46dr in the lateral PfC; areas 11l, 11m, 12o, 13l, 13m, 13i, 14r and 14c in the orbitofrontal cortex, with areas 14r and 14c occupying the ventromedial corner; areas 32r, 32c, 25 and 9m in the medial PfC, and area 10 in the frontal pole. This number is significantly higher than the four cytoarchitectonic areas previously recognized in the same species. However, the number and distribution of these areas in Cebus were to a large extent similar to those described in Old World monkeys PfC in more recent studies. Conclusions The present parcellation of the Cebus PfC considerably modifies the scheme initially proposed for this species but is in line with previous studies on Old World monkeys. Thus, it was observed that the remarkable anatomical similarity between the brains of genera Macaca and Cebus may extend to architectonic aspects. Since monkeys of both genera evolved independently over a long period of time facing different environmental pressures, the similarities in the architectonic maps of PfC in both genera

  4. Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

    International Nuclear Information System (INIS)

    Melchior, G.W.; Castle, C.K.

    1989-01-01

    Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD [apo A-I(50 kD)], whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range [apo A-I(LDL)]. The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species

  5. Hemopoietic stem cells in rhesus monkeys : surface antigens, radiosensitivity, and responses to GM-CSF

    NARCIS (Netherlands)

    J.J. Wielenga (Jenne)

    1990-01-01

    textabstractRhesus monkeys (Macaca mulatta) were bred at the Primate Center TNO, Rijswijk, The Netherlands!. Both male and female animals were used for the experiments. The monkeys weighed 2.5-4 kg and were 2-4 years old at the time of the experiment. They were all typed for RhLA-A, -B and -DR

  6. PET measurement of FK506 concentration in a monkey model of stroke

    International Nuclear Information System (INIS)

    Murakami, Yoshihiro; Takamatsu, Hiroyuki; Noda, Akihiro; Osoda, Kazuhiko; Nishimura, Shintaro

    2007-01-01

    Introduction: The immunosuppressive agent FK506 (tacrolimus) has neuroprotective properties in an experimental model of cerebral ischemia. To improve the accuracy of clinical studies in acute stroke, a clinical dose setting should be based on the brain concentration, but not on the blood concentration of agents in humans. We have already established a measurement method using PET for FK506 concentration in the normal monkey brain, which could be applicable for human study; however, under ischemic conditions, in this study, we aimed to examine the brain concentration of FK506 in a monkey model of stroke. Methods: Studies were performed on six male cynomolgus monkeys (Macaca fascicularis) and a middle cerebral artery (MCA) occlusion model was used. Regional cerebral blood flow (rCBF) was measured by an intravenous injection of [ 15 O]H 2 O 165 min after MCA occlusion. FK506 (0.1 mg/kg) containing [ 11 C]FK506 was intravenously injected into the monkeys 180 min after MCA occlusion, and dynamic PET images were acquired for 30 min after administration. FK506 concentrations in the brain were calculated in moles per liter (M) units using the specific activity of injected FK506. Results: MCA occlusion produced ischemia, confirmed by rCBF measurement before the administration of [ 11 C]FK506. Fifteen minutes after FK506 (0.1 mg/kg) administration, the concentrations in the contralateral and ipsilateral cortex were 22.4±6.4 and 19.7±4.0 ng/g, respectively. Conclusion: We successfully measured the brain concentration of FK506 in a monkey model of stroke. The difference between the contralateral and ipsilateral concentrations of FK506 was not significant. This characteristic that FK506 readily penetrates ischemic tissue as well as normal tissue might explain the neuroprotective effect of FK506 in the ischemic brain and is suitable for the treatment of stroke patients

  7. Comparative response of dogs and monkeys to sublethal acute and continuous low dose-rate gamma-ray exposure

    International Nuclear Information System (INIS)

    Spalding, J.F.; Holland, L.M.; Johnson, O.S.; LaBauve, P.M.; London, J.E.; Prine, J.R.; Vigil, E.A.

    1977-02-01

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (injury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with 35 R/day until death to determine the amount of radiation-induced injury remaining in conditioned animals as a reduction in mean survival time. Dogs (50 percent) and monkeys (8 percent) died from injury incurred during the conditioning exposures. Thus, the comparative response of dogs and monkeys to dose protraction by acute dose fractionation was similar to what might be expected from a single acute dose. Mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approximately 1400 h). Thus, hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35 R/day gamma-ray challenge exposure were greater than for their control counterparts. Thus, the long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than four times the acute LD 50 - 30 in dogs and approximately two times that of monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 R/day

  8. A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments.

    Science.gov (United States)

    Khachaturian, Mark Haig

    2010-01-01

    Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).

  9. Establishment of reference values for complete blood count and blood gases in cynomolgus monkeys (Macaca fascicularis)

    Science.gov (United States)

    NAKAYAMA, Shunya; KOIE, Hiroshi; KANAYAMA, Kiichi; KATAKAI, Yuko; ITO-FUJISHIRO, Yasuyo; SANKAI, Tadashi; YASUTOMI, Yasuhiro; AGEYAMA, Naohide

    2017-01-01

    Cynomolgus monkeys are closely related to humans phylogenetically, and this has resulted in their widespread use as a preclinical model. Hematological data with regard to these monkeys are thus important. Although reference values for blood components and sex hormones have been established for cynomolgus monkeys, those for arterial blood gases have not. The arterial blood gases quickly reflect respiratory and circulatory dynamics, and are thus useful for animal management and safe general anesthesia and surgical operations. Furthermore, since O2 is transported by RBC, CBC and blood gases are closely related. The present study aimed to establish reference values for arterial blood gases and CBC in cynomolgus monkeys over a wide age range. Blood gases and CBC of arterial blood, collected from 41 female and 21 male anesthetized monkeys, were measured. Age correlated with RBC, HGB and HCT in the CBC. Values differed significantly between males and females in pCO2, CO2 concentration, MCV and MCH. The pH of blood was equivalent to that of humans and pCO2 was more stable, whereas MCV and MCH were lower than those in humans. Erythrocytes were smaller and less pigmented than in other Macaca species. Several relationships between gender and age, and blood gases and CBC were identified in cynomolgus monkeys. In conclusion, these reference values will be useful as markers for veterinary applications and in the care and maintenance of these animals. PMID:28381665

  10. Effect of environmental enrichment devices on behaviors of single- and group-housed squirrel monkeys (Saimiri sciureus)

    Science.gov (United States)

    Spring, S. E.; Clifford, J. O.; Tomko, D. L.

    1997-01-01

    Squirrel monkeys display an interest in novel places, habituate to new situations, and spend most of their daily activity in the wild in large groups engaging in feeding behaviors over a broad area. Captivity limits these behaviors and consequently may disrupt normal social organizations. In captivity, squirrel monkeys may exhibit stereotypical behaviors that are believed to indicate decreased psychologic well-being. When a monkey's behavior can be made to approach that seen in the wild, and stereotypical behaviors are minimal, it is assumed that psychologic well-being is adequate. Environmental enrichment devices have been used to address the Animal Welfare Act requirement that psychologic well-being of captive nonhuman primates be considered. The purpose of the study reported here was to examine whether various environmental enrichment devices improve the psychologic well-being of captive squirrel monkeys. In the study, we used behavioral observation to quantify the effectiveness of several environmental enrichment devices for reducing stereotypical behaviors in squirrel monkeys housed alone or in groups. Analysis of our results revealed that the environmental enrichment devices did not affect the expression of normal or stereotypical behaviors, but that the type of housing did.

  11. Age-Specific Gene Expression Profiles of Rhesus Monkey Ovaries Detected by Microarray Analysis

    Directory of Open Access Journals (Sweden)

    Hengxi Wei

    2015-01-01

    Full Text Available The biological function of human ovaries declines with age. To identify the potential molecular changes in ovarian aging, we performed genome-wide gene expression analysis by microarray of ovaries from young, middle-aged, and old rhesus monkeys. Microarray data was validated by quantitative real-time PCR. Results showed that a total of 503 (60 upregulated, 443 downregulated and 84 (downregulated genes were differentially expressed in old ovaries compared to young and middle-aged groups, respectively. No difference in gene expression was found between middle-aged and young groups. Differentially expressed genes were mainly enriched in cell and organelle, cellular and physiological process, binding, and catalytic activity. These genes were primarily associated with KEGG pathways of cell cycle, DNA replication and repair, oocyte meiosis and maturation, MAPK, TGF-beta, and p53 signaling pathway. Genes upregulated were involved in aging, defense response, oxidation reduction, and negative regulation of cellular process; genes downregulated have functions in reproduction, cell cycle, DNA and RNA process, macromolecular complex assembly, and positive regulation of macromolecule metabolic process. These findings show that monkey ovary undergoes substantial change in global transcription with age. Gene expression profiles are useful in understanding the mechanisms underlying ovarian aging and age-associated infertility in primates.

  12. The Macaque Social Responsiveness Scale (mSRS: A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Eric J Feczko

    Full Text Available Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD, has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS. Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological

  13. Correlation between the concentration of serum polychlorinated biphenyls (PCBs) in pregnant cynomolgus monkeys and their offspring's behavioral scores in eye-contact test and finger maze learning test

    Energy Technology Data Exchange (ETDEWEB)

    Negishi, T. [Aoyama Gakuin Univ., Kanagawa (Japan); Takasuga, T. [Shimadzu Techno-Research Inc., Kyoto (Japan); Kawasaki, K. [Hoshi Univ., Tokyo (Japan); Kuroda, Y. [CREST Japan Science and Technology Corp., Saitama (Japan); Yoshikawa, Y. [The Univ. of Tokyo (Japan)

    2004-09-15

    A recent review suggested that pre- or perinatal exposure of developing fetuses to dioxins, the widespread environmental contaminants, such as polychrorinated biphenlys (PCBs), induce the irreversible abnormalities in the functions of central nervous system (CNS) in human. These chemicals can be transferred to each fetus and naonate transplacentally and lactationally in rhesus monkey. Several studies also reported the adverse effect of PCB on CNS development in rodents and monkeys as well as on behavior in rodents and monkeys. In the present study, we show a preliminary data about the correlation between the serum concentrations of PCBs in pregnant cynomolgus monkeys (Macaca fascicularis) and the scores of two behavioral tests, eye-contact test and four-step finger maze test, which evaluate consciousness against human observer and learning ability, respectively, in their offspring. This experimental surveillance system using non-human primates would be useful to predict the risk of PCBs exposure in human fetuses because of the similarities of cynomolgus monkey to human with regard to reproduction, developmental parameter, and others.

  14. Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex

    Science.gov (United States)

    Hadj-Bouziane, Fadila; Liu, Ning; Bell, Andrew H.; Gothard, Katalin M.; Luh, Wen-Ming; Tootell, Roger B. H.; Murray, Elisabeth A.; Ungerleider, Leslie G.

    2012-01-01

    We previously showed that facial expressions modulate functional MRI activity in the face-processing regions of the macaque monkey’s amygdala and inferior temporal (IT) cortex. Specifically, we showed that faces expressing emotion yield greater activation than neutral faces; we term this difference the “valence effect.” We hypothesized that amygdala lesions would disrupt the valence effect by eliminating the modulatory feedback from the amygdala to the IT cortex. We compared the valence effects within the IT cortex in monkeys with excitotoxic amygdala lesions (n = 3) with those in intact control animals (n = 3) using contrast agent-based functional MRI at 3 T. Images of four distinct monkey facial expressions—neutral, aggressive (open mouth threat), fearful (fear grin), and appeasing (lip smack)—were presented to the subjects in a blocked design. Our results showed that in monkeys with amygdala lesions the valence effects were strongly disrupted within the IT cortex, whereas face responsivity (neutral faces > scrambled faces) and face selectivity (neutral faces > non-face objects) were unaffected. Furthermore, sparing of the anterior amygdala led to intact valence effects in the anterior IT cortex (which included the anterior face-selective regions), whereas sparing of the posterior amygdala led to intact valence effects in the posterior IT cortex (which included the posterior face-selective regions). Overall, our data demonstrate that the feedback projections from the amygdala to the IT cortex mediate the valence effect found there. Moreover, these modulatory effects are consistent with an anterior-to-posterior gradient of projections, as suggested by classical tracer studies. PMID:23184972

  15. Cognitive performance of juvenile monkeys after chronic fluoxetine treatment.

    Science.gov (United States)

    Golub, Mari S; Hackett, Edward P; Hogrefe, Casey E; Leranth, Csaba; Elsworth, John D; Roth, Robert H

    2017-08-01

    Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood. In this study, male juvenile rhesus monkeys (three-four years of age) were dosed with fluoxetine or vehicle (N=16/group) for two years. Histomorphometric examination of cortical dendritic spines conducted after euthanasia at one year postdosing (N=8/group) suggested a trend toward greater dendritic spine synapse density in prefrontal cortex of the fluoxetine-treated monkeys. During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention. After dosing was discontinued, sustained attention, recognition memory and cognitive flexibility were evaluated. Sustained attention was affected by fluoxetine, both during and after dosing, as indexed by omission errors. Response accuracy was not affected by fluoxetine in post-dosing recognition memory and cognitive flexibility tests, but formerly fluoxetine-treated monkeys compared to vehicle controls had more missed trial initiations and choices during testing. Drug treatment also interacted with genetic and environmental variables: MAOA genotype (high- and low transcription rate polymorphisms) and testing location (upper or lower tier of cages). Altered development of top-down cortical regulation of effortful attention may be relevant to this pattern of cognitive test performance after juvenile fluoxetine treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Toxoplasmosis in a colony of New World monkeys

    DEFF Research Database (Denmark)

    Dietz, H.H.; Henriksen, P.; Bille-Hansen, Vivi

    1997-01-01

    In a colony of New World monkeys five tamarins (Saguinus oedipus, Saguinus labiatus and Leontopithecus rosal. rosal.), three marmosets (Callithrix jacchus and Callithrix pygmaea) and one saki (Pithecia pithecia) died suddenly. The colony comprised 16 marmosets, 10 tamarins and three sakis. The ma...

  17. Comparative anatomy of the arm muscles of the Japanese monkey (Macaca fuscata) with some comments on locomotor mechanics and behavior.

    Science.gov (United States)

    Aversi-Ferreira, Tales Alexandre; Aversi-Ferreira, Roqueline A G M F; Bretas, Rafael Vieira; Nishimaru, Hiroshi; Nishijo, Hisao

    2016-08-01

    The anatomical literature on the genus Macaca has focused mainly on the rhesus monkey. However, some aspects in the positional behaviors of the Japanese monkey may be different from those in rhesus monkey, suggesting that the anatomical details of these species are divergent. Four thoracic limbs of Macaca fuscata adults were dissected. The arm muscles in Japanese macaques are more similar to rhesus monkeys and Papio; these characteristics are closer to those of bearded capuchins than apes, indicating more proximity of this genus to New World primates. The anatomical features observed favor quadrupedal locomotor behaviors on the ground and in arboreal environments. Japanese monkeys, rhesus monkeys, and bearded capuchins, which share more primitive characteristics in their arm muscles, present features that favor both arboreal and quadrupedal locomotor behaviors, whereas apes, mainly Pan and Gorilla, which spend more time on the ground, present more quadrupedal specializations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys.

    Science.gov (United States)

    Xu, Ning; Kwon, Soonil; Abbott, David H; Geller, David H; Dumesic, Daniel A; Azziz, Ricardo; Guo, Xiuqing; Goodarzi, Mark O

    2011-01-01

    The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD Pexcess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.

  19. Population coding of forelimb joint kinematics by peripheral afferents in monkeys.

    Directory of Open Access Journals (Sweden)

    Tatsuya Umeda

    Full Text Available Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates.

  20. First North American fossil monkey and early Miocene tropical biotic interchange

    Science.gov (United States)

    Bloch, Jonathan I.; Woodruff, Emily D.; Wood, Aaron R.; Rincon, Aldo F.; Harrington, Arianna R.; Morgan, Gary S.; Foster, David A.; Montes, Camilo; Jaramillo, Carlos A.; Jud, Nathan A.; Jones, Douglas S.; MacFadden, Bruce J.

    2016-05-01

    New World monkeys (platyrrhines) are a diverse part of modern tropical ecosystems in North and South America, yet their early evolutionary history in the tropics is largely unknown. Molecular divergence estimates suggest that primates arrived in tropical Central America, the southern-most extent of the North American landmass, with several dispersals from South America starting with the emergence of the Isthmus of Panama 3-4 million years ago (Ma). The complete absence of primate fossils from Central America has, however, limited our understanding of their history in the New World. Here we present the first description of a fossil monkey recovered from the North American landmass, the oldest known crown platyrrhine, from a precisely dated 20.9-Ma layer in the Las Cascadas Formation in the Panama Canal Basin, Panama. This discovery suggests that family-level diversification of extant New World monkeys occurred in the tropics, with new divergence estimates for Cebidae between 22 and 25 Ma, and provides the oldest fossil evidence for mammalian interchange between South and North America. The timing is consistent with recent tectonic reconstructions of a relatively narrow Central American Seaway in the early Miocene epoch, coincident with over-water dispersals inferred for many other groups of animals and plants. Discovery of an early Miocene primate in Panama provides evidence for a circum-Caribbean tropical distribution of New World monkeys by this time, with ocean barriers not wholly restricting their northward movements, requiring a complex set of ecological factors to explain their absence in well-sampled similarly aged localities at higher latitudes of North America.

  1. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations

    International Nuclear Information System (INIS)

    Ataya, K.; Pydyn, E.; Ramahi-Ataya

    1995-01-01

    With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation-induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E 2 ) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E 2 dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa-loaded minipump was removed (after the end of radiation). Serum E 2 increased after the end of LHRHa treatment in the non-irradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. 58 refs., 2 figs., 1 tab

  2. Dental disorders in brown howler monkeys (Alouatta guariba clamitans) maintained in captivity.

    Science.gov (United States)

    Dias Neto, Ramiro das Neves; Fecchio, Roberto Silva; Rahal, Sheila Canevese; Teixeira, Carlos Roberto; Gioso, Marco Antônio; Pereira, Camila Trevisan; Santos, Maria Augusta Adami Pereira Dos; Milanelo, Liliane

    2016-04-01

    The aim of this study was to investigate dental disorders of brown howler monkeys maintained in captivity. The hypothesis is that the identification and diagnosis of the lesions may contribute to control and prevention. Sixteen intact brown howler monkeys (Alouatta guariba clamitans), eight females and eight males, weighing from 3.9 to 6.8 kg, were studied. Under general anesthesia, the teeth were evaluated by visual inspection, probing, palpation, and intra-oral radiographic exam. The findings were registered on a dental chart specific for primates. Of the 16 monkeys evaluated in the present study, 94% (n = 15) had some type of dental disorder. The lesions observed were dental calculus (88%), dental wear (81%), missing teeth (38%), gingivitis (19%), gingival recession (6%), dental fracture (19%), pulp exposure (19%), and dental staining (25%). Alouatta guariba clamitans maintained in captivity have a high rate of dental problems. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    Science.gov (United States)

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  4. RepSox improves viability and regulates gene expression in rhesus monkey-pig interspecies cloned embryos.

    Science.gov (United States)

    Zhu, Hai-Ying; Jin, Long; Guo, Qing; Luo, Zhao-Bo; Li, Xiao-Chen; Zhang, Yu-Chen; Xing, Xiao-Xu; Xuan, Mei-Fu; Zhang, Guang-Lei; Luo, Qi-Rong; Wang, Jun-Xia; Cui, Cheng-Du; Li, Wen-Xue; Cui, Zheng-Yun; Yin, Xi-Jun; Kang, Jin-Dan

    2017-05-01

    To investigate the effect of the small molecule, RepSox, on the expression of developmentally important genes and the pre-implantation development of rhesus monkey-pig interspecies somatic cell nuclear transfer (iSCNT) embryos. Rhesus monkey cells expressing the monomeric red fluorescent protein 1 which have a normal (42) chromosome complement, were used as donor cells to generate iSCNT embryos. RepSox increased the expression levels of the pluripotency-related genes, Oct4 and Nanog (p  0.05), this was not significant. RepSox can improve the developmental potential of rhesus monkey-pig iSCNT embryos by regulating the expression of pluripotency-related genes.

  5. Neurotoxic response of infant monkeys to methylmercury.

    Science.gov (United States)

    Willes, R F; Truelove, J F; Nera, E A

    1978-02-01

    Four infant monkeys were dosed orally with 500 microgram Hg/kg body wt./day /as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28--29 days of treatment; the blood Hg levels were 8.0--9.4 microgram Hg/g blood. Dosing was terminated at 28--29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35--43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver (55.8 +/- 3.2 microgram Hg/g) followed by occipital cortex (35.6 +/- 4.8 microgram Hg/g) renal cortex (32.8 +/- 1.6 microgram Hg/g). The frontal and temporal cortices had 27.0 +/- 3.4 and 29.6 +/- 4.9 microgram Hg/g respectively while the cerebellar Hg concentration averaged 13.0 +/- 1.5 microgram Hg/g. The mean blood/brain ratio was 0.21 +/- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.

  6. PET studie4s of dopamine D2 receptors in subclinical and clinical hemi-parkinsonism monkeys with 11C-Raclopride

    International Nuclear Information System (INIS)

    Bian Yanzhu; Zhang Jinming; Tian Jiahe; Yao Shulin; Liu Huaijun

    2005-01-01

    Objective: To explore the characters of dopamine D 2 receptors (D 2 R) of subclinical and clinical hemi-parkinsonism monkeys. Methods: Four subclinical hemi-pakinsonism monkeys were developed by given one dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropridine (MPTP) 0.3 mg/kg through fight internal carotid artery. Two clinical hemi-pakinsonism monkeys were developed by given 2 doses of MPTP 0.7 mg/kg through right internal carotid artery and the 2 doses were 4 weeks apart. 11 C-Raclopride was synthesized as an imaging agent of D 2 R. Four normal, 4 subclinical and 2 clinical hemi-parkinsonism monkeys underwent 11 C-Raclopride D 2 R PET, and the striatum D 2 R function was evaluated by region of interest (ROI) technique. Results: Symmetric striatal uptake was observed in normal and subclinical hemi-parkinsonism monkeys, the radioactivity ratios of striatum/cerebellum were 5.00±0.74, 5.04±0.72, respectively (t=1.016, P>0.05). There was a significant increase in 11 C-Raclopride binding in the fight striatum (lesioned side) of the two clinical hemi-pakinsonism monkeys; up-regulation of leisoned side striatum D 2 R was found; compared to the left sides, the radioactivity ratios of striatum cerebellum of right sides (lesioned sides) of the two monkeys were increased by 19.69%, 22.68%, respectively. Conclusions: 11 C-Raclopride was successfully synthesized as a D 2 R PET agent. The striatum D 2 R function was of no evident changes in subclinical hemi-parkinsonism monkeys. The striatum 132 R function was upregulated in lesioned side in clinical hemi-parkinsonism monkeys. (authors)

  7. Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection

    OpenAIRE

    Campbell, Jennifer H.; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J.; Tse, Samantha; Miller, Andrew D.; González, R. Gilberto; Salemi, Marco; Burdo, Tricia H.; Williams, Kenneth C.

    2014-01-01

    Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages a...

  8. Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Turchi, Janita; Saunders, Richard C; Mishkin, Mortimer

    2005-02-08

    Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition.

  9. R-warfarin clearances from plasma associated with polymorphic cytochrome P450 2C19 and simulated by individual physiologically based pharmacokinetic models for 11 cynomolgus monkeys.

    Science.gov (United States)

    Utoh, Masahiro; Kusama, Takashi; Miura, Tomonori; Mitsui, Marina; Kawano, Mirai; Hirano, Takahiro; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2018-02-01

    1. Cynomolgus monkey cytochrome P450 2C19 (formerly known as P450 2C75), homologous to human P450 2C19, has been identified as R-warfarin 7-hydroxylase. In this study, simulations of R-warfarin clearance in individual cynomolgus monkeys genotyped for P450 2C19 p.[(Phe100Asn; Ala103Val; Ile112Leu)] were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling. 2. Pharmacokinetic parameters and absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearances for individual PBPK models were estimated for eleven cynomolgus monkeys. 3. One-way ANOVA revealed significant effects of the genotype (p warfarin among the homozygous mutant, heterozygous mutant, and wild-type groups. R-Warfarin clearances in individual cynomolgus monkeys genotyped for P450 2C19 were simulated by simplified PBPK modeling. The modeled hepatic intrinsic clearances were significantly associated with the P450 2C19 genotypes. The liver microsomal elimination rates of R-warfarin for individual animals after in vivo administration showed significant reductions associated with the genotype (p warfarin and related medicines associated with polymorphic P450 2C19 in individual cynomolgus monkeys, thereby facilitating calculation of the fraction of hepatic clearance.

  10. Sichuan Snub-Nosed Monkeys (Rhinopithecus roxellana) Consume Cicadas in the Qinling Mountains, China.

    Science.gov (United States)

    Yang, Bin; Zhang, Peng; Garber, Paul A; Hedley, Richard; Li, Baoguo

    2016-01-01

    There is limited information on insectivory in folivorous primates. Here, we report that wild Sichuan snub-nosed monkeys (Rhinopithecus roxellana) consume cicadas (Karenia caelatata) in the Qinling Mountains of China. Our research suggests that snub-nosed monkeys expand their diet and prey on cicadas during summer and early autumn, possibly in response to increased availability of these insects and their relatively high protein and fat content relative to leaves. © 2016 S. Karger AG, Basel.

  11. Spermatogenesis in adult rhesus monkeys following irradiation with X-rays or fission neutrons

    International Nuclear Information System (INIS)

    Rooij, D.G. de; Sonneveld, P.; Bekkum, D.W. van

    A group of male rhesus monkeys was exposed to total body irradiation followed by autologous bone marrow transplantation. The animals were irradiated in the period between 1965 and 1976 and received a dose of 8.5 Gy of X-rays (300 KVP) or 3.6 Gy of 1 MeV fission neutrons. Of this group, a total of 11 male monkeys proved to be evaluable for studying the effects of irradiation on spermatogenesis. (Auth.)

  12. Autoprocessing of Mason-Pfizer monkey virus protease

    Czech Academy of Sciences Publication Activity Database

    Bauerová, Helena; Rumlová, Michaela; Hunter, E.; Ruml, T.; Pichová, Iva

    2001-01-01

    Roč. 77, č. 2 (2001), s. 131-133 ISSN 0168-1702 R&D Projects: GA ČR GA203/00/1241; GA AV ČR IAA4055904 Grant - others:Fogarty International Award(US) TW00050 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry Impact factor: 1.806, year: 2001

  13. Two distinct variants of simian foamy virus in naturally infected mandrills (Mandrillus sphinx and cross-species transmission to humans

    Directory of Open Access Journals (Sweden)

    Marx Preston

    2010-12-01

    Full Text Available Abstract Background Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1 has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage of another simian retrovirus, simian foamy virus (SFV, from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans. Results We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot and molecular (nested PCR of the integrase region in the polymerase gene assays. Seropositivity for SFV was found in 70/84 (83% captive and 9/15 (60% wild-caught mandrills and in 2/20 (10% humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. Conclusion Our results show a high

  14. Two distinct variants of simian foamy virus in naturally infected mandrills (Mandrillus sphinx) and cross-species transmission to humans.

    Science.gov (United States)

    Mouinga-Ondémé, Augustin; Betsem, Edouard; Caron, Mélanie; Makuwa, Maria; Sallé, Bettina; Renault, Noemie; Saib, Ali; Telfer, Paul; Marx, Preston; Gessain, Antoine; Kazanji, Mirdad

    2010-12-14

    Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1) has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage of another simian retrovirus, simian foamy virus (SFV), from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans. We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon) and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot) and molecular (nested PCR of the integrase region in the polymerase gene) assays. Seropositivity for SFV was found in 70/84 (83%) captive and 9/15 (60%) wild-caught mandrills and in 2/20 (10%) humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time. Our results show a high prevalence of SFV infection in a semi-free-ranging colony

  15. Investigations of rhesus monkey video-task performance: evidence for enrichment

    Science.gov (United States)

    Washburn, D. A.; Rumbaugh, D. M.

    1992-01-01

    We have developed the Language Research Center's Computerized Test System (LRC-CTS) for psychological research. Basically, the LRC-CTS is a battery of software tasks--computerized versions of many of the classic testing paradigms of cognitive and comparative psychology--and the hardware required to administer them. An XT- or 386-compatible computer is connected to a color monitor, onto which computer-generated stimuli are presented. Sound feedback is delivered through an external speaker/amplifier, and a joystick is used as an input device. The animals reach through the mesh of their home cages to manipulate the joystick, which causes isomorphic movements of a cursor on the screen thereby allowing animals to respond according to the varied demands of the tasks. Correct responses are rewarded with a fruit-flavored chow pellet. Using this technology, we have trained and tested rhesus monkeys, a variety of apes, human adults, and normally developing or mentally retarded human children. Other labs using the LRC-CTS are beginning to report encouraging results with other monkey species as well. From this research, a number of interesting and important psychological findings have resulted. In the present paper, however, evidence will be reviewed which suggests that the LRC-CTS is an effective means of providing environmental enrichment to singly housed rhesus monkeys.

  16. Working and waiting for better rewards: self-control in two monkey species (Cebus apella and Macaca mulatta).

    Science.gov (United States)

    Evans, Theodore A; Perdue, Bonnie M; Parrish, Audrey E; Beran, Michael J

    2014-03-01

    Self-control is typically defined as choosing a greater, delayed reward over a lesser, more immediate reward. However, in nature, there are other costs besides delay associated with obtaining the greatest outcome including increased effort, potential punishment, and low probability of reward. Effort is an interesting case because it sometimes impairs self-control, by acting as an additional cost, and at other times facilitates self-control, by distracting one from impulsive options. Additionally, different species may perform differently in effortful self-control tasks, based on their natural ecology. To gain insight into these aspects of self-control behavior, we examined capuchin monkeys' and rhesus monkeys' self-control in separate working and waiting choice tasks. We hypothesized that capuchins would show greater self-control in the working task, given their naturally higher activity level, whereas rhesus would perform similarly in both tasks. Rhesus performed as predicted, whereas contrary to our hypothesis, capuchins exhibited lesser performance in the working task. Nonetheless, these results may still stem from inherent species differences interacting with details of the methodology. Capuchins, being highly energetic and social monkeys, may have divided their energy and attention between the working task and other elements of the test environment such as visible group mates or manipulanda. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Development, validation, and application of ELISA for detection of anti-HD105 antibodies in pre-clinical safety evaluation using monkeys.

    Science.gov (United States)

    Choi, Woo Hyuck; Jo, Hye Ryun; Jeon, Eun-Jeong; Youm, So-Young; Jeon, Jang Su; Son, Yong-Gyu; You, Weon-Kyoo; Koh, Woo Suk; Lee, Sang Hoon; Kim, Sang Kyum

    2016-11-30

    Unwanted immunogenicity of protein therapeutics can result in severe side effects and should be assessed in animals before applying the treatment to humans. Monkeys are the most relevant choice for pre-clinical toxicity testing of antibody-based therapeutics. To assess the immunogenicity of HD105, a novel antibody therapeutic that targets both vascular endothelial growth factor and Delta-like-ligand 4, a bridging enzyme-linked immunosorbent assay was developed as an anti-drug antibody (ADA) assay and validated for use in pre-clinical studies using non-human primates. This method was found to have suitable assay sensitivity, intra- and inter-assay precision, confirmation, drug tolerance, recovery, and sample stability for measuring ADA in monkey serum samples. The results showed that ADA elevation occurred following repeated doses of HD105, and that ADA production was negatively associated with serum HD105 concentration. These results suggest that intravenous administration of HD105 induces production of ADA in monkeys and that the detection of ADA may be negatively influenced by free HD105 in serum. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.

    Directory of Open Access Journals (Sweden)

    Misako Yoneda

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G. Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi. Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.

  19. Detection of circulating Mycobacterium tuberculosis-specific DNA by droplet digital PCR for vaccine evaluation in challenged monkeys and TB diagnosis.

    Science.gov (United States)

    Song, Neng; Tan, Yang; Zhang, Lingyun; Luo, Wei; Guan, Qing; Yan, Ming-Zhe; Zuo, Ruiqi; Liu, Weixiang; Luo, Feng-Ling; Zhang, Xiao-Lian

    2018-04-24

    Mycobacterium tuberculosis (M. tb) is emerging as a more serious pathogen due to the increased multidrug-resistant TB and co-infection of human immunodeficiency virus (HIV). The development of an effective and sensitive detection method is urgently needed for bacterial load evaluation in vaccine development, early TB diagnosis, and TB treatment. Droplet digital polymerase chain reaction (ddPCR) is a newly developed sensitive PCR method for the absolute quantification of nucleic acid concentrations. Here, we used ddPCR to quantify the circulating virulent M. tb-specific CFP10 (10-kDa culture filtrate protein, Rv3874) and Rv1768 DNA copy numbers in the blood samples from Bacille Calmette-Guerin (BCG)-vaccinated and/or virulent M. tb H37Rv-challenged rhesus monkeys. We found that ddPCR was more sensitive compared to real-time fluorescence quantitative PCR (qPCR), as the detection limits of CFP10 were 1.2 copies/μl for ddPCR, but 15.8 copies/μl for qPCR. We demonstrated that ddPCR could detect CFP10 and Rv1768 DNA after 3 weeks of infection and at least two weeks earlier than qPCR in M.tb H37Rv-challenged rhesus monkey models. DdPCR could also successfully quantify CFP10 and Rv1768 DNA copy numbers in clinical TB patients' blood samples (active pulmonary TB, extrapulmonary TB (EPTB), and infant TB). To our knowledge, this study is the first to demonstrate that ddPCR is an effective and sensitive method of measuring the circulating CFP10 and Rv1768 DNA for vaccine development, bacterial load evaluation in vivo, and early TB (including EPTB and infant TB) diagnosis as well.

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

    Directory of Open Access Journals (Sweden)

    Marit Kramski

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