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Sample records for cynomolgus macaca fascicularis

  1. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

    Science.gov (United States)

    Yu, Guo-Yun; Mate, Suzanne; Garcia, Karla; Ward, Michael D; Brueggemann, Ernst; Hall, Matthew; Kenny, Tara; Sanchez-Lockhart, Mariano; Lefranc, Marie-Paule; Palacios, Gustavo

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

  2. Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis)

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    Laffins, Michael M; Mellal, Nacera; Almlie, Cynthia L; Regalia, Douglas E

    2017-01-01

    Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations. Infrared measurements were taken 5 cm from the chest and inguinal areas. We evaluated 10 (9 functional devices) sedated cynomolgus macaques (5 male, 5 female) implanted with telemetry units in a muscular pouch between the internal and external abdominal oblique muscles. We determined that the mean body temperature acquired by using telemetry did not differ from either the mean of inguinal and chest infrared measurements but did differ from the mean of temperature obtained rectally. In addition, the mean rectal temperature differed from the mean of the inguinal reading but not the mean of the chest temperature. The results confirm our hypothesis that the infrared thermometer can be used to replace standard rectal thermometry. PMID:28905720

  3. Probing around implants and teeth with healthy or inflamed peri-implant mucosa/gingival. A histologic comparison in cynomolgus monkeys. (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Schou, Søren; Holmstrup, Palle; Stoltze, K.

    2002-01-01

    Osseointegrated oral implants; teeth; phathology; peri-implant mucositis; gingivitis; peri-implantitis; periodontitis; diagnosis; probing depth; non-human primates; cynomolgus monkeys: Macaca fascicularis......Osseointegrated oral implants; teeth; phathology; peri-implant mucositis; gingivitis; peri-implantitis; periodontitis; diagnosis; probing depth; non-human primates; cynomolgus monkeys: Macaca fascicularis...

  4. Chronic lymphocytic thyroiditis in a cynomolgus macaque (Macaca fascicularis).

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    Guzman, Roberto E; Radi, Zaher A

    2007-02-01

    Chronic lymphocytic thyroiditis characterized by multifocal follicular lymphoid cell infiltrates with germinal centers, thyroid acinar atrophy and pituitary cell hyperplasia/hypertrophy of the adenohypophysis was detected in a vehicle control, 4-year-old female Cynomolgus macaque in a routine toxicology study. Lymphoid cells of germinal centers were positive for the B-cell marker CD20 by immunohistochemistry (IHC), while remaining lymphocytes were positive for the T-cell marker CD3. Hypertrophied/hyperplastic pituitary cells were positive for thyroid stimulating hormone (TSH) by IHC, consistent with an adaptive response due to removal of hormonal negative feedback from the diseased thyroid gland. Features of this case are similar to chronic lymphocytic thyroiditis in humans, an autoimmune disorder also known as Hashimoto's disease. Chronic lymphocytic thyroiditis with compensatory pituitary changes may occur spontaneously in young, clinically normal cynomolgus macaques and its presence in drug treated animals should be interpreted with caution.

  5. Allele frequency of antiretroviral host factor TRIMCyp in wild-caught cynomolgus macaques (Macaca fascicularis)

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    Saito, Akatsuki; Kawamoto, Yoshi; Higashino, Atsunori; Yoshida, Tomoyuki; Ikoma, Tomoko; Suzaki, Yuriko; Ami, Yasushi; Shioda, Tatsuo; Nakayama, Emi E.; Akari, Hirofumi

    2012-01-01

    A recent study showed that the frequency of an antiretroviral factor TRIM5 gene-derived isoform, TRIMCyp, in cynomolgus macaques (Macaca fascicularis) varies widely according to the particular habitat examined. However, whether the findings actually reflect the prevalence of TRIMCyp in wild cynomolgus macaques is still uncertain because the previous data were obtained with captive monkeys in breeding and rearing facilities. Here, we characterized the TRIM5 gene in cynomolgus macaques captured in the wild, and found that the frequency of the TRIMCyp allele was comparable to those in captive monkeys. This suggests that the previous results with captive monkeys do indeed reflect the natural allele frequency and that breeding and rearing facilities may not affect the frequency of TRIM5 alleles. Interestingly, the prevalence of a minor haplotype of TRIMCyp in wild macaques from the Philippines was significantly lower than in captive ones, suggesting that it is advantageous for wild monkeys to possess the major haplotype of TRIMCyp. Overall, our results add to our understanding of the geographic and genetic prevalence of cynomolgus macaque TRIMCyp. PMID:22969754

  6. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

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    Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

    2011-05-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

  7. A natural model of behavioral depression in postpartum adult female cynomolgus monkeys (Macaca fascicularis).

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    Chu, Xun-Xun; Dominic Rizak, Joshua; Yang, Shang-Chuan; Wang, Jian-Hong; Ma, Yuan-Ye; Hu, Xin-Tian

    2014-05-01

    Postpartum depression (PPD) is a modified form of major depressive disorders (MDD) that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys (Macaca fascicularis) living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum (BDP) as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups: A BDP group (n=6), which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group (n=4). The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction-similar to humans-as well as much greater homology to humans

  8. Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

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    Vickers Mark H

    2011-10-01

    Full Text Available Abstract Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile to those of lower birth weight (5-25th centile and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk.

  9. Blood genomic profiles of exposures to Venezuelan equine encephalitis in Cynomolgus macaques (Macaca fascicularis

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    Hammamieh Rasha

    2007-08-01

    Full Text Available Abstract Background Lymphocytes provide invaluable whistle blowers of changes due to infections. We use the information registered by these cells using their mRNAs as they encounter the pathogen to develop patterns of expression that correspond to that specific pathogen. Venezuelan equine encephalitis (VEE is a mosquito-borne viral disease characterized by fever and one or more of the following: severe headache, back pain, myalgias, prostration, chills, nausea, vomiting, weakness and other flu-like symptoms. Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment. Results We have been carrying out gene expression analysis of PBMC exposed to VEEV to extract signatures and diagnostic markers of early exposure to be used in non invasive blood analysis methods. In this study, we used high throughput gene expression analysis to identify markers of early and late exposures to VEEV in vivo in Cynomolgus macaques (Macaca fascicularis. We carried out cDNA microarrays and real time PCR on blood samples obtained from the NHP model resulting in a panel of host genes that are altered in response to VEEV. Conclusion Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment.

  10. Experimental oral toxicity of domoic acid in cynomolgus monkeys (Macaca fascicularis) and rats. Preliminary investigations.

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    Tryphonas, L; Truelove, J; Todd, E; Nera, E; Iverson, F

    1990-10-01

    A recent outbreak of marine food poisoning in humans was attributed to the consumption of blue mussels (Mytilus edulis L.) contaminated with domoic acid (DA) that was produced by the diatom Nitzschia pungens. The clinical and morphological effects of single oral doses of extracts of mussels contaminated with DA or of DA isolated from toxic mussels were investigated in small groups (one to six) of cynomolgus monkeys (Macaca fascicularis; 0.5-10 mg DA/kg body weight) and of Sprague-Dawley rats (60 to 80 mg DA/kg body weight). Control animals were either given saline or were not treated. To test whether monosodium glutamate, present in the food consumed by some affected humans, and dimethylsulphoxide, suspected of being present in the plankton, enhanced the response, monosodium glutamate (at 0.25% of mussel extract bolus) or dimethylsulphoxide (at 1 g per bolus) were co-administered to two (one each) of the DA-treated monkeys. DA-treated monkeys developed transient excitation characterized by vomiting. DA-treated rats showed withdrawal followed by hyperexcitation and death (in one case). Mild to moderate central nervous system lesions consistent with neuroexcitation were present in both monkeys and rats. The addition of monosodium glutamate and dimethylsulphoxide had no significant effect on the appearance and severity of central nervous system clinical signs and lesions. The wide variations in the response of test animals to orally administered DA were attributed to the protective effect of vomiting, and to suspected incomplete or slow gastro-intestinal absorption of the toxic agent. The results reinforce the view that DA is an emetic and that under appropriate conditions may also inflict excitotoxic central nervous system damage.

  11. Maxillary nerve compression in cynomolgus monkey Macaca fascicularis: altered somatic sensation and peripheral nerve firing

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    Guo Ning

    2012-12-01

    Full Text Available Abstract Background Trigeminal nerve is a major source of the sensory input of the face, and trigeminal neuropathology models have been reported in rodents with injury to branches of the maxillary or mandibular division of the trigeminal nerve. Non-human primates are neuroanatomically more closely related to human than rodents; however, nerve injury studies in non-human primates are limited. Results We describe here a nerve injury model of maxillary nerve compression (MNC in the cynomolgus macaque monkey, Macaca fascicularis, and the initial characterization of the consequences of damage to this trigeminal nerve branch. The nerve injury from the compression appeared to be mild, as we did not observe overt changes in home-cage behavior in the monkeys. When mechanical stimulation was applied to the facial area, monkeys with MNC displayed increased mechanical sensitivity, as the avoidance response scores were lower than those from the control animals. Such a change in mechanical sensitivity appeared to be somewhat bilateral, as the contralateral side also showed increased mechanical sensitivity, although the change on the ipsilateral side was more robust. Multiple-unit recording of the maxillary nerve showed a general pattern of increasing responsiveness to escalating force in mechanical stimulation on the contralateral side. Ipsilateral side of the maxillary nerve showed a lack of responsiveness to escalating force in mechanical stimulation, possibly reflecting a maximum stimulation threshold effect from sensitized nerve due to MNC injury. Conclusions These results suggest that MNC may produce increased sensitivity of the ipsilateral maxillary nerve, and that this model may serve as a non-human primate model to evaluate the effect of injury to trigeminal nerve branches.

  12. Antimicrobial resistance in Campylobacter coli and Campylobacter jejuni in cynomolgus monkeys (Macaca fascicularis) and eradication regimens.

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    Koga, Tetsufumi; Aoki, Wataru; Mizuno, Takashi; Wakazono, Kuniko; Ohno, Junki; Nakai, Tsunehiro; Nomiya, Takao; Fujii, Miki; Fusegawa, Keiichi; Kinoshita, Kazuya; Hamada, Takakazu; Ikeda, Yoshinori

    2017-02-01

    Campylobacter spp. are zoonotic pathogens, however, knowledge about their presence and antimicrobial resistance in nonhuman primates is limited. Our animal facility purchased cynomolgus monkeys (Macaca fascicularis) from various Asian countries: China, Cambodia, Indonesia, the Philippines, and Vietnam. Colonization by Campylobacter spp. was investigated in 238 of the monkeys from 2009 to 2012 and antimicrobial susceptibility testing was carried out for these isolates. Furthermore, we eradicated these pathogens from these monkeys. Campylobacter spp. were isolated from 47 monkeys from three specific countries: China, Cambodia, and Indonesia, with respective isolation rates of 15%, 36%, and 67%. Two monkeys, which were each infected with Campylobacter jejuni and Campylobacter coli, showed clinical symptoms of diarrhea and bloody feces. In total, 41 isolates of C. coli and 17 isolates of C. jejuni were detected. Antimicrobial susceptibility varied: in the monkeys from China, erythromycin (ERY)-, tetracycline (TET)-, and ciprofloxacin-resistant C. coli, in the monkeys from Cambodia, amoxicillin-intermediate, TET- and ciprofloxacin-resistant C. coli and amoxicillin- and ciprofloxacin-resistant C. jejuni, and in the monkeys from Indonesia, ciprofloxacin-resistant C. coli and TET- and ciprofloxacin-resistant C. jejuni were common (>75%). Multiresistant isolates of C. coli were found in monkeys from all countries and multiresistant isolates of C. jejuni were found in monkeys from Indonesia. The eradication rate with azithromycin was comparable to that with gentamicin (GEN) by oral administration, and was higher than those with amoxicillin-clavulanic acid (AMC) and chloramphenicol (CHL). From the perspective of zoonosis, we should acknowledge multiresistant Campylobacter spp. isolated from the monkeys as a serious warning. Copyright © 2015. Published by Elsevier B.V.

  13. Effects elicited by toxaphene in the cynomolgus monkey (Macaca fascicularis): a pilot study.

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    Bryce, F; Iverson, F; Andrews, P; Barker, M; Cherry, W; Mueller, R; Pulido, O; Hayward, S; Fernie, S; Arnold, D L

    2001-12-01

    Toxaphene, which was added to glycerol/corn oil, was administered at a level of 1 mg/kg body weight/day in gelatin capsules to four healthy young adult cynomolgus (Macaca fascicularis) monkeys for 52 weeks. Four control monkeys ingested capsules containing only glycerol/corn oil. Each group had two males and two females. On a daily basis, each monkey's feed and water consumption was determined, its health was monitored and the females were swabbed to evaluate menstrual status. On a weekly basis, each monkey's body weight was determined and a detailed clinical evaluation was performed. At 4-week intervals, blood samples were taken for serum biochemistry, haematology and toxaphene analysis. Also, a local anaesthetic was administered to the nuchal fat pad area of each monkey, and adipose samples were obtained for toxaphene analysis. 1 day prior to the biopsies, a 24-h urine and faecal collection was obtained for toxaphene analysis. After 34 weeks of treatment, the immune system of the monkeys was evaluated. After 52 weeks of dosing, all treated and two control animals were necropsied. Liver samples were obtained and microsomal fractions were prepared immediately. A portion of liver and kidney was taken for toxaphene analysis. All of the major internal organs were weighed and bone marrow evaluations were conducted. Organ and tissue samples were fixed in 10% formalin and processed for light microscopy. There was no effect of treatment on body weight gain, feed consumption, water consumption or haematological parameters. Two major clinical findings were inflammation and/or enlargement of the tarsal gland and impacted diverticulae in the upper and lower eye lids. At necropsy, the relative spleen and thymus weights were greater for the treated monkeys than the controls. Toxaphene administration produced an increase in metabolism of aminopyrene, methoxyresorufin and ethoxyresorufin, three substrates that are altered specifically by cytochrome P450-based hepatic

  14. Stimulus-Food Pairings Produce Stimulus-Directed Touch Screen Responding in Cynomolgus Monkeys ("Macaca Fascicularis") with or without a Positive Response Contingency

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    Bullock, Christopher E.; Myers, Todd M.

    2009-01-01

    Acquisition and maintenance of touch-screen responding was examined in naive cynomolgus monkeys ("Macaca fascicularis") under automaintenance and classical conditioning arrangements. In the first condition of Experiment 1, we compared acquisition of screen touching to a randomly positioned stimulus (a gray square) that was either stationary or…

  15. Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication.

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    Amado, Luciane A; Marchevsky, Renato S; de Paula, Vanessa S; Hooper, Cleber; Freire, Marcos da S; Gaspar, Ana Maria C; Pinto, Marcelo A

    2010-02-01

    This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi). Liver samples, submandibular salivary gland, mesenteric lymph node and tonsils were removed for virological and pathological evaluation. Immunofluorescence analyses on liver and salivary gland sections using confocal laser scanning microscopy revealed the presence of HAV antigen (HAV Ag). The presence of HAV genome was monitored by real-time PCR. The HAV RNA was detected at 7 days postinoculation (dpi), concomitantly in serum, saliva and faeces. The highest HAV viral load was observed in faeces at 15 dpi (10(5) copies/ml), followed by serum viral load of 10(4) copies/ml at 20 dpi and saliva viral load of 10(3 )copies/ml at 7 dpi. The animals showed first histological and biochemical signs of hepatitis at 15 dpi. The HAV antigen (Ag) was present from day 7 until day 60 pi in the liver and salivary glands. The HAV replicative intermediate was also detected in the liver (4.5 x 10(4) copies/mg), salivary glands (1.9 x 10(3) copies/mg), tonsils (4.2 x 10(1) copies/mg) and lymph nodes (3.4 x 10(1) copies/mg). Our data demonstrated that the salivary gland as an extrahepatic site of early HAV replication could create a potential risk of saliva transmitted infection. In addition, the cynomolgus monkey was confirmed as a suitable model to study the pathogenesis of HAV human infection.

  16. Whole-genome sequencing of six Mauritian Cynomolgus macaques (Macaca fascicularis) reveals a genome-wide pattern of polymorphisms under extreme population bottleneck.

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    Osada, Naoki; Hettiarachchi, Nilmini; Adeyemi Babarinde, Isaac; Saitou, Naruya; Blancher, Antoine

    2015-03-23

    Cynomolgus macaques (Macaca fascicularis) were introduced to the island of Mauritius by humans around the 16th century. The unique demographic history of the Mauritian cynomolgus macaques provides the opportunity to not only examine the genetic background of well-established nonhuman primates for biomedical research but also understand the effect of an extreme population bottleneck on the pattern of polymorphisms in genomes. We sequenced the whole genomes of six Mauritian cynomolgus macaques and obtained an average of 20-fold coverage of the genome sequences for each individual. The overall level of nucleotide diversity was 23% smaller than that of the Malaysian cynomolgus macaques, and a reduction of low-frequency polymorphisms was observed. In addition, we also confirmed that the Mauritian cynomolgus macaques were genetically closer to a representative of the Malaysian population than to a representative of the Indochinese population. Excess of nonsynonymous polymorphisms in low frequency, which has been observed in many other species, was not very strong in the Mauritian samples, and the proportion of heterozygous nonsynonymous polymorphisms relative to synonymous polymorphisms is higher within individuals in Mauritian than Malaysian cynomolgus macaques. Those patterns indicate that the extreme population bottleneck made purifying selection overwhelmed by the power of genetic drift in the population. Finally, we estimated the number of founding individuals by using the genome-wide site frequency spectrum of the six samples. Assuming a simple demographic scenario with a single bottleneck followed by exponential growth, the estimated number of founders (∼20 individuals) is largely consistent with previous estimates.

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

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    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

  18. Survey of prevalence of overweight body condition in laboratory-housed cynomolgus macaques (Macaca fascicularis).

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    Bauer, Sharon A; Leslie, Ken E; Pearl, David L; Fournier, Jocelyn; Turner, Patricia V

    2010-07-01

    Excessive weight gain has been reported to occur in captive cynomolgus macaques with little to no change in diet. Overweight body condition can result in development of hyperglycemia and type 2 diabetes and should be avoided. The purpose of this survey was to assess the prevalence of overweight cynomolgus macaques in North American research facilities, including breeding colonies and short-term and long-term facilities, and to describe current methods used to assess body condition. The survey consisted of 51 questions covering animal population demographics, body weight and body condition scoring, feeding, and behavior. Voluntary participants included veterinarians and animal care managers. Respondents from 13 facilities completed the survey, and information was collected on 17,500 cynomolgus macaques. The majority of surveyed facilities housed juvenile and young adult macaques. The reported prevalence of overweight (greater than 10% of ideal body weight) animals ranged between 0% and 20% and reportedly was more frequent in animals younger than 10 y. Most facilities had weight reduction strategies in place. Despite these programs, a significant proportion of animals were reported as being overweight. The results of this survey demonstrate that most North American facilities housing cynomolgus macaques recognize the importance of tracking body condition regularly. However, implementing effective weight reduction programs may be difficult in captive housing environments. Because of the potential for adverse health effects, facilities should have a means of regularly tracking body weight as well as an action plan for managing overweight animals.

  19. Physiological and behavioural stress responses in cynomolgus macaques (Macaca fascicularis) to noise associated with construction work

    DEFF Research Database (Denmark)

    Westlund, K; Fernström, A-L; Wergård, E-M

    2012-01-01

    The aim of the present study was to evaluate the behavioural and physiological responses to environmental disturbances (live and recorded dynamite explosions) in laboratory non-human primates in preparation for a future tunnel construction underneath our animal facility. In a pilot study (A) on 20...... detonations on the behaviour and CICM in 16 M. fascicularis. In the latter study we introduced a predictive signal, serving as a conditional stimulus, to half of the animals. We found no significant effects of the noise in the Signal group; while the Control groups' CICM values were affected. The behaviour...... was largely unaffected in the two groups. It was decided not to introduce a research moratorium on biomedical research planned to be conducted during the future tunnel construction, and that a conditional stimulus ('warning signal') will be used....

  20. Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

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    Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

    2012-06-01

    Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

  1. Normal Anatomy, Histology, and Spontaneous Pathology of the Nasal Cavity of the Cynomolgus Monkey (Macaca fascicularis).

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    Chamanza, Ronnie; Taylor, Ian; Gregori, Michela; Hill, Colin; Swan, Mark; Goodchild, Joel; Goodchild, Kane; Schofield, Jane; Aldous, Mark; Mowat, Vasanthi

    2016-07-01

    The evaluation of inhalation studies in monkeys is often hampered by the scarcity of published information on the relevant nasal anatomy and pathology. We examined nasal cavities of 114 control cynomolgus monkeys from 11 inhalation studies evaluated 2008 to 2013, in order to characterize and document the anatomic features and spontaneous pathology. Compared to other laboratory animals, the cynomolgus monkey has a relatively simple nose with 2 unbranched, dorsoventrally stacked turbinates, large maxillary sinuses, and a nasal septum that continues into the nasopharynx. The vomeronasal organ is absent, but nasopalatine ducts are present. Microscopically, the nasal epithelium is thicker than that in rodents, and the respiratory (RE) and transitional epithelium (TE) rest on a thick basal lamina. Generally, squamous epithelia and TE line the vestibule, RE, the main chamber and nasopharynx, olfactory epithelium, a small caudodorsal region, while TE is observed intermittently along the passages. Relatively high incidences of spontaneous pathology findings, some resembling induced lesions, were observed and included inflammation, luminal exudate, scabs, squamous and respiratory metaplasia or hyperplasia, mucous cell hyperplasia/metaplasia, and olfactory degeneration. Regions of epithelial transition were the most affected. This information is considered helpful in the histopathology evaluation and interpretation of inhalation studies in monkeys.

  2. Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis) infected with group A Streptococcus.

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    Olsen, Randall J; Ashraf, Madiha; Gonulal, Vedia E; Ayeras, Ara A; Cantu, Concepcion; Shea, Patrick R; Carroll, Ronan K; Humbird, Tammy; Greaver, Jamieson L; Swain, Jody L; Chang, Ellen; Ragasa, Willie; Jenkins, Leslie; Lally, Kevin P; Blasdel, Terry; Cagle, Philip; Musser, James M

    2010-12-01

    Group A Streptococcus (GAS), a human-specific pathogen, is best known for causing pharyngitis ("strep-throat") and necrotizing fasciitis ("flesh-eating disease"). However, the organism is also an uncommon but important cause of community-acquired bronchopneumonia, an infection with an exceptionally high mortality rate. Inasmuch as little is known about the molecular pathogenesis of GAS lower respiratory tract infection, we sought to develop a relevant human infection model. Nine cynomolgus macaques were infected by intra-bronchial instillation of either sterile saline or GAS (10(5) or 10(7) CFU). Animals were continuously monitored and sacrificed at five days post-inoculation. Serial bronchial alveolar lavage specimens and tissues collected at necropsy were used for histologic and immunohistochemical examination, quantitative microbial culture, lung and blood biomarker analysis, and in vivo GAS gene expression studies. The lower respiratory tract disease observed in cynomolgus macaques mimicked the clinical and pathological features of severe GAS bronchopneumonia in humans. This new monkey model will be useful for testing hypotheses bearing on the molecular pathogenesis of GAS in the lower respiratory tract.

  3. Cryopreservation of cynomolgus monkey (Macaca fascicularis) spermatozoa in a chemically defined extender

    Institute of Scientific and Technical Information of China (English)

    Ya-Hui Li; Ke-Jun Cai; Lei Su; Mo Guan; Xie-Chao He; Hong Wang; Andras Kovacs; Wei-Zhi Ji

    2005-01-01

    Aim: To establish a method for cynomolgus monkey sperm cryopreservation in a chemically defined extender.Methods: Semen samples were collected by electro-ejaculation from four sexually mature male cynomolgus monkeys.The spermatozoa were frozen in straws by liquid nitrogen vapor using egg-yolk-free Tes-Tris (mTTE) synthetic extender and glycerol as cryoprotectant. The effects of glycerol concentration (1%, 3%, 5%, 10% and 15% [v/v])and its equilibration time (10 min, 30 min, 60 min and 90 min) on post-thaw spermatozoa were examined by sperm motility and sperm head membrane integrity. Results: The post-thaw motility and head membrane integrity of spermatozoa were significantly higher (P < 0.05) for 5% glycerol (42.95 ± 2.55 and 50.39 ± 2.42, respectively) than those of the other groups (1%: 19.19 ± 3.22 and 24.84 ± 3.64; 3%: 34.23 ± 3.43 and 41.37 ± 3.42; 10%:15.68 ± 2.36 and 21.39 ± 3.14; 15%: 7.47 ± 1.44 and 12.90 ± 2.18). The parameters for 30 min equilibration (42.95 ± 2.55 and 50.39 ± 2.42) were better (P < 0.05) than those of the other groups (10 min: 31.33 ± 3.06 and 38.98 ± 3.31; 60 min: 32.49 ± 3.86 and 40.01 ± 4.18; 90 min: 31.16 ± 3.66 and 38.30 ± 3.78). Five percent glycerol and 30 min equilibration yielded the highest post-thaw sperm motility and head membrane integrity. Conclusion:Cynomolgus monkey spermatozoa can be successfully cryopreserved in a chemically defined extender, which is related to the concentration and the equilibration time of glycerol.

  4. Spontaneous cerebellar primitive neuroectodermal tumor in a juvenile cynomolgus monkey (Macaca fascicularis).

    Science.gov (United States)

    Mukaratirwa, Sydney; Rogerson, Petrina; Blanco, Ana L; Naylor, Stuart W; Bradley, Alys

    2012-08-01

    A neoplastic mass compressing the left cerebellar hemisphere and hindbrain was observed at trimming in a 3½-year-old male cynomolgus monkey from a control dose group. Microscopically, the neoplastic mass was nonencapsulated, invasive, and showed two morphological patterns. The predominant area consisted of densely packed undifferentiated, polygonal to spindle cells arranged in vague sheets supported by a scant fibrovascular stroma. The other area was less cellular and composed of round neoplastic cells separated by eosinophilic fibrillar material. Immunohistochemical staining for vimentin, synaptophysin, glial fibrillary acidic protein, neuron-specific enolase, neurofilament, and S-100 confirmed the presence of primitive undifferentiated neuroectodermal cells and some cells with neuronal or glial differentiation. On the basis of histopathology and immunohistochemical findings, a diagnosis of cerebellar primitive neuroectodermal tumor with neuronal and glial differentiation was made. Primitive neuroectodermal tumors are rare in animals including nonhuman primates; this is the first published report in this species.

  5. Pedicled Instep Flap and Tibial Nerve Reconstruction in a Cynomolgus Monkey [Macaca fascicularis

    Directory of Open Access Journals (Sweden)

    Ruth Weiss

    2016-01-01

    Full Text Available A male cynomolgus monkey experienced extensive soft tissue trauma to the right caudal calf area. Some weeks after complete healing of the original wounds, the monkey developed a chronic pressure sore on plantar surface of the heel of its right foot. A loss of sensitivity in the sole of the foot was hypothesized. The skin defect was closed by a medial sensate pedicled instep flap followed by counter transplantation of a full thickness graft from the interdigital webspace. The integrity of the tibial nerve was revised and reconstructed by means of the turnover flap technique. Both procedures were successful. This is an uncommon case in an exotic veterinary patient as it demonstrates a reconstructive skin flap procedure for the treatment of a chronic, denervated wound in combination with the successful reconstruction of 2.5 cm gap in the tibial nerve.

  6. Stress-relevant social behaviors of middle-class male cynomolgus monkeys (Macaca fascicularis).

    Science.gov (United States)

    Cui, Ding; Zhou, Yuan

    2015-11-18

    Stress from dominance ranks in human societies, or that of other social animals, especially nonhuman primates, can have negative influences on health. Individuals holding different social status may be burdened with various stress levels. The middle class experiences a special stress situation within the dominance hierarchy due to its position between the higher and lower classes. Behaviorally, questions about where middle-class stress comes from and how individuals adapt to middle-class stress remain poorly understood in nonhuman primates. In the present study, social interactions, including aggression, avoidance, grooming and mounting behaviors, between beta males, as well as among group members holding higher or lower social status, were analyzed in captive male-only cynomolgus monkey groups. We found that aggressive tension from the higher hierarchy members was the main origin of stress for middle-class individuals. However, behaviors such as attacking lower hierarchy members immediately after being the recipient of aggression, as well as increased avoidance, grooming and mounting toward both higher and lower hierarchy members helped alleviate middle-class stress and were particular adaptations to middle-class social status.

  7. Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis

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    Montag Judith

    2011-06-01

    Full Text Available Abstract Background Prion diseases such as bovine spongiform encephalopathies (BSE are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results Cynomolgus macaques (Macaca fasicularis were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2 RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2 Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.

  8. 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...

  9. A critical analysis of the cynomolgus macaque, Macaca fascicularis, as a model to test HIV-1/SIV vaccine efficacy.

    Science.gov (United States)

    Antony, Joseph M; MacDonald, Kelly S

    2015-06-17

    The use of a number of non-rhesus macaque species, but especially cynomolgus macaques as a model for HIV-1 vaccine development has increased in recent years. Cynomolgus macaques have been used in the United Kingdom, Europe, Canada and Australia as a model for HIV vaccine development for many years. Unlike rhesus macaques, cynomolgus macaques infected with SIV show a pattern of disease pathogenesis that more closely resembles that of human HIV-1 infection, exhibiting lower peak and set-point viral loads and slower progression to disease with more typical AIDS defining illnesses. Several advances have been made recently in the use of the cynomolgus macaque SIV challenge model that allow the demonstration of vaccine efficacy using attenuated viruses and vectors that are both viral and non-viral in origin. This review aims to probe the details of various vaccination trials carried out in cynomolgus macaques in the context of our modern understanding of the highly diverse immunogenetics of this species with a view to understanding the species-specific immune correlates of protection and the efficacy of vectors that have been used to design vaccines. Copyright © 2015. Published by Elsevier Ltd.

  10. Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis).

    Science.gov (United States)

    Umeda, Shinsuke; Suzuki, Michihiro T; Okamoto, Haru; Ono, Fumiko; Mizota, Atsushi; Terao, Keiji; Yoshikawa, Yasuhiro; Tanaka, Yasuhiko; Iwata, Takeshi

    2005-10-01

    We have previously reported a cynomolgus monkey (Macaca fascicularis) pedigree with early onset macular degeneration that develops drusen at 2 yr after birth. In this study, the molecular composition of drusen in monkeys affected with late onset and early onset macular degeneration was both characterized. Involvement of anti-retinalautoimmunity in the deposition of drusen and the pathogenesis of the disease was also evaluated. Funduscopic and histological examinations were performed on 278 adult monkeys (mean age=16.94 yr) for late onset macular degeneration. The molecular composition of drusen was analyzed by immunohistochemistry and/or direct proteome analysis using liquid chromatography tandem mass spectroscopy (LC-MS/MS). Anti-retinal autoantibodies in sera were screened in 20 affected and 10 age-matched control monkeys by Western blot techniques. Immunogenic molecules were identified by 2D electrophoresis and LC-MS/MS. Relative antibody titer against each antigen was determined by ELISA in sera from 42 affected (late onset) and 41 normal monkeys. Yellowish-white spots in the macular region were observed in 90 (32%) of the late onset monkeys that were examined. Histological examination demonstrated that drusen or degenerative retinal pigment epithelium (RPE) cells were associated with the pigmentary abnormalities. Drusen in both late and early onset monkeys showed immunoreactivities for apolipoprotein E, amyloid P component, complement component C5, the terminal C5b-9 complement complex, vitronectin, and membrane cofactor protein. LC-MS/MS analyses identified 60 proteins as constituents of drusen, including a number of common components in drusen of human age-related macular degeneration (AMD), such as annexins, crystallins, immunoglobulins, and complement components. Half of the affected monkeys had single or multiple autoantibodies against 38, 40, 50, and 60 kDa retinal proteins. The reacting antigens of 38 and 40 kDa were identified as annexin II and mu

  11. Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

    Science.gov (United States)

    Bell, T M; Shaia, C I; Bunton, T E; Robinson, C G; Wilkinson, E R; Hensley, L E; Cashman, K A

    2015-01-01

    Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection. © The Author(s) 2014.

  12. Superovulatory responses in cynomolgus monkeys (Macaca fascicularis) depend on the interaction between donor status and superovulation method used

    Science.gov (United States)

    KIM, Ji-Su; YOON, Seung-Bin; JEONG, Kang-Jin; SIM, Bo-Woong; CHOI, Seon-A; LEE, Sang-Il; JIN, Yeung Bae; SONG, Bong-Seok; LEE, Sang-Rae; KIM, Sun-Uk; CHANG, Kyu-Tae

    2017-01-01

    The current study was performed to investigate the effect of oocyte donor status, including age and body weight, on metaphase II (MII) oocyte recovery using two superovulation methods in cynomolgus monkeys. The use of Method A [recombinant gonadotrophin (75 IU/kg, 3 ×, 3-day intervals) and human chorionic gonadotropin (hCG)] led to great increases in ovary size and the mean number of MII oocytes retrieved in age- and body-weight-dependent manner; in contrast, both the parameters were similar in Method B [recombinant gonadotrophin (60 IU, twice daily, 6 days), recombinant gonadotropin and recombinant human luteinizing hormone (rhLH) (60 IU, twice daily, 3 days), and hCG]. Importantly, Method A showed maximal MII oocyte recovery rate in > 60-month-old or 4.5–5.0-kg female monkeys, whereas Method B was equally effective regardless of the donor age and body weight. These results indicate that superovulatory responses depend on the interaction between oocyte donor status and the superovulation method used in cynomolgus monkeys. PMID:28070055

  13. Clinical and magnetic resonance imaging features of compressive cervical myelopathy with traumatic intervertebral disc herniation in cynomolgus macaque (Macaca fascicularis)

    Science.gov (United States)

    Choi, Yun-Jung; Park, Hye-Jin; Sohn, Chul-Ho; Jung, Kyeong Cheon; Park, Seong Hoe

    2016-01-01

    Intervertebral disc herniation (IVDH) with nucleus pulposus extrusion, traumatic or not, is a devastating clinical condition accompanied by neurological problems. Here we report a cynomolgus macaque suffering from acute and progressive neurological dysfunction by a blunt trauma due to neck collar, an animal handling device. Tetraplegia, urinary incontinence, decreased proprioception, and imperception of pain were shown on physical and neurological examinations. MRI sagittal T2 weighted sequences revealed an extensive protrusion of disc material between C2 and C3 cervical vertebra, and this protrusion resulted in central stenosis of the spinal cord. Histopathologic findings showed a large number of inflammatory cells infiltrated at sites of spinal cord injury (SCI). This case is the first report of compressive cervical SCI caused by IVDH associated with blunt trauma. PMID:28053621

  14. Construction and Validation of a Systematic Ethogram of Macaca fascicularis in a Free Enclosure

    OpenAIRE

    Fan Xu; Liang Xie; Xin Li; Qi Li; Tao Wang; Yongjia Ji; Fei Kong; Qunlin Zhan; Ke Cheng; Liang Fang; Peng Xie

    2012-01-01

    Behavioral studies in non-human primates have become ideal models for further investigations into advanced cognitive function in humans. To date, there is no systematic ethogram of the cynomolgus monkey (Macaca fascicularis) in a free enclosure. In a field observation of 6012 subjects, 107 distinct behaviors of M. fascicularis were preliminarily described. 83 of these behaviors were then independently validated through a randomized cohort and classified into 12 behavioral categories. 53 of th...

  15. Construction and validation of a systematic ethogram of Macaca fascicularis in a free enclosure.

    Science.gov (United States)

    Xu, Fan; Xie, Liang; Li, Xin; Li, Qi; Wang, Tao; Ji, Yongjia; Kong, Fei; Zhan, Qunlin; Cheng, Ke; Fang, Liang; Xie, Peng

    2012-01-01

    Behavioral studies in non-human primates have become ideal models for further investigations into advanced cognitive function in humans. To date, there is no systematic ethogram of the cynomolgus monkey (Macaca fascicularis) in a free enclosure. In a field observation of 6012 subjects, 107 distinct behaviors of M. fascicularis were preliminarily described. 83 of these behaviors were then independently validated through a randomized cohort and classified into 12 behavioral categories. 53 of these behaviors were then selected to accurately reflect the daily mundane activity of the species in a free enclosure. These findings systematically document the behavior of M. fascicularis in a free enclosure for use in further investigations.

  16. Construction and validation of a systematic ethogram of Macaca fascicularis in a free enclosure.

    Directory of Open Access Journals (Sweden)

    Fan Xu

    Full Text Available Behavioral studies in non-human primates have become ideal models for further investigations into advanced cognitive function in humans. To date, there is no systematic ethogram of the cynomolgus monkey (Macaca fascicularis in a free enclosure. In a field observation of 6012 subjects, 107 distinct behaviors of M. fascicularis were preliminarily described. 83 of these behaviors were then independently validated through a randomized cohort and classified into 12 behavioral categories. 53 of these behaviors were then selected to accurately reflect the daily mundane activity of the species in a free enclosure. These findings systematically document the behavior of M. fascicularis in a free enclosure for use in further investigations.

  17. Correlations between serum levels of beta amyloid, cerebrospinal levels of tau and phospho tau, and delayed response tasks in young and aged cynomolgus monkeys (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Darusman, Huda Shalahudin; Sajuthi, D; Kalliokoski, O

    2013-01-01

    In an attempt to explore cynomolgus monkeys as an animal model for Alzheimer's disease, the present study focused on the Alzheimer's biomarkers beta amyloid 1-42 (Aβ42 ) in serum, and total tau (t-tau) and phosphorylated tau (p-tau) levels in cerebrospinal fluid.......In an attempt to explore cynomolgus monkeys as an animal model for Alzheimer's disease, the present study focused on the Alzheimer's biomarkers beta amyloid 1-42 (Aβ42 ) in serum, and total tau (t-tau) and phosphorylated tau (p-tau) levels in cerebrospinal fluid....

  18. Amyloid beta1–42 and the phoshorylated tau threonine 231 in brains of aged cynomolgus monkeys (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Darusman, Huda Shalahudin; Gjedde, Albert; Sajuthi, Dondin

    2014-01-01

    Pathological hallmarks indicative of Alzheimer's disease (AD), which are the plaques of amyloid beta1-42 and neurofibrillary tangles, were found in brain of aged cynomolgus monkey. The aim of this study was to investigate if aged monkeys exhibiting spatial memory impairment and levels of biomarke...

  19. Selection of appropriate reference genes for RT-qPCR analysis in a streptozotocin-induced Alzheimer's disease model of cynomolgus monkeys (Macaca fascicularis).

    Science.gov (United States)

    Park, Sang-Je; Kim, Young-Hyun; Lee, Youngjeon; Kim, Kyoung-Min; Kim, Heui-Soo; Lee, Sang-Rae; Kim, Sun-Uk; Kim, Sang-Hyun; Kim, Ji-Su; Jeong, Kang-Jin; Lee, Kyoung-Min; Huh, Jae-Won; Chang, Kyu-Tae

    2013-01-01

    Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) has been widely used to quantify relative gene expression because of the specificity, sensitivity, and accuracy of this technique. In order to obtain reliable gene expression data from RT-qPCR experiments, it is important to utilize optimal reference genes for the normalization of target gene expression under varied experimental conditions. Previously, we developed and validated a novel icv-STZ cynomolgus monkey model for Alzheimer's disease (AD) research. However, in order to enhance the reliability of this disease model, appropriate reference genes must be selected to allow meaningful analysis of the gene expression levels in the icv-STZ cynomolgus monkey brain. In this study, we assessed the expression stability of 9 candidate reference genes in 2 matched-pair brain samples (5 regions) of control cynomolgus monkeys and those who had received intracerebroventricular injection of streptozotocin (icv-STZ). Three well-known analytical programs geNorm, NormFinder, and BestKeeper were used to choose the suitable reference genes from the total sample group, control group, and icv-STZ group. Combination analysis of the 3 different programs clearly indicated that the ideal reference genes are RPS19 and YWHAZ in the total sample group, GAPDH and RPS19 in the control group, and ACTB and GAPDH in the icv-STZ group. Additionally, we validated the normalization accuracy of the most appropriate reference genes (RPS19 and YWHAZ) by comparison with the least stable gene (TBP) using quantification of the APP and MAPT genes in the total sample group. To the best of our knowledge, this research is the first study to identify and validate the appropriate reference genes in cynomolgus monkey brains. These findings provide useful information for future studies involving the expression of target genes in the cynomolgus monkey.

  20. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

    Science.gov (United States)

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

    2016-01-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  1. Large-scale analysis of Macaca fascicularis transcripts and inference of genetic divergence between M. fascicularis and M. mulatta

    Directory of Open Access Journals (Sweden)

    Sugano Sumio

    2008-02-01

    Full Text Available Abstract Background Cynomolgus macaques (Macaca fascicularis are widely used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as rhesus macaques (M. mulatta. We isolated 85,721 clones and determined 9407 full-insert sequences from cynomolgus monkey brain, testis, and liver. These sequences were annotated based on homology to human genes and stored in a database, QFbase http://genebank.nibio.go.jp/qfbase/. Results We found that 1024 transcripts did not represent any public human cDNA sequence and examined their expression using M. fascicularis oligonucleotide microarrays. Significant expression was detected for 544 (51% of the unidentified transcripts. Moreover, we identified 226 genes containing exon alterations in the untranslated regions of the macaque transcripts, despite the highly conserved structure of the coding regions. Considering the polymorphism in the common ancestor of cynomolgus and rhesus macaques and the rate of PCR errors, the divergence time between the two species was estimated to be around 0.9 million years ago. Conclusion Transcript data from Old World monkeys provide a means not only to determine the evolutionary difference between human and non-human primates but also to unveil hidden transcripts in the human genome. Increasing the genomic resources and information of macaque monkeys will greatly contribute to the development of evolutionary biology and biomedical sciences.

  2. Morphologic, stereologic, and morphometric evaluation of the nervous system in young cynomolgus monkeys (Macaca fascicularis) following maternal administration of tanezumab, a monoclonal antibody to nerve growth factor.

    Science.gov (United States)

    Butt, Mark; Evans, Mark; Bowman, Christopher J; Cummings, Thomas; Oneda, Satoru; Shelton, David; Zorbas, Mark

    2014-12-01

    Tanezumab, an antibody to nerve growth factor, was administered to pregnant cynomolgus monkeys at 0, 0.5, 4, and 30 mg/kg weekly, beginning gestation day (GD) 20 through parturition (∼GD165). Maternal tanezumab administration appeared to increase stillbirths and infant mortality, but no consistent pattern of gross and/or microscopic change was detected to explain the mortality. Offspring exposed in utero were evaluated at 12 months of age using light microscopy (all tissues), stereology (basal forebrain cholinergic and dorsal root ganglia neurons), and morphometry (sural nerve). Light microscopy revealed decreased number of neurons in sympathetic ganglia (superior mesenteric, cervicothoracic, and ganglia in the thoracic sympathetic trunk). Stereologic assessment indicated an overall decrease in dorsal root ganglion (thoracic) volume and number of neurons in animals exposed to tanezumab 4 mg/kg (n = 9) and 30 mg/kg (n = 1). At all tanezumab doses, the sural nerve was small due to decreases in myelinated and unmyelinated axons. Existing axons/myelin sheaths appeared normal when viewed with light and transmission electron microscopy. There was no indication of tanezumab-related, active neuron/nerve fiber degeneration/necrosis in any tissue, indicating decreased sensory/sympathetic neurons and axonal changes were due to hypoplasia or atrophy. These changes in the sensory and sympathetic portions of the peripheral nervous system suggest some degree of developmental neurotoxicity, although what effect, if any, the changes had on normal function and survival was not apparent. Overall, these changes were consistent with published data from rodent studies.

  3. Osseointegration of dental implants in Macaca fascicularis

    Science.gov (United States)

    Dewi, R. S.; Odang, R. W.; Odelia, L.

    2017-08-01

    Osseointegration is an important factor in determining the success of a dental implant. It can be assessed from the osseointegration that occurs between the implant and the bone. The implant stability is determined by the osseous support at the implant-bone interface, which is commonly evaluated by histomorphometric analysis. This study aimed to evaluate whether the osseointegration level measured by a Low Resonance Frequency Analyzer (LRFA) gave results as good as those obtained by histomorphometric examination. Six male Macaca fascicularis were used in this study. In each animal, two types of loading were performed: immediate and delayed loading. Clinical examination and LRFA measurement were performed to determine osseointegration at the first and second weeks and at the first, second, third, and fourth months. After four months, histomorphometric examination was performed. The relationship between the histomorphometric examination and LRFA measurement was compared using the Pearson correlation coefficient. There was no significant difference in the osseointegration between immediate loading and delayed loading (p > 0.05) The bone-implant contact percentage in the first group did not differ significantly from that in the second group. Statistical analysis showed that there was a strong correlation between LRFA measurement and histomorphometric examination. Osseointegration could be evaluated through LRFA measurement as well as through histomorphometric examination.

  4. Development of an integrative database with 499 novel microsatellite markers for Macaca fascicularis

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    Higashino Atsunori

    2009-06-01

    Full Text Available Abstract Background Cynomolgus macaques (Macaca fascicularis are a valuable resource for linkage studies of genetic disorders, but their microsatellite markers are not sufficient. In genetic studies, a prerequisite for mapping genes is development of a genome-wide set of microsatellite markers in target organisms. A whole genome sequence and its annotation also facilitate identification of markers for causative mutations. The aim of this study is to establish hundreds of microsatellite markers and to develop an integrative cynomolgus macaque genome database with a variety of datasets including marker and gene information that will be useful for further genetic analyses in this species. Results We investigated the level of polymorphisms in cynomolgus monkeys for 671 microsatellite markers that are covered by our established Bacterial Artificial Chromosome (BAC clones. Four hundred and ninety-nine (74.4% of the markers were found to be polymorphic using standard PCR analysis. The average number of alleles and average expected heterozygosity at these polymorphic loci in ten cynomolgus macaques were 8.20 and 0.75, respectively. Conclusion BAC clones and novel microsatellite markers were assigned to the rhesus genome sequence and linked with our cynomolgus macaque cDNA database (QFbase. Our novel microsatellite marker set and genomic database will be valuable integrative resources in analyzing genetic disorders in cynomolgus macaques.

  5. Comparison of the Effects of Ketamine, Ketamine–Medetomidine, and Ketamine–Midazolam on Physiologic Parameters and Anesthesia-Induced Stress in Rhesus (Macaca mulatta) and Cynomolgus (Macaca fascicularis) Macaques

    OpenAIRE

    Lee, Vanessa K; Flynt, Kendall S; Haag, Lauren M; Taylor, Douglas K.

    2010-01-01

    This study compared the cardiovascular, respiratory, anesthetic, and glucocorticoid effects of ketamine alone with ketamine–medetomidine and ketamine–midazolam in rhesus and cynomolgus macaques. Macaques were given either intramuscular ketamine (10 mg/kg), intramuscular ketamine–medetomidine (3 mg/kg; 0.15 mg/kg), or oral midazolam (1 mg/kg) followed by intramuscular ketamine (8 mg/kg). The addition of medetomidine, but not midazolam, provided muscle relaxation and abolishment of reflexes tha...

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

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Ribeiro Andrade

    2004-10-01

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

  7. Influence of testosterone and a novel SARM on gene expression in whole blood of Macaca fascicularis.

    Science.gov (United States)

    Riedmaier, Irmgard; Tichopad, Ales; Reiter, Martina; Pfaffl, Michael W; Meyer, Heinrich H D

    2009-04-01

    Anabolic hormones, including testosterone, have been suggested as a therapy for aging-related conditions, such as osteoporosis and sarcopenia. These therapies are sometimes associated with severe androgenic side effects. A promising alternative to testosterone replacement therapy are selective androgen receptor modulators (SARMs). SARMs have the potential to mimic the desirable central and peripheral androgenic anabolic effects of testosterone without having its side effects. In this study we evaluated the effects of LGD2941, in comparison to testosterone, on mRNA expression of selected target genes in whole blood in an non-human model. The regulated genes can act as potential blood biomarker candidates in future studies with AR ligands. Cynomolgus monkeys (Macaca fascicularis) were treated either with testosterone or LGD2941 for 90 days in order to compare their effects on mRNA expression in blood. Blood samples were taken before SARM application, on day 16 and on day 90 of treatment. Gene expression of 37 candidate genes was measured using quantitative real-time RT-PCR (qRT-PCR) technology. Our study shows that both testosterone and LGD2941 influence mRNA expression of 6 selected genes out of 37 in whole blood. The apoptosis regulators CD30L, Fas, TNFR1 and TNFR2 and the interleukins IL-12B and IL-15 showed significant changes in gene expression between control and the treatment groups and represent potential biomarkers for androgen receptor ligands in whole blood.

  8. Identification and Characterization of MicroRNAs in Macaca fascicularis by EST Analysis

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    Hao Yang

    2012-01-01

    Full Text Available MicroRNAs (miRNAs are small noncoding RNAs which repress gene expression at the posttranscriptional level. In this study, an expressed sequence tag (EST-based combined method was applied for the detection of miRNAs in Macaca fascicularis which is used as a model animal extensively in medical experiments, particularly those involved with neuroscience and disease. Initially, previously known miRNA sequences from metazoans were used to blast with the EST databases of Macaca fascicularis, and then a range of filtering criteria was conducted to remove some pseudo ones. At last a total of 8 novel conserved miRNAs were identified; their functions were further predicted and analyzed. Together, our study provides insight into miRNAs and their functions in Macaca fascicularis, indicating that the EST analysis is an efficient and affordable alternative approach for identifying novel miRNA candidates.

  9. The Vgamma2/Vdelta2 T-cell repertoire in Macaca fascicularis: functional responses to phosphoantigen stimulation by the Vgamma2/Jgamma1.2 subset.

    Science.gov (United States)

    Cairo, Cristiana; Propp, Nadia; Hebbeler, Andrew M; Colizzi, Vittorio; Pauza, C David

    2005-06-01

    Circulating Vgamma2/Vdelta2 T cells in human and non-human primates respond to small molecular weight non-peptidic phosphoantigens in a major histocompatibility complex (MHC)-unrestricted manner. These responses are encoded by the Vgamma2/Jgamma1.2 chain of the T-cell receptor and are positively selected during early development to create a biased repertoire in adults. We characterized the Vgamma2 chain in cynomolgus macaques (Macaca fascicularis) to develop a non-human primate model for studying the effects of infection and therapy on the circulating Vgamma2/Vdelta2 T-cell subset. The cynomolgus macaque Vgamma2 chain was highly homologous to the Vgamma2 chain from human beings and rhesus macaques (Macaca mulatta), though we noted conserved substitutions in critical residues within the CDR3 for both macaque species. Despite these substitutions, Vgamma2/Vdelta2+ T cells from cynomolgus monkeys exhibited polyclonal responses to two different phosphoantigens. Proliferative responses were observed with both isopentenylpyrophosphate and alendronate, but stronger interferon-gamma secretory responses were observed with isopentenylpyrophosphate. In vitro stimulation and expansion led to selective outgrowth of the Vgamma2/Jgamma1.2 subset, with a marked shift in the Vgamma2 spectratype. As a result of the less biased starting repertoire for Vgamma2, the cynomolgus macaque constitutes a sensitive model for examining the effects of in vitro or in vivo treatments on the Vgamma2/Vdelta2 T-cell population. Our studies establish the value of cynomolgus macaques as a model for Vgamma2/Vdelta2 T-cell responses to non-peptidic antigens, and further evidence the remarkable evolutionary conservation of this unusual, phosphoantigen-responsive T-cell subset that is found only in primate species.

  10. The Vγ2/Vδ2 T-cell repertoire in Macaca fascicularis: functional responses to phosphoantigen stimulation by the Vγ2/Jγ1.2 subset

    Science.gov (United States)

    Cairo, Cristiana; Propp, Nadia; Hebbeler, Andrew M; Colizzi, Vittorio; Pauza, C David

    2005-01-01

    Circulating Vγ2/Vδ2 T cells in human and non-human primates respond to small molecular weight non-peptidic phosphoantigens in a major histocompatibility complex (MHC)-unrestricted manner. These responses are encoded by the Vγ2/Jγ1.2 chain of the T-cell receptor and are positively selected during early development to create a biased repertoire in adults. We characterized the Vγ2 chain in cynomolgus macaques (Macaca fascicularis) to develop a non-human primate model for studying the effects of infection and therapy on the circulating Vγ2/Vδ2 T-cell subset. The cynomolgus macaque Vγ2 chain was highly homologous to the Vγ2 chain from human beings and rhesus macaques (Macaca mulatta), though we noted conserved substitutions in critical residues within the CDR3 for both macaque species. Despite these substitutions, Vγ2/Vδ2+ T cells from cynomolgus monkeys exhibited polyclonal responses to two different phosphoantigens. Proliferative responses were observed with both isopentenylpyrophosphate and alendronate, but stronger interferon-γ secretory responses were observed with isopentenylpyrophosphate. In vitro stimulation and expansion led to selective outgrowth of the Vγ2/Jγ1.2 subset, with a marked shift in the Vγ2 spectratype. As a result of the less biased starting repertoire for Vγ2, the cynomolgus macaque constitutes a sensitive model for examining the effects of in vitro or in vivo treatments on the Vγ2/Vδ2 T-cell population. Our studies establish the value of cynomolgus macaques as a model for Vγ2/Vδ2 T-cell responses to non-peptidic antigens, and further evidence the remarkable evolutionary conservation of this unusual, phosphoantigen-responsive T-cell subset that is found only in primate species. PMID:15885125

  11. STEREOLOGICAL ANALYSIS OF THE COCHLEAR NUCLEI OF MONKEY (MACACA FASCICULARIS AFTER DEAFFERENTATION

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    Ana M Insausti

    2011-05-01

    Full Text Available The cochlear nuclei (CN in the brainstem receive the input signals from the inner ear through the cochlear nerve, and transmit these signals to higher auditory centres. A variety of lesions of the cochlear nerve cause deafness. As reported in the literature, artificial removal of auditive input, or 'deafferentation', induces structural alterations in the CN. The purpose of this study was to estimate a number of relevant stereological parameters of the CN in control and deafferented Macaca fascicularis monkeys.

  12. High resolution karyotype of Thai crab-eating macaque (Macaca fascicularis

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    Fan Xiaobo

    2014-01-01

    Full Text Available Comparative chromosome banding analysis and/or fluorescence in situ hybridization (FISH studies are established approaches to compare human and ape chromosomes. FISH banding is a relatively new and not routinely applied method very well suited to provide to a better understanding of the evolutionary history of primate and human phylogeny. Here multicolor banding (MCB-applying probes derived from Homo sapiens were used to analyze the chromosomes of Thai crab-eating macaque (Macaca fascicularis. The results agree with those of previous studies in other macaques, e.g. Macaca sylvanus or Macaca nemestrina. This result highlights that morphological differences within the Cercopithecoidea must be found rather in subchromosomal changes or even in epigenetics than in gross structural alterations.

  13. High resolution karyotype of thai crab-eating macaque (Macaca fascicularis

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    Fan Xiaobo

    2014-01-01

    Full Text Available Comparative chromosome banding analysis and/or fluorescence in situ hybridization (FISH studies are established approaches to compare human and ape chromosomes. FISH-banding is a relatively new and not routinely applied method suited very well to provide to a better understanding of the evolutionary history of primate and human phylogeny. Here multicolor banding (MCB applying probes derived from Homo sapiens was used to analyze the chromosomes of Thai crab-eating macaque (Macaca fascicularis. The results agree with those of previous studies in other macaques, e.g. Macaca sylvanus or Macaca nemestrina. This result pinpoints, that morphological differences within the Ceropithecoidae must be founded rather in subchromosomal changes or even in epigenetics than in gross structural alterations.

  14. AKTIVITAS HARIAN KERA EKOR PANJANG (Macaca fascicularis DI TAMAN WISATA ALAM SANGEH, KABUPATEN BADUNG, BALI

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    Komang Gede Wahyu Saputra

    2015-02-01

    Full Text Available Penelitian tentang aktivitas harian kera ekor panjang (Macaca fascicularis telah dilakukan di Taman Wisata Alam Sangeh, Kabupaten Badung, Bali dari bulan Oktober – Desember 2012. Penelitian ini bertujuan untuk mengetahui perilaku harian kera ekor panjang (M.  fascicularis di Taman Wisata Alam Sangeh. Penelitian perilaku harian kera dilakukan dengan metode Focal Animal Sampling. Data yang terkumpul dari berbagai jenis perilaku di analisa secara deskriptif kuantitatif. Hasil penelitian menunjukan bahwa frekuensi aktivitas harian kera ekor panjang didominasi oleh perilaku bergerak, kemudian berturut-turut diikuti oleh perilaku istirahat, makan, grooming, mendekap di dada, objek manipulasi, cuddling, agresif. sedangkan perilaku yang paling jarang dilakukan adalah kawin. Berdasarkan jenis kelamin individu dewasa, perilaku istirahat, makan, bergerak, agresif, objek manipulasi dan kawin didominasi oleh jantan sedangkan perilaku mendekap di dada, cuddling, dan grooming di dominasi oleh betina.

  15. Mitochondrial DNA and two Y-chromosome genes of common long-tailed macaques (Macaca fascicularis fascicularis) throughout Thailand and vicinity.

    Science.gov (United States)

    Bunlungsup, Srichan; Imai, Hiroo; Hamada, Yuzuru; Matsudaira, Kazunari; Malaivijitnond, Suchinda

    2017-02-01

    Macaca fascicularis fascicularis is distributed over a wide area of Southeast Asia. Thailand is located at the center of their distribution range and is the bridge connecting the two biogeographic regions of Indochina and Sunda. However, only a few genetic studies have explored the macaques in this region. To shed some light on the evolutionary history of M. f. fascicularis, including hybridization with M. mulatta, M. f. fascicularis and M. mulatta samples of known origins throughout Thailand and the vicinity were analyzed by molecular phylogenetics using mitochondrial DNA (mtDNA), including the hypervariable region 1, and Y-chromosomal DNA, including SRY and TSPY genes. The mtDNA phylogenetic analysis divided M. f. fascicularis into five subclades (Insular Indonesia, Sundaic Thai Gulf, Vietnam, Sundaic Andaman sea coast, and Indochina) and revealed genetic differentiation between the two sides of the Thai peninsula, which had previously been reported as a single group of Malay peninsular macaques. From the estimated divergence time of the Sundaic Andaman sea coast subclade, it is proposed that after M. f. fascicularis dispersed throughout Southeast Asia, some populations on the south-easternmost Indochina (eastern Thailand, southern Cambodia and southern Vietnam at the present time) migrated south-westwards across the land bridge, which was exposed during the glacial period of the late Pleistocene epoch, to the southernmost Thailand/northern peninsular Malaysia. Then, some of them migrated north and south to colonize the Thai Andaman sea coast and northern Sumatra, respectively. The SRY-TSPY phylogenetic analysis suggested that male-mediated gene flow from M. mulatta southward to M. f. fascicularis was restricted south of, but close to, the Isthmus of Kra. There was a strong impact of the geographical factors in Thailand, such as the Isthmus of Kra, Nakhon Si Thammarat, and Phuket ranges and Sundaland, on M. f. fascicularis biogeography and their hybridization

  16. Pharmacokinetics of 2 Formulations of Buprenorphine in Macaques (Macaca mulatta and Macaca fascicularis)

    OpenAIRE

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the ...

  17. Infeksi Cacing Saluran Pencernaan Monyet Ekor Panjang (Macaca fascicularis Yang Diperdagangkan Di Pasar Satria Denpasar

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    Kadek Ari Dwipayanti

    2014-02-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui jenis dan intensitas serta prevalensi infeksi cacing saluran pencernaan pada monyet ekor panjang (Macaca fascicularis yang diperdagangkan di Pasar Satria Denpasar. Empat puluh lima sampel feses M. fascicularis (24 ekor monyet betina dan 21 ekor monyet jantan diambil secara aseptis, diberi label dan selanjutnya diperiksa di laboratorium Parasitologi FKH Universitas Udayana. Sampel diperiksa menggunakan metode konsentrasi sedimentasi untuk mengidentifikasi jenis cacing dan modifikasi McMaster untuk mengetahui intensitas infeksi. Jenis cacing saluran pencernaan yang berhasil diidentifikasi berturut-turut adalah Ancylostoma sp. (91,1%, Trichostrongylus sp./Oesophagostonum sp. (73,3%, Trichuris sp. (22,2%, Ascaris sp. dan Taenia sp. (4,4%. Rataan intensitas infeksi cacing      Ancylostoma sp. 4913 ± 4849 telur per gram tinja, Thrichostrongylus sp./ Oesophagostonum sp. 871 ± 816 telur per gram tinja, Trichuris sp. berkisar      171 ± 111 telur per gram tinja. Ascaris sp. dan Taenia sp. memiliki intensitas terendah yakni <100 telur per gram tinja. Secara umum prevalensi kecacingan adalah 93,3%. Prevalensi kecacingan pada monyet betina (52,2% sedangkan pada monyet jantan (48,8%. Berdasarkan umur, prevalensi kecacingan pada anakan, bayi, dan dewasa berturut-turut (72,1%, (25,6%, dan (2,3%. Pola infeksi umumnya tipe infeksi campuran (82,3% dibandingkan infeksi tunggal (17,7%.

  18. Dietary Variation of Long Tailed Macaques (Macaca fascicularis in Telaga Warna, Bogor, West Java

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    Sarah Nila

    2014-03-01

    Full Text Available The genus Macaca, member of sub-family Cercopithecinae, is the most widely distributed non-human primates in Asian countries. The habitats are strongly influence the dietary variation of the populations. The dietary variation of the macaques reflect ecological plasticity in coping with differences both in availability and abundance of food. The macaques are plastic in taking any kind of food that available in their home range and adjust their behaviour according to its abundance. Here, we present the dietary variation of long-tailed macaques (Macaca fascicularis in the high altitude rain forest of Telaga Warna, West Java, Indonesia. The proportion of their food from natural sources is greater than those from visitors. The natural food consisted of plants, small animals (insects and earthworm, fungi and water from lake. The plant food comprised of 29 species plus a few mosses. The frequency of eating artificial food was influenced by visitors who come for picnic. In this site, the macaques learned that the visiting of tourists is identical with food.

  19. Collection of Macaca fascicularis cDNAs derived from bone marrow, kidney, liver, pancreas, spleen, and thymus

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    Kameoka Yosuke

    2009-09-01

    Full Text Available Abstract Background Consolidating transcriptome data of non-human primates is essential to annotate primate genome sequences, and will facilitate research using non-human primates in the genomic era. Macaca fascicularis is a macaque monkey that is commonly used for biomedical and ecological research. Findings We constructed cDNA libraries of Macaca fascicularis, derived from tissues obtained from bone marrow, liver, pancreas, spleen, and thymus of a young male, and kidney of a young female. In total, 5'-end sequences of 56,856 clones were determined. Including the previously established cDNA libraries from brain and testis, we have isolated 112,587 cDNAs of Macaca fascicularis, which correspond to 56% of the curated human reference genes. Conclusion These sequences were deposited in the public sequence database as well as in-house macaque genome database http://genebank.nibio.go.jp/qfbase/. These data will become valuable resources for identifying functional parts of the genome of macaque monkeys in future studies.

  20. Pharmacokinetics of 2 formulations of buprenorphine in macaques (Macaca mulatta and Macaca fascicularis).

    Science.gov (United States)

    Nunamaker, Elizabeth A; Halliday, Lisa C; Moody, David E; Fang, Wenfang B; Lindeblad, Matthew; Fortman, Jeffrey D

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tested doses. The low and high doses of buprenorphine had elimination half-lives of 2.6 ± 0.7 and 5.3 ± 2.0 h, respectively, but the low-dose data were constrained by the sensitivity of the analytical method. Sustained-release buprenorphine had an elimination half-life of 42.6 ± 26.2 h. The AUC0-Tlast of buprenorphine were 9.1 ± 4.3 and 39.0 ± 25.1 ng × h/mL for the low and high doses, respectively, and sustained-release buprenorphine had an AUC0-Tlast of 177 ± 74 ng × h/mL. Assuming a hypothesized therapeutic buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h. These results further demonstrate that a single 0.2-mg/kg SC injection of sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL for 5 d in macaques. These findings support a new dosing strategy using sustained-release buprenorphine to improve pain management, decrease animal stress, improve animal welfare, and simplify the postoperative management of nonhuman primates in laboratory animal and zoological settings.

  1. Nutritional Composition of Fruits Selected by Long-Tailed Macaques (Macaca fascicularis) in Kuala Selangor, Malaysia.

    Science.gov (United States)

    Kassim, Norazila; Hambali, Kamarul; Amir, Aainaa

    2017-01-01

    Proximate analysis of twelve species of fruits commonly consumed by long-tailed macaques (Macaca fascicularis), i.e., Arenga pinnata, Areca catechu, Terminalia catappa, Elaeis guineensis, Lagerstroemia tomentosa, Mangifera indica, Cascabela thevetia, Muntingia calabura, Musa sp., Artocarpus heterophyllus, Ficus tinctoria ssp. gibbosa and Ficus microcarpa, was conducted with the specific objective to determine the nutritional composition of the foodstuffs of long-tailed macaques. The results showed the following order of nutrients: fibre, protein, fat and ash. Based on the results of the chemical analysis, the highest percentage of fibre content (52.7%), protein (9.9%), fat (77.2%) and ash (8.5%) were found in A. catechu, T. catappa, E. guineensis and C. thevetia, respectively. The nutrient composition of these twelve fruit species was found to differ (ANOVA test: crude protein, F (11,24) = 87.978, p < 0.05; crude fibre, F (11,24) = 28.886, p < 0.05; crude fat, F (11,24) = 2081.396, p < 0.05 and ash, F (11,24) = 41.011, p < 0.05). Fibre was found in the highest amount among the four types of nutrients studied. Here, A. catechu had the highest relative fibre content of all tested fruits, E. guineensis had the highest fat content, T. catappa had the highest protein content, and the total mineral content was highest in C. thevetia.

  2. Genetic diversity and population structure of long-tailed macaque (Macaca fascicularis) populations in Peninsular Malaysia.

    Science.gov (United States)

    Nikzad, Sonia; Tan, Soon Guan; Yong Seok Yien, Christina; Ng, Jillian; Alitheen, Noorjahan Banu; Khan, Razib; Rovie-Ryan, Jeffrine J; Valdiani, Alireza; Khajeaian, Parastoo; Kanthaswamy, Sree

    2014-12-01

    The genetic diversity and structure of long-tailed macaques (Macaca fascicularis) in Peninsular Malaysia, a widely used non-human primate species in biomedical research, have not been thoroughly characterized. Thirteen sites of wild populations of long-tailed macaques representing six states were sampled and analyzed with 18 STR markers. The Sunggala and Penang Island populations showed the highest genetic diversity estimates, while the Jerejak Island population was the most genetically discrete due to isolation from the mainland shelf. Concordant with pairwise F(st) estimates, STRUCTURE analyses of the seven PCA-correlated clusters revealed low to moderate differentiation among the sampling sites. No association between geographic and genetic distances exists, suggesting that the study sites, including island study sites, are genetically if not geographically contiguous. The status of the genetic structure and composition of long-tailed macaque populations require further scrutiny to develop this species as an important animal model in biomedical research. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Nutritional Composition of Fruits Selected by Long-Tailed Macaques (Macaca fascicularis) in Kuala Selangor, Malaysia

    Science.gov (United States)

    Kassim, Norazila; Hambali, Kamarul; Amir, Aainaa

    2017-01-01

    Proximate analysis of twelve species of fruits commonly consumed by long-tailed macaques (Macaca fascicularis), i.e., Arenga pinnata, Areca catechu, Terminalia catappa, Elaeis guineensis, Lagerstroemia tomentosa, Mangifera indica, Cascabela thevetia, Muntingia calabura, Musa sp., Artocarpus heterophyllus, Ficus tinctoria ssp. gibbosa and Ficus microcarpa, was conducted with the specific objective to determine the nutritional composition of the foodstuffs of long-tailed macaques. The results showed the following order of nutrients: fibre, protein, fat and ash. Based on the results of the chemical analysis, the highest percentage of fibre content (52.7%), protein (9.9%), fat (77.2%) and ash (8.5%) were found in A. catechu, T. catappa, E. guineensis and C. thevetia, respectively. The nutrient composition of these twelve fruit species was found to differ (ANOVA test: crude protein, F (11,24) = 87.978, p < 0.05; crude fibre, F (11,24) = 28.886, p < 0.05; crude fat, F (11,24) = 2081.396, p < 0.05 and ash, F (11,24) = 41.011, p < 0.05). Fibre was found in the highest amount among the four types of nutrients studied. Here, A. catechu had the highest relative fibre content of all tested fruits, E. guineensis had the highest fat content, T. catappa had the highest protein content, and the total mineral content was highest in C. thevetia. PMID:28228918

  4. Experimental and postexperimental effects of posteriorly directed extraoral traction in adult Macaca fascicularis.

    Science.gov (United States)

    Brandt, H C; Shapiro, P A; Kokich, V G

    1979-03-01

    The experimental, postexperimental, and postretention effects of continuous high-pull headgear force application to the maxilla were evaluated in four adult, nongrowing Macaca fascicularis monkeys. Force was applied at 450 grams per side to face-bows attached to cast maxillary splints with an implanted occipital plug for anchorage. The active experimental phase lasted from 84 days to 205 days, and its effects were documented histologically, cephalometrically, and with dry skull preparations. Postexperimental, retention, and postretention responses were documented cephalometrically. The findings of the present investigation lead to the following conclusions: 1. The termination active sutural growth is of little significance to the remodeling potential of the sutural articulations and the morphologic adaptability of the facial skeletal complex. 2. The length of time necessary for resorptive remodeling of the sutural bony projections is partially responsible for the slower rate of detectable skeletal movement in adult animals. 3. The sutural ligament in adult animals is initially less responsive to the effects of extraoral force application, possibly because of a diminished level of cellular activity at older ages. 4. Increases in age do not appear to affect the osteogenic potential of the periosteal envelope. 5. Retention aids in establishing a maintainable equilibrium following experimentally induced sutural and skeletal remodeling, but it is of little importance in maintaining the altered position of the denition. 6. The amount of postexperimental skeletal reorientation following force application to the maxilla may be related to the force level and the duration of force.

  5. First Complete Genome Sequence of a Simian Foamy Virus Isolate from a Cynomolgus Macaque

    Science.gov (United States)

    Sakai, Koji; Ami, Yasushi; Suzaki, Yuriko

    2016-01-01

    We report here the first complete proviral genome sequence (DDBJ/ENA/GenBank accession no. LC094267) of a simian foamy virus, SFVmfa/Cy5061, isolated from a cynomolgus macaque (Macaca fascicularis). This proviral genome consists of 12,965 nucleotides and has five open reading frames, gag, pol, env, tas, and bet, as with other foamy viruses. PMID:27908992

  6. The influence of exposure to UVβ of fluorescent light on the bone remodeling of hypoestrogenic Macaca fascicularis

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    I. A. Rachman

    2001-06-01

    Full Text Available The prevention of osteoporosis is a spesific problem that should be dealt with by increasing the women's lift expectation. The decrease of calcitriol and estrogen levels, which have a receptor in the osteoblast, will result in bone mineralization (due to calcitriol and the information of type 1 collagen (due to estrogen. The formation of calcitriol with the main basic materials from vitamin D3 is achieved with the aid of sunray UVβ, The changes in the lifestyle of women, which make them now accustomed to performing indoor activities and prevent them from being exposed to UVβ all day, have resulted in the decrease of vitamin D3 in calcitriol in women. In addition, when entering the menopausal age they will be threatened with early osteoporosis. The exposure to the UVβ of fluorescent light with the wave length identical to sun of 290-320 nm has long been known as a modality for treating skin diseases in the hope that the production of vitamin D3  will be increased. We exposed Macaca fascicularis, whose estrogen levels were set at normal, beginning low, beginning very low levels, to UVβ of fluorescent light. It showed that the Macaca fascicularis that were exposed to UVβ experienced an increase in osteocalcin with unchanged DPD which means that bone remodeling remains unchanged. By contrast, Macaca fascicularis with normal, beginning low, and beginning very low estrogen levels which were not exposed to UVβ were found to experience a decrease in osteocalcin and unchanged DPD levels. This means that a change has occurred in the bone remodeling toward bone resorption. (Med J Indones 2001; 10: 63-8Keywords: UVβ, osteoporosis, estrogen, vitamin D3, calcitriol, osteocalcin, DPD

  7. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    Science.gov (United States)

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

    Science.gov (United States)

    Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

    2015-08-01

    A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

  9. Jaw-muscle architecture and mandibular morphology influence relative maximum jaw gapes in the sexually dimorphic Macaca fascicularis.

    Science.gov (United States)

    Terhune, Claire E; Hylander, William L; Vinyard, Christopher J; Taylor, Andrea B

    2015-05-01

    Maximum jaw gape is a performance variable related to feeding and non-feeding oral behaviors, such as canine gape displays, and is influenced by several factors including jaw-muscle fiber architecture, muscle position on the skull, and jaw morphology. Maximum gape, jaw length, and canine height are strongly correlated across catarrhine primates, but relationships between gape and other aspects of masticatory apparatus morphology are less clear. We examine the effects of jaw-adductor fiber architecture, jaw-muscle leverage, and jaw form on gape in an intraspecific sample of sexually dimorphic crab-eating macaques (Macaca fascicularis). As M. fascicularis males have relatively larger maximum gapes than females, we predict that males will have muscle and jaw morphologies that facilitate large gape, but these morphologies may come at some expense to bite force. Male crab-eating macaques have relatively longer jaw-muscle fibers, masseters with decreased leverage, and temporomandibular joint morphologies that facilitate the production of wide gapes. Because relative canine height is correlated with maximum gape in catarrhines, and males have relatively longer canines than females, these results support the hypothesis that male M. fascicularis have experienced selection to increase maximum gape. The sexes do not differ in relative masseter physiologic cross-sectional area (PCSA), but males compensate for a potential trade-off between muscle excursion versus muscle force with increased temporalis weight and PCSA. This musculoskeletal configuration is likely functionally significant for behaviors involving aggressive canine biting and displays in male M. fascicularis and provides additional evidence supporting the multifactorial nature of the catarrhine masticatory apparatus. Our results have implications for the evolution of craniofacial morphology in catarrhine primates and reinforce the importance of evaluating additional factors other than feeding behavior and diet

  10. Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

    Science.gov (United States)

    2010-09-01

    appearance of very few pox lesions and the appearance of observable clinical disease of short duration just prior to death. Finally, perhaps because of...the small size of the marmosets, blood was not drawn with great frequency and serum chemistries and CBCs were not performed, thus leaving many

  11. The trade balance of grooming and its coordination of reciprocation and tolerance in Indonesian long-tailed macaques (Macaca fascicularis).

    Science.gov (United States)

    Gumert, Michael D; Ho, Moon-Ho R

    2008-07-01

    We collected data on grooming, proximity, and aggression in long-tailed macaques (Macaca fascicularis) in Kalimantan, Indonesia. We used this data to study how grooming influenced a receiver's (B) behavior towards the bout's initiator (A). In our first analysis, post-grooming samples were collected after A groomed B. These were compared to matched-control samples of similar conditions but A had not previously groomed B. This comparison was performed on 26 individuals (16 female, 3 male, 7 immature) and tested whether A's initial act of grooming increased the pair's time in proximity and the amount of time B groomed A. We also tested if A's grooming decreased B's aggression towards A per time in proximity. Rates of B-->A aggression per time in proximity with A for 39 individuals (18 female, 5 male, 16 immature) were compared between post-grooming and focal sample data. Finally, we studied 248 grooming bouts to test if the first two grooming episodes were time matched. We assessed the influence of age, sex, rank and inferred kinship on time matching, and controlled for individual variation and tendency to groom using a general linear mixed model. Our results showed that A-->B grooming acted to increase B-->A grooming and the pair's proximity, while lowering B-->A aggression. Despite these effects, episodes in grooming bouts were generally not matched, except weakly among similar partners (i.e., female pairs and immature pairs). Grooming imbalance was greatest across age-sex class (i.e., male-female and adult-immature pairs). In similar pairs, grooming duration was skewed in favor of high-ranking individuals. We conclude grooming established tolerance and increased the likelihood that grooming reciprocation would occur, but grooming durations were not typically matched within bouts. Lack of time matching may be the result of grooming that is performed to coordinate interchanges of other social services.

  12. The acquisition of Streptococcus mutans by infant monkeys (Macaca fascicularis) and its relationship to the initiation of dental caries.

    Science.gov (United States)

    Beighton, D; Hayday, H; Walker, J

    1982-08-01

    The acquisition and transmission of Streptococcus mutans by 16 consecutively born infant monkeys (Macaca fascicularis) was studied. The 16 infant monkeys were weaned in four groups and caged together to form a commune. Transmission from mother to infant occurred infrequently. Streptococcus mutans was isolated from nine of the mothers but only from the dental plaque of two infant monkeys at weaning at which time the predominant streptococci were S. sanguis and S. mitior. One further animal was colonized by S. mutants during the formation of the commune, but only after it was caged with an infant harbouring the same organism. For 46 d after the completion of the commune, the monkeys were fed a starch-based diet during which time S. mutans of serotypes c, e or h were isolated from the faeces of all 16 animals and from the dental plaque taken from the developmental groove of the first deciduous molar of 11 animals. Faecal transmission appeared to be an important factor in the spread of S. mutans between monkeys in the commune. The monkeys were then fed a caries-promoting high sucrose diet resulting in a rapid increase in the proportion of S. mutans in the plaque and in the faeces. Streptococcus mutans serotype e was more frequently isolated from both plaque and faeces and its predominance may in part be due to the production of a bacteriocin active in vitro against S. mutans serotype h and other species of oral streptococci isolated from monkey dental plaque. The proportion of S. mutans in the developmental groove 8 d after the introduction of the high sucrose diet was significantly related to both the caries status of the groove and the total caries score 6 months later. The results suggest that, in this model of human dental caries, S. mutans is the major bacterial factor in the initiation of tooth decay.

  13. DINAMIKA PROFIL HEMATOLOGI DAN RASIO NETROFIL:LIMFOSIT MONYET EKOR PANJANG (MACACA FASCICULARIS PADA PENGATURAN MIKROKLIMAT RUANGAN

    Directory of Open Access Journals (Sweden)

    Ridzki M.F. Binol

    2010-08-01

    Full Text Available The aim of this study was to obtain the profile of physiological hematology (erythrocyte, PCV, Hb, MCV, MCH, MCHC, and leukocyte and the profile of ratio between neutrophil and lymphocyte of long-tailed macaque (Macaca fascicularis in different microclimate conditions due to the room’s temperature and humidity setting. The symptom of stress was also observed in this study. The research used 10 male macaques aged of 4 until 5 years old which placed in room temperature and humidity of 29,00±1,95°C and 79,52±1,57% respectively 7 days for adaptation period. Further more, the room temperature and humidity were set into 25,79±1,16°C and 80,19±9,05% during 14 days for treatment period. For the last treatment, macaques were reconditioned in room temperature and humidity of 29,00±1,95°C and 79,52±1,57% during 14 days for post-treatment period. Blood samplings were collected through femoralis vein on last day of adaptation period, continued with treatment and post-treatment periods as the day 1, 4, 7, 14, and 28. The results showed that there were not significant difference by room temperature and humidity setting to hematology and neutrophil:lymphocyte ratio. It could be proven by all parameters score obtained were still in normal ranges compared to literatures. There was also no stress symptom based on neutrophil:lymphocyte ratio measurement. Condition with room temperature and humidity of 25,79±1,16°C dan 80,19±9,05% regarded as the most suitable condition for long-tailed macaque’s life

  14. Urban primate ranging patterns: GPS-collar deployments for Macaca fascicularis and M. sylvanus.

    Science.gov (United States)

    Klegarth, Amy R; Hollocher, Hope; Jones-Engel, Lisa; Shaw, Eric; Lee, Benjamin P Y-H; Feeney, Tessa; Holmes, Damian; Laguea, Dale; Fuentes, Agustín

    2017-05-01

    The global increase in urbanization is leading to heavier interface between humans and wildlife. Within these anthropogenic landscapes, little is known about ranging patterns, particularly with regard to urban primates. Here we present the results of the first long-term deployment of multiple GPS collars on two species of macaques to investigate the impacts of urbanization on urban primate ranging patterns in Singapore and Gibraltar. Collars data acquisition were excellent with respect to the amount, quality, and accuracy of data collected; however, remote connectivity and drop-off functionality was poor across all deployments. Analyses highlighted high variability in ranging patterns between individuals within each species that aligned with access to human food resources and patterns of tourism. Individuals from troops with less access to human food had much larger home, core, and day ranges relative to those with regular provisioning or raiding opportunities. Almost no temporal range overlap was observed between any focal individuals at either site and spatial overlap was low for all but two troops at each site. We found no relationship between anthropogenic schedules and changes in ranging patterns. Significant seasonal variation existed for daily path length and day range size for both the Singapore long-tailed and the Gibraltar Barbary macaques, with long-tailed macaques increasing their range during the equatorial monsoon season and Barbary macaques increasing their range during drier, summer months. This study highlights how the behavioral plasticity found within the genus Macaca is reflected in ranging pattern variability within urban environments. © 2017 Wiley Periodicals, Inc.

  15. Functional MRI of brain in macaca fascicularis under alcohol scent stimulation%乙醇气味刺激食蟹猴的脑fMRI

    Institute of Scientific and Technical Information of China (English)

    徐惠; 朱建忠; 孙向东; 赵梦; 李传福

    2011-01-01

    Objective To explore the fMRl changes of brain in macaca fascicularis with alcohol scent stimulation. Methods Six healthy macaca fascicularis were selected and anesthetized. The block design was "rest-stimulation-rest". fMRI under alcohol scent stimulation and resting state were performed, respectively. The animals inhaled air mixed with 95% alcohol in the stimulation period, while inhaled pure air in rest period. BOLD-fMRI sequences and 128 phases scanning were performed, 16 slices axial images of the entire brain and total 2048 images were obtained. Data were analyzed using SPM2. The outcomes were superposed on the template of macaca fascicularis at last. Random effect mode group analysis was applied in estimating and calculating with f-test Results When alcohol scent stimulation was given, increased or decreased BOLD signals were observed in frontal lobe, temporal lobe, paracentral lobules, cingulate gyri, and lenticular nucleus, and anterior central gyrus, respectively. Conclusion Uncus gyri hippocampi and orbitofrontal are the most advanced center of olfaction. The central reaction induced by scent stimulation had an affinity with paracentral lobule, cingulate gyrus and lenticular nucleus.%目的 应用3.0T fMRI探讨食蟹猴经乙醇气味刺激引起的脑功能活动.方法 选取健康食蟹猴6只,麻醉后行乙醇气味刺激下的fMRI.采取“静息-刺激-静息”组块设计.刺激组块予乙醇气味刺激,静息组块无气味刺激.BOLDfMRI扫描128 phase,整个猴脑扫描16层.采用SPM2软件随机效应模式t检验进行组分析.将统计结果覆盖于食蟹猴模板图像上.结果 乙醇气味刺激下,在额叶、颞叶、中央旁小叶、扣带回、豆状核、中央前回分别可以检测到正激活和负激活.结论 海马回钩和眶额回为嗅觉最高级中枢.fMRI可以显示额叶、颞叶的激活.气味刺激引起的中枢反应与中央旁小叶、扣带回、豆状核有密切关系.

  16. Generation of Macaca fascicularis iPS cell line ATCi-MF1 from adult skin fibroblasts using non-integrative Sendai viruses

    Directory of Open Access Journals (Sweden)

    Giulia Coppiello

    2017-05-01

    Full Text Available We generated ATCi-MF1 induced pluripotent stem (iPS cell line from Macaca fascicularis adult skin fibroblasts using non-integrative Sendai viruses carrying OCT3/4, KLF4, SOX2 and c-MYC. Once established, ATCi-MF1 cells present a normal karyotype, are Sendai virus-free and express pluripotency associated markers. Microsatellite markers analysis confirmed the origin of the iPS cells from the parental fibroblasts. Pluripotency was tested with the in vivo teratoma formation assay. ATCi-MF1 cell line may be a useful primate iPS cell model to test different experimental conditions where the use of human cells can imply ethical issues, as microinjection of pluripotent stem cells in pre-implantational embryos.

  17. 小鼠抗食蟹猴IgG单克隆抗体的制备%Preparation Monoclonal Antibodies Of Mice Against Macaca fascicularis IgG

    Institute of Scientific and Technical Information of China (English)

    张段玲; 张彦龙; 白素英

    2012-01-01

    目的 制备抗食蟹猴、恒河猴等非人灵长类实验动物免疫球蛋白二级抗体,开展对其传染病血清学快速诊断方法的建立.方法 采用饱和硫酸铵盐析、Agarose-Protein G亲和层析技术,从食蟹猴血清中提纯IgG.经SDS-PAGE电泳鉴定,采用常规法免疫C57BL/6小鼠,三次免疫后取脾细胞与Sp2/0-Agl4骨髓瘤细胞通过PEG4000融合制备杂交瘤细胞,利用间接ELISA、Western blot等方法进行筛选、鉴定.结果 得到5株阳性杂交瘤,分别命名为2B6、2B7、2D9、3B2、5E4,并且5株杂交瘤分泌的抗体均与恒河猴的IgG或血清发生交叉反应,而与其他物种如东北虎、犬等动物的IgG或血清无交叉反应.结论 5株杂交瘤产生的单克隆抗体(McAb)具有较好免疫活性,且能长期、稳定地分泌抗体.此项研究工作为后续研究食蟹猴、恒河猴传染病血清学诊断方法奠定基础.%Objective In order to prepare imraunoglobulin G (IgG) secondary antibody of non-human primates such as Macaca fascicularis and Macaca mulatta and establish a quick serological method to diagnose their diseases. Methods Macaco fascicularis IgG was isolated and purified from Macaco fascicularis serum by precipitated use saturated ammonium sulfate and affinity chromatography technology with Agarose-Protein G. After identified by SDS-PAGE electrophoresis murine monoclonal antibody ( McAb) were produced by conventional immune method and hybridoma technology. Monoclonal antibody was produced when C57BL/6 mice was immunized three times and its spleen cells were fused with SP2/0-Agl4 myeloma cells. Indirect ELISA and Western blot methods were used for identification. Result 5 strains of myeloma cells acquired which were named 2B6, 2B7, 3B2, 5E4, 2D9. The antibodies they secret can all react well with both IgG and their serum of Macaco fascicularis and Macaca mulatto. There are no cross reaction with other species such as east-northern tigers and dogs. Conclusion The 5

  18. Efficacy of selective PDE4D negative allosteric modulators in the object retrieval task in female cynomolgus monkeys (Macaca fascicularis.

    Directory of Open Access Journals (Sweden)

    Jane S Sutcliffe

    Full Text Available Cyclic adenosine monophosphate (cAMP signalling plays an important role in synaptic plasticity and information processing in the hippocampal and basal ganglia systems. The augmentation of cAMP signalling through the selective inhibition of phosphodiesterases represents a viable strategy to treat disorders associated with dysfunction of these circuits. The phosphodiesterase (PDE type 4 inhibitor rolipram has shown significant pro-cognitive effects in neurological disease models, both in rodents and primates. However, competitive non-isoform selective PDE4 inhibitors have a low therapeutic index which has stalled their clinical development. Here, we demonstrate the pro-cognitive effects of selective negative allosteric modulators (NAMs of PDE4D, D159687 and D159797 in female Cynomolgous macaques, in the object retrieval detour task. The efficacy displayed by these NAMs in a primate cognitive task which engages the corticostriatal circuitry, together with their suitable pharmacokinetic properties and safety profiles, suggests that clinical development of these allosteric modulators should be considered for the treatment of a variety of brain disorders associated with cognitive decline.

  19. Use of Operant Performance to Guide and Evaluate Medical Treatment in an Adult Male Cynomolgus Macaque (Macaca fascicularis)

    Science.gov (United States)

    2011-11-01

    treatment. The affected monkey received ketoprofen , buprenorphine, or their combination but continued to perform poorly during daily operant behavioral...evening administration of buprenorphine (0.01 mg/kg IM) was added to the treatment regimen of ketoprofen (2.0 mg/kg IM) ad- ministration in the...well below the reinforced band. Treatment with ketoprofen or the ketoprofen -buprenorphine combination failed to increase mean response duration

  20. A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis).

    Science.gov (United States)

    Zippo, Antonio G; Romanelli, Pantaleo; Torres Martinez, Napoleon R; Caramenti, Gian C; Benabid, Alim L; Biella, Gabriele E M

    2015-01-01

    Artificial brain-machine interfaces (BMIs) represent a prospective step forward supporting or replacing faulty brain functions. So far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. In this work, a novel 16 channel chronically implantable epicortical grid has been proposed. It provides wireless transmission of cortical recordings and stimulations, with induction current recharge. The grid has been chronically implanted in a non-human primate (Macaca fascicularis) and placed over the somato-motor cortex such that 13 electrodes recorded or stimulated the primary motor cortex and three the primary somatosensory cortex, in the deeply anaesthetized animal. Cortical sensory and motor recordings and stimulations have been performed within 3 months from the implant. In detail, by delivering motor cortex epicortical single spot stimulations (1-8 V, 1-10 Hz, 500 ms, biphasic waves), we analyzed the motor topographic precision, evidenced by tunable finger or arm movements of the anesthetized animal. The responses to light mechanical peripheral sensory stimuli (blocks of 100 stimuli, each single stimulus being detection. In conclusion, we propose a chronically implantable epicortical grid which can accommodate most of current technological restrictions, representing an acceptable candidate for BMI experimental and clinical uses.

  1. Malaria in cynomolgus monkeys used in toxicity studies in Japan.

    Science.gov (United States)

    Ohta, Etsuko; Nagayama, Yuko; Koyama, Naoki; Kakiuchi, Dai; Hosokawa, Satoru

    2016-01-01

    Plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. Here we report both our experience with malaria recrudescence in cynomolgus monkeys (Macaca fascicularis) in a toxicity study and the results of a survey on Plasmodium infection in cynomolgus monkeys imported to Japan for laboratory use. A cynomolgus monkey from the toxicity study presented with severe anemia and Plasmodium protozoa in erythrocytes on a thin blood smear and was subsequently diagnosed with symptomatic malaria. In this animal, congestion and accumulation of hemozoin (malaria pigment) in macrophages were noted in the enlarged and darkly discolored spleen. As a follow-up for the experience, spleen sections from 800 cynomolgus monkeys in toxicity studies conducted between 2003 and 2013 were retrospectively examined for hemozoin deposition as a marker of Plasmodium infection. The origin of the animals included Cambodia, China, Indonesia, and Vietnam. Hemozoin deposition was confirmed in 44% of all examined monkeys. Monkeys from Indonesia showed the highest incidence of hemozoin deposition (approx. 80%). A high prevalence of Plasmodium infection in laboratory monkeys was also confirmed with polymerase chain reaction (PCR) by using Plasmodium genus-specific primers. Although Japan is not a country with endemic malaria, it is important to be aware of the prevalence and potential impact of background infection with Plasmodium spp. and recrudescence of symptomatic malaria in imported laboratory monkeys on pharmaceutical toxicity studies.

  2. Toward reduction in animal sacrifice for drugs: molecular modeling of Macaca fascicularis P450 2C20 for virtual screening of Homo sapiens P450 2C8 substrates.

    Science.gov (United States)

    Rua, Francesco; Di Nardo, Giovanna; Sadeghi, Sheila J; Gilardi, Gianfranco

    2012-01-01

    Macaca fascicularis P450 2C20 shares 92% identity with human cytochrome P450 2C8, which is involved in the metabolism of more than 8% of all prescribed drugs. To date, only paclitaxel and amodiaquine, two substrate markers of the human P450 2C8, have been experimentally confirmed as M. fascicularis P450 2C20 drugs. To bridge the lack of information on the ligands recognized by M. fascicularis P450 2C20, in this study, a three-dimensional homology model of this enzyme was generated on the basis of the available crystal structure of the human homologue P450 2C8 using YASARA. The results indicated that 90.0%, 9.0%, 0.5%, and 0.5% of the residues of the P450 2C20 model were located in the most favorable, allowed, generously allowed, and disallowed regions, respectively. The root-mean-square deviation of the C-alpha superposition of the M. fascicularis P450 2C20 model with the Homo sapiens P450 2C8 was 0.074 Å, indicating a very high similarity of the two structures. Subsequently, the 2C20 model was used for in silico screening of 58 known P450 2C8 substrates and 62 inhibitors. These were also docked in the active site of the crystal structure of the human P450 2C8. The affinity of each compound for the active site of both cytochromes proved to be very similar, meaning that the few key residues that are mutated in the active site of the M. fascicularis P450 do not prevent the P450 2C20 from recognizing the same substrates as the human P450 2C8.

  3. A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis

    Directory of Open Access Journals (Sweden)

    Antonio Giuliano Zippo

    2015-05-01

    Full Text Available Artificial brain-machine interfaces (BMIs represent a prospective step forward supporting or replacing faulty brain functions. So far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. In this work, a novel 16 channel chronically implantable epicortical grid has been proposed. It provides wireless transmission of cortical recordings and stimulations, with induction current recharge. The grid has been chronically implanted in a non-human primate (Macaca fascicularis and placed over the somato-motor cortex such that 13 electrodes recorded or stimulated the primary motor cortex and 3 the primary somatosensory cortex, in the deeply anaesthetized animal. Cortical sensory and motor recordings and stimulations have been performed within 3 months from the implant. In detail, by delivering motor cortex epicortical single spot stimulations (1 to 8V, 1 to 10 Hz, 500ms, biphasic waves, we analyzed the motor topographic precision, evidenced by tunable finger or arm movements of the anesthetized animal. The responses to light mechanical peripheral sensory stimuli (blocks of 100 stimuli, each single stimulus being < 1ms and interblock intervals of 1.5 to 4 s have been analyzed. We found 150 to 250ms delayed cortical responses from fast finger touches, often spread to nearby motor stations. We also evaluated the grid electrical stimulus interference with somatotopic natural tactile sensory processing showing no suppressing interference with sensory stimulus detection. In conclusion, we propose a chronically implantable epicortical grid which can accommodate most of current technological restrictions, representing an acceptable candidate for BMI experimental and clinical uses.

  4. A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis)

    Science.gov (United States)

    Zippo, Antonio G.; Romanelli, Pantaleo; Torres Martinez, Napoleon R.; Caramenti, Gian C.; Benabid, Alim L.; Biella, Gabriele E. M.

    2015-01-01

    Artificial brain-machine interfaces (BMIs) represent a prospective step forward supporting or replacing faulty brain functions. So far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. In this work, a novel 16 channel chronically implantable epicortical grid has been proposed. It provides wireless transmission of cortical recordings and stimulations, with induction current recharge. The grid has been chronically implanted in a non-human primate (Macaca fascicularis) and placed over the somato-motor cortex such that 13 electrodes recorded or stimulated the primary motor cortex and three the primary somatosensory cortex, in the deeply anaesthetized animal. Cortical sensory and motor recordings and stimulations have been performed within 3 months from the implant. In detail, by delivering motor cortex epicortical single spot stimulations (1–8 V, 1–10 Hz, 500 ms, biphasic waves), we analyzed the motor topographic precision, evidenced by tunable finger or arm movements of the anesthetized animal. The responses to light mechanical peripheral sensory stimuli (blocks of 100 stimuli, each single stimulus being <1 ms and interblock intervals of 1.5–4 s) have been analyzed. We found 150–250 ms delayed cortical responses from fast finger touches, often spread to nearby motor stations. We also evaluated the grid electrical stimulus interference with somatotopic natural tactile sensory processing showing no suppressing interference with sensory stimulus detection. In conclusion, we propose a chronically implantable epicortical grid which can accommodate most of current technological restrictions, representing an acceptable candidate for BMI experimental and clinical uses. PMID:26029061

  5. Observations on healing following endodontic surgery in nonhuman primates (Macaca fascicularis): effects of rhBMP-2.

    Science.gov (United States)

    Bergenholtz, Gunnar; Wikesjö, Ulf M E; Sorensen, Rachel G; Xiropaidis, Andreas V; Wozney, John M

    2006-01-01

    The potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) to enhance bone healing following endodontic surgery was tested. The pattern and timing of de novo bone formation and cementum regeneration, and the potential for root resorption and ankylosis to accompany bone formation were evaluated. Pulpal infections were induced in maxillary and mandibular incisor teeth in young adult Cynomolgus monkeys. The teeth received conventional endodontic treatment immediately followed by surgical root resection. In a randomized split-mouth design, contralateral apical bone defects received rhBMP-2 in absorbable collagen sponge (ACS) carrier or served as sham-surgery controls to provide histological and radiographic evaluations following 1 (mandibular incisors) and 4.5 (maxillary incisors) month(s) postsurgery. At 1 month postsurgery trabecular bone filled the apical bone defects. The newly formed bone appeared considerably more mature and had assumed characteristics of the contiguous resident bone at 4.5 months postsurgery. The resected root tips were almost completely covered by new cementum with a maturing functionally oriented periodontal ligament. Localized inflammatory infiltrates were associated with the filled root canals and extruded root-filling material. Root resorption and ankylosis were not observed. There were no apparent differences in healing patterns between sites implanted with rhBMP-2/ACS and those serving as sham-surgery controls. Under conditions where the influence of infectious elements and irritation caused by root filling material are minimized, bone formation and cementum regeneration appears rapid following endodontic surgery. rhBMP-2/ACS did not offer an obvious benefit above and beyond that of the native osteogenic potential in this animal model.

  6. Condylomatous genital lesions in cynomolgus macaques from Mauritius.

    Science.gov (United States)

    Harari, Ariana; Wood, Charles E; Van Doorslaer, Koenraad; Chen, Zigui; Domaingue, Marie Claire; Elmore, David; Koenig, Patricia; Wagner, Janice D; Jennings, Ryan N; Burk, Robert D

    2013-08-01

    Genital condyloma-like lesions were observed on male and female cynomolgus macaque monkeys (Macaca fascicularis) originating from the island of Mauritius. Cytobrush and/or biopsy samples were obtained from lesions of 57 affected macaques. Primary histologic features included eosinophilic, neutrophilic, and lymphoplasmacytic penile and vulvar inflammation, epidermal hyperplasia with acanthosis, and increased collagenous stroma. Polymerase chain reaction-based assays to amplify viral DNA revealed the presence of macaque lymphocryptovirus (LCV) DNA but not papillomavirus or poxvirus DNA. Subsequent DNA analyses of 3 genomic regions of LCV identified isolates associated with lesions in 19/25 (76%) biopsies and 19/57 (33%) cytology samples. Variable immunolabeling for proteins related to the human LCV Epstein Barr Virus was observed within intralesional plasma cells, stromal cells, and epithelial cells. Further work is needed to characterize the epidemiologic features of these lesions and their association with LCV infection in Mauritian-origin macaques.

  7. 食蟹猴动物实验在PET/CT扫描检查中的注意事项%Guidelines for PET/CT scanography in animal experiment of Macaca fascicularis

    Institute of Scientific and Technical Information of China (English)

    杨洪文; 秦朝军

    2012-01-01

    Objective To search for the best scanning parameters of PET/CT scanning examination in animal experiment of Macaca fascicularis, and to obtain the best images. Methods One male and one female monkeys respectively received the CT multiparameter scanning and PET multi - time period dynamic tomoscan. Results When the scanning conditions were 420 mAs and 120 kV,the best resolution ratio and the lightest constructed defect could be obtained. In the images of PET multi - time period dynamic tomoscan, the best image effects could be obtained from the images within 40-60 min. Conclusion Before the animal experiment of Macaca fascicularis on the PET/CT machine, the monkeys should receive the pre - scanning. And the best scanning parameters should be selected in order to obtain satisfactory results in the experiment.%目的 寻找食蟹猴动物实验在PET/CT扫描检查中最佳的扫描参数,获得最佳图像.方法 两只食蟹猴为一雄一雌,对两只食蟹猴分别采用CT多参数扫描和PET的多时段动态断层扫描.结果 扫描条件采用420 mAs、120 kV时,可以获得最佳的图像分辨率和最轻的伪影.PET扫描多时段动态断层扫描的图像中,40~60 min的图像可以获得最佳图像效果.结论 食蟹猴在PET/CT机上行动物实验前,应进行预扫描,选择最佳的扫描参数,才能获得满意的实验结果.

  8. 靶向食蟹猴NTCP基因的CRISPR/Cas9系统gRNA筛选%gRNA Screening of CRISPR/Cas9 System Targeting Macaca fascicularis NTCP Gene

    Institute of Scientific and Technical Information of China (English)

    徐桂利; 高新; 刘铮铸; 巩元芳; 宋海峰

    2016-01-01

    This study was aimed to screen gRNA of efficient knockout activity targeting Macaca fascicularis NTCP gene by the CRISPR/Cas9 enzyme digestion method and PCR amplification methods in vitro .Comparing NTCP gene sequences between Macaca fascicularis and human,the sequences of NTCP gene coding amino acid 84 to 87 and 157 to 1 65 were chosen as gene knockout targets.3 to 4 candidate gRNA sequences were designed in two target sequence regions through gRNA software.By screening cleavage activity targeting NTCP gene in vitro ,gRNA1.2 and gRNA2.1 were selected and inserted into pLV hUbC-Cas9-T2A-GFP plasmid,respectively.The genome DNA was extracted from primary hepatocytes after gRNA1.2 and gRNA2.1 being trans-ferred,respectively.Then NTCP sequences were amplified by PCR and sequenced by being cloned into T vector.The results indicated that compared to gRNA1.2,gRNA2.1 had much higher activ-ity to make a frame-shift mutation in NTCP gene.This study laid a theoretical foundation for fur-ther editing NTCP gene and its biological function in Macaca fascicularis .%本研究旨在通过 CRISPR/Cas9体外酶切法及细胞水平上的 PCR 扩增测序筛选出靶向食蟹猴 NTCP 基因具有高敲除活性的 gRNA。首先通过比对食蟹猴与人类 NTCP 氨基酸序列,选择差异位点,即第84—87位和第157—165位氨基酸作为基因靶点序列区;利用 gRNA 软件设计针对上述基因靶点序列的 gRNA,每个靶点设计3~4条候选 gRNA 序列;然后利用 gRNA 体外检测试剂盒,筛选出靶向 NTCP 基因的体外敲除活性较高的两条gRNA 序列:gRNA1.2和 gRNA2.1。将 gRNA1.2和 gRNA2.1分别插入 pLV hUbC-Cas9-T2A-GFP 载体中,转染食蟹猴原代肝细胞。提取转染后细胞基因组 DNA,通过 PCR 扩增 NTCP 基因并将其克隆到 T 载体中进行测序分析。结果表明,gRNA1.2和 gRNA2.1均可使 NTCP 基因产生移码突变,但 gRNA2.1比 gRNA1.2具有更高的敲除活性。本研究为下一步编辑食蟹猴 NTCP

  9. The role of Branhamella catarrhalis in the "bloody-nose syndrome" of cynomolgus macaques.

    Science.gov (United States)

    VandeWoude, S J; Luzarraga, M B

    1991-10-01

    During a 15-month period, 25 cynomolgus macaques (Macaca fascicularis) at the Johns Hopkins University were observed to have nasal discharge. Fifteen (60%) of these animals had positive nasal cultures for Branhamella catarrhalis. Clinical signs associated with infection by this bacterium were sneezing, epistaxis, and mucohemorrhagic nasal discharge. Treatment with antibiotics resulted in prompt resolution of clinical signs. Post-therapeutic nasal cultures were negative for B. catarrhalis. Two groups of clinically normal, culture-negative, cynomolgus macaques were inoculated with natural isolates of B. catarrhalis which had been passaged in culture for various amounts of time. Five of the eight animals inoculated became culture-positive and had mild nasal discharge. Presence of blood on nasal swabs was indicative of infection with B. catarrhalis. Three of the inoculated animals had post-swabbing epistaxis. This report documents the role of B. catarrhalis as an upper respiratory pathogen in the cynomolgus monkey which causes mild self-limiting disease reminiscent of the so-called "Bloody-Nose Syndrome." In addition to the obvious clinical significance of this finding to primate clinicians, development of an animal model for human disease caused by this organism may be possible.

  10. Characterization and phylogenetic epitope mapping of CD38 ADPR cyclase in the cynomolgus macaque

    Directory of Open Access Journals (Sweden)

    Titti Fausto

    2004-09-01

    Full Text Available Abstract Background The CD38 transmembrane glycoprotein is an ADP-ribosyl cyclase that moonlights as a receptor in cells of the immune system. Both functions are independently implicated in numerous areas related to human health. This study originated from an inherent interest in studying CD38 in the cynomolgus monkey (Macaca fascicularis, a species closely related to humans that also represents a cogent animal model for the biomedical analysis of CD38. Results A cDNA was isolated from cynomolgus macaque peripheral blood leukocytes and is predicted to encode a type II membrane protein of 301 amino acids with 92% identity to human CD38. Both RT-PCR-mediated cDNA cloning and genomic DNA PCR surveying were possible with heterologous human CD38 primers, demonstrating the striking conservation of CD38 in these primates. Transfection of the cDNA coincided with: (i surface expression of cynomolgus macaque CD38 by immunofluorescence; (ii detection of ~42 and 84 kDa proteins by Western blot and (iii the appearance of ecto-enzymatic activity. Monoclonal antibodies were raised against the cynomolgus CD38 ectodomain and were either species-specific or cross-reactive with human CD38, in which case they were directed against a common disulfide-requiring conformational epitope that was mapped to the C-terminal disulfide loop. Conclusion This multi-faceted characterization of CD38 from cynomolgus macaque demonstrates its high genetic and biochemical similarities with human CD38 while the immunological comparison adds new insights into the dominant epitopes of the primate CD38 ectodomain. These results open new prospects for the biomedical and pharmacological investigations of this receptor-enzyme.

  11. The placenta in toxicology. Part I : Animal models in toxicology: placental morphology and tolerance molecules in the cynomolgus monkey (Macaca fascicularis)

    NARCIS (Netherlands)

    Buse, Eberhard; Häeger, Jan-Dirk; Svensson-Arvelund, Judit; Markert, Udo R; Faas, Marijke M; Ernerudh, Jan; Dixon, Darlene; Cline, J Mark; Pfarrer, Christiane

    2014-01-01

    The immune system represents a key defense mechanism against potential pathogens and adverse non-self materials. During pregnancy, the placenta is the point of contact between the maternal organism and non-self proteins of the fetal allograft and hence undoubtedly fulfils immune functions. In the pl

  12. The placenta in toxicology. Part I : Animal models in toxicology: placental morphology and tolerance molecules in the cynomolgus monkey (Macaca fascicularis)

    NARCIS (Netherlands)

    Buse, Eberhard; Häeger, Jan-Dirk; Svensson-Arvelund, Judit; Markert, Udo R; Faas, Marijke M; Ernerudh, Jan; Dixon, Darlene; Cline, J Mark; Pfarrer, Christiane

    The immune system represents a key defense mechanism against potential pathogens and adverse non-self materials. During pregnancy, the placenta is the point of contact between the maternal organism and non-self proteins of the fetal allograft and hence undoubtedly fulfils immune functions. In the

  13. Population and landscape genetics of an introduced species (M. fascicularis) on the island of Mauritius.

    Science.gov (United States)

    Satkoski Trask, Jessica; George, Debra; Houghton, Paul; Kanthaswamy, Sree; Smith, David Glenn

    2013-01-01

    The cynomolgus macaque, Macaca fascicularis, was introduced onto the island of Mauritius in the early 17(th) century. The species experienced explosive population growth, and currently exists at high population densities. Anecdotes collected from nonhuman primate trappers on the island of Mauritius allege that animals from the northern portion of the island are larger in body size than and superior in condition to their conspecifics in the south. Although previous genetic studies have reported Mauritian cynomolgus macaques to be panmictic, the individuals included in these studies were either from the southern/central or an unknown portion of the island. In this study, we sampled individuals broadly throughout the entire island of Mauritius and used spatial principle component analysis to measure the fine-scale correlation between geographic and genetic distance in this population. A stronger correlation between geographic and genetic distance was found among animals in the north than in those in the southern and central portions of the island. We found no difference in body weight between the two groups, despite anecdotal evidence to the contrary. We hypothesize that the increased genetic structure among populations in the north is related to a reduction in dispersal distance brought about by human habitation and tourist infrastructure, but too recent to have produced true genetic differentiation.

  14. Fructosamine reference ranges in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Williams-Fritze, Misty J; Smith, Peter C; Zelterman, Daniel; Scholz, Jodi A Carlson

    2011-07-01

    Naturally occurring diabetes mellitus (DM) is common in several species of Old and New World nonhuman primates. Fructosamine values provide important information about recent glycemic control and can be useful in the diagnosis and management of DM. However, despite an abundance of reports in the literature describing spontaneous and induced DM in monkeys, few reference ranges are available for fructosamine. Reference ranges have been published for woolly monkeys (Lagothrix lagotricha), cynomolgus macaques (Macaca fascicularis), and stumptail macaques (Macaca arctoides) but currently are not available for rhesus macaques. At our institution, DM is a common diagnosis in aging rhesus macaques. Here we report a reference range for fructosamine in rhesus macaques. The overall range was 157 to 230 μmol/L, with male rhesus and macaques 10 y or older having significantly higher values than do female rhesus and macaques younger than 10 y, respectively. This range provides clinical veterinarians with an additional tool for evaluating glycemic control in rhesus macaques. Copyright 2011 by the American Association for Laboratory Animal Science

  15. Innate-like γδ T cell responses to mycobacterium Bacille Calmette-Guerin using the public Vγ2 repertoire in Macaca fascicularis

    Science.gov (United States)

    Cairo, Cristiana; Hebbeler, Andrew M; Propp, Nadia; Bryant, Joseph L; Colizzi, Vittorio; Pauza, C. David

    2010-01-01

    The Vγ2Vδ2 T cell subset responds to Bacille Calmette-Guerin (BCG) immunization in macaques and may be a component of protective immunity against tuberculosis. We characterized the effects of BCG on the Vγ2Vδ2 T cell receptor repertoire by comparing the starting population of Vγ2 chains in cynomolgus macaques with the repertoire found after priming or booster immunization with BCG. The starting repertoire was dominated by public Vγ2 chain sequences that were found repeatedly among unrelated animals. Primary exposure to BCG triggered expansion of cells expressing public Vγ2 chains and booster immunization was often associated with contraction of these same subsets. Thus, BCG-reactive Vγ2 chains were present at high frequency in the repertoire of mycobacteria-naïve macaques and they comprised the major response to primary or booster immunization. Normal selection processes that created the naïve Vγ2 repertoire in macaques, also encoded the capacity for rapid responses to mycobacteria. The unusual composition of a normal Vγ2 repertoire helps to explain the powerful γδ T cell responses to BCG immunization. PMID:17292671

  16. Innate-like gammadelta T cell responses to mycobacterium Bacille Calmette-Guerin using the public V gamma 2 repertoire in Macaca fascicularis.

    Science.gov (United States)

    Cairo, Cristiana; Hebbeler, Andrew M; Propp, Nadia; Bryant, Joseph L; Colizzi, Vittorio; Pauza, C David

    2007-07-01

    The V gamma 2 V delta 2 T cell subset responds to Bacille Calmette-Guerin (BCG) immunization in macaques and may be a component of protective immunity against tuberculosis. We characterized the effects of BCG on the V gamma 2 V delta 2 T cell receptor repertoire by comparing the starting population of V gamma 2 chains in cynomolgus macaques with the repertoire found after priming or booster immunization with BCG. The starting repertoire was dominated by public V gamma 2 chain sequences that were found repeatedly among unrelated animals. Primary exposure to BCG triggered expansion of cells expressing public V gamma 2 chains and booster immunization was often associated with contraction of these same subsets. Thus, BCG-reactive V gamma 2 chains were present at high frequency in the repertoire of mycobacteria-naïve macaques and they comprised the major response to primary or booster immunization. Normal selection processes that created the naïve V gamma 2 repertoire in macaques, also encoded the capacity for rapid responses to mycobacteria. The unusual composition of a normal V gamma 2 repertoire helps to explain the powerful gammadelta T cell responses to BCG immunization.

  17. Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data

    Science.gov (United States)

    Peng, Xinxia; Pipes, Lenore; Xiong, Hao; Green, Richard R.; Jones, Daniel C.; Ruzzo, Walter L.; Schroth, Gary P.; Mason, Christopher E.; Palermo, Robert E.; Katze, Michael G.

    2014-01-01

    Background The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. Methods We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. Results For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely ‘missing’ from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. Conclusions For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies. PMID:24810475

  18. Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification.

    Directory of Open Access Journals (Sweden)

    Sajid Javed

    Full Text Available A temporal study of gene expression in peripheral blood leukocytes (PBLs from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an 'early' FOS-associated response, to a 'late' predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using

  19. Pathogenesis of fulminant monkeypox with bacterial sepsis after experimental infection with West African monkeypox virus in a cynomolgus monkey.

    Science.gov (United States)

    Nagata, Noriyo; Saijo, Masayuki; Kataoka, Michiyo; Ami, Yasushi; Suzaki, Yuriko; Sato, Yuko; Iwata-Yoshikawa, Naoko; Ogata, Momoko; Kurane, Ichiro; Morikawa, Shigeru; Sata, Tetsutaro; Hasegawa, Hideki

    2014-01-01

    The pathogenesis of severe human monkeypox, which causes systemic and fulminant infections, is not clear. This study presents a case repot of fulminant monkeypox with bacterial sepsis after experimental infection with monkeypox virus in a cynomolgus monkey (Macaca fascicularis). In our previous study (Saijo et al., 2009, J Gen Virol), two cynomolgus monkeys became moribund after experimental infection with monkeypox virus Liberia strain, West African strain. One exhibited typical monkeypox-related papulovesicular lesions. The other monkey presented fulminant clinical symptoms with a characteristic flat red rash similar to that found in smallpox, which is associated with extremely high fatality rates. In this study, we found that the monkey with flat red rash had high levels of viremia and neutropenia, as well as high plasma levels of pro-inflammatory cytokines and chemokines compared with the other monkey. Monkeypox virus replicates in epithelial cells and macrophages in various organs. Sepsis due to Gram-positive cocci was confirmed histopathologically in the monkey with flat red rash. The lack of inflammatory response in the lesion suggested that the monkey with sepsis experienced strong immune suppression during the viral infection. The neutropenia and excessive inflammatory cytokine responses indicate that neutrophils play key roles in the pathogenesis of systemic and fulminant human monkeypox virus infections with sepsis.

  20. 利用微卫星标记分析4个食蟹猴群体的遗传多样性%Analysis of genetic diversity of four Macaca fascicularis populations with microsatellite markers

    Institute of Scientific and Technical Information of China (English)

    皮道元; 谢莉萍; 卢晟盛; 卢克焕

    2011-01-01

    利用7个恒河猴源微卫星标记和4个人源微卫星标记共11个标记,分析了来源于束埔寨(Pop1)、老挝(Pop2)、越南1(Pop3)和越南2(Pop4)共4个群体食蟹猴的遗传多样性.研究结果显示,所选择的11个微卫星位点表现出很高的多态性,群体内的多态性较低,存在较严重的近亲交配.Hardy-Weinberg平衡检测说明4个群体在这11个位点上均处于不平衡状态,可能存在较严重的人工选择繁育.亚群体内的固定指数平均为0.526 2,说明群体内存在近亲交配;亚种群间的固定指数均值为0.016 6,说明各群体间的遗传分化很小;各位点上的基因流均值为14.814 2,说明其交流很活跃,可有效地防止因遗传漂移而产生的遗传分化.从基于Nei氏标准遗传距离的UPGMS聚类图看出,先是Pop3和Pop4聚为一类,再和Pop1聚在一起,最后和Pop2聚在一起,其结果和其地理分布所表现的遗传差异一致.%The genetic diversity of Macaca fascicularis from four populations was analyzed by using eleven microsatellite markers including seven rhesus-derived markers and four human-derived makers. The four populations came from Cambodia (Pop 1) ,Laos (Pop 2) ,Vietnam 1 (Pop 3) and Vietnam 2 (Pop 4) ,respectively. It is illuminated that the high polymorphism was showed in 11 microsatellite locus. There was low polymorphism and seriously inbreeding within the groups. The unbalance on 11 locus from four groups was proved according to Hardy-Weinberg test. There may be more serious artificial selection inbreeding. When Fis is 0. 526 2,it showed that inbreeding was existed within groups. The Fst is 0.016 6,meaning that the genetic differentiation between groups is very small. The gene flow on every locus is 14.814 2, showing that the exchange of them is active. It may be effective by preventing genetic from differentiation because of genetic drift. According to dendrogram of UPGMS based on Nei's Unbiased Measures of genetic distance,Pop3

  1. 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

  2. Investigation on Gastrointestinal Parasites in Captive-bred Macaca mulatta and Macaca fascicularis in Guangxi%广西地区人工驯繁猕猴、食蟹猴胃肠道寄生虫感染情况的初步调查

    Institute of Scientific and Technical Information of China (English)

    李健; 全琛宇; 施维; 周庆安; 张鸿满; 黄维义; 何国声

    2013-01-01

    Objective To understand the infection status of gastrointestinal parasites in captive-bred non-human primates (Macaca mulatta and Macaca fascicularis) in Guangxi,and provide basis for prevention and control strategies.Methods The monkeys were divided into three groups,the growth group,the breeding group,and the quarantine group.Totally 784 fresh feces samples from M.mulatta and M.fascicularis were collected at six monkey shelters in Guangxi,during 2008~2012.The direct smear method (DS),saturation salt solution float method (SSF) and formaldehyde-ether precipitation method (FEP) were used for fecal parasite examination under the microscope.Results The total infection rate was 72.4% among 784 sample.Five protozoan species Ameoba,Trichomonas sp.,Giardia sp.,Balantidium coli and Coccidia),five species of nematodes(Trichuris sp.,Streptopharagus sp.,Physaloptera sp.,Oesophagostmum sp.and Strongyloides sp.),two species of cestodas (Hymenolepis sp.and Bertiella studeri),one speice of trematoda and one speice of arthropod were identified.The gastrointestinal parasites infection of the growth group was possessed of the fewest among three groups,while the quarantine group was the largest.Relatively higher prevalence of protozoan was observed in both the growth monkey group and the breeding group,and the highest infection rate was found in both Amoeba and B.coli.Conclusions The results suggest that the protozoans with simple lifecycle and the soil transmitted nematodes which are difficult to kill by antihelmintic products nowadays,have become the major parasitic species that does serious harm to the captive-bred monkeys for experiment used in Guangxi.Herein,the infestation status could provide reference for prevention and controling strategies on parasitic disease of monkeys.Some species identified from this study have been considered as the pathogens of zoonose,which will have important public sanitation significances of countermeasure on disease spread between humans and

  3. Synaptic connectivity of the cholinergic axons in the olfactory bulb of the cynomolgus monkey

    Directory of Open Access Journals (Sweden)

    Teresa eLiberia

    2015-03-01

    Full Text Available The olfactory bulb of mammals receives cholinergic afferents from the horizontal limb of the diagonal band of Broca. At present, the synaptic connectivity of the cholinergic axons on the circuits of the olfactory bulb has only been investigated in the rat. In this report, we analyze the synaptic connectivity of the cholinergic axons in the olfactory bulb of the cynomolgus monkey (Macaca fascicularis. Our aim is to investigate whether the cholinergic innervation of the bulbar circuits is phylogenetically conserved between macrosmatic and microsmatic mammals. Our results demonstrate that the cholinergic axons form synaptic contacts on interneurons. In the glomerular layer, their main targets are the periglomerular cells, which receive axo-somatic and axo-dendritic synapses. In the inframitral region, their main targets are the granule cells, which receive synaptic contacts on their dendritic shafts and spines. Although the cholinergic boutons were frequently found in close vicinity of the dendrites of principal cells, we have not found synaptic contacts on them. From a comparative perspective, our data indicate that the synaptic connectivity of the cholinergic circuits is highly preserved in the olfactory bulb of macrosmatic and microsmatic mammals.

  4. 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.

  5. The Effects of TCDD on Pregnant Cynomolgus Macaque (MacacaFascicularis) and its Pregnancy Outcome%TCDD对猕猴妊娠期及其妊娠结局的毒性影响

    Institute of Scientific and Technical Information of China (English)

    郭玉梅; Lasley,B

    2000-01-01

    在雌猴妊娠第12天采用灌胃法一次性给予TCDD,剂量为1.0、2.0、4.0μg/kg.bw,每个剂量组4个动物。对照组(7个动物)给予相同体积的溶媒(丙酮-色拉油)。结果发现母猴在染毒10天后相继出现食欲下降、体重降低、脱毛、皮炎和贫血等中毒症状,染毒组12只猴子有10只在怀孕的第22到32天发生早期胚胎丢失。结果表明,低剂量TCDD可导致妊娠期猕猴出现中毒症状,并影响妊娠结局。%Females macaques were administrated single doses of 1, 2,4pg/kg TCDD(n = 4 per dose group)on gestational day (GD)12.The controls(n = 7)received the same dosing volume of acetone-coin oil. The results showed that poor appetite, weight loss, alope-cia, dermatitis, anemia and other toxic reactions were recordedsince rtrteatment day 10, and early fetal loss occurred between GDs22 and 32 in 10 of the 12 animals treated, with TCDD. The resultsdemonstrated that toxicity was induced by low level TCDD inpregnant macaques and pregnancy outcomes were affected too.

  6. Discrimination of Stem Cell Status after Subjecting Cynomolgus Monkey Pluripotent Stem Cells to Naïve Conversion

    Science.gov (United States)

    Honda, Arata; Kawano, Yoshihiro; Izu, Haruna; Choijookhuu, Narantsog; Honsho, Kimiko; Nakamura, Tomonori; Yabuta, Yukihiro; Yamamoto, Takuya; Takashima, Yasuhiro; Hirose, Michiko; Sankai, Tadashi; Hishikawa, Yoshitaka; Ogura, Atsuo; Saitou, Mitinori

    2017-01-01

    Experimental animal models have played an indispensable role in the development of human induced pluripotent stem cell (iPSC) research. The derivation of high-quality (so-called “true naïve state”) iPSCs of non-human primates enhances their application and safety for human regenerative medicine. Although several attempts have been made to convert human and non-human primate PSCs into a truly naïve state, it is unclear which evaluation methods can discriminate them as being truly naïve. Here we attempted to derive naïve cynomolgus monkey (Cm) (Macaca fascicularis) embryonic stem cells (ESCs) and iPSCs. Several characteristics of naïve Cm ESCs including colony morphology, appearance of naïve-related mRNAs and proteins, leukaemia inhibitory factor dependency, and mitochondrial respiration were confirmed. Next, we generated Cm iPSCs and converted them to a naïve state. Transcriptomic comparison of PSCs with early Cm embryos elucidated the partial achievement (termed naïve-like) of their conversion. When these were subjected to in vitro neural differentiation, enhanced differentiating capacities were observed after naïve-like conversion, but some lines exhibited heterogeneity. The difficulty of achieving contribution to chimeric mouse embryos was also demonstrated. These results suggest that Cm PSCs could ameliorate their in vitro neural differentiation potential even though they could not display true naïve characteristics. PMID:28349944

  7. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units. This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation and low to moderate doses (103 to 106 plaque forming units of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common influenza

  8. Induction and inhibition of cytochrome P450 1A1 and ethoxyresorufin-O-deethylation activity by polybrominated diphenyl ethers (PBDEs) in cynomolgus monkey primary hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peters, L.; Sanderson, J.T.; Berg, M. van den [Utrecht Univ. (Netherlands). Inst. for Risk Assessment Sciences; Bergman, A. [Stockholm Univ. (Sweden). Dept. of Environmental Chemistry

    2004-09-15

    Brominated flame retardants (BFRs) make up for 39% of the worldwide flame-retardants market. One groups of BFR, Polybrominated diphenylethers (PBDEs) are used as additive flameretardants in plastic materials, paints, and textile fabrics. Some PBDEs have been found to be lipophilic and persistent, and consequently bioaccumulate. Recently, levels of some PBDEs have been increasing in fish, wildlife, and in human tissue. The structural similarity of certain PBDE congeners to other polyhalogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs) has raised concerns that these compounds might act as agonists for the aryl hydrocarbon receptor (AhR). If some of these PBDEs were to act as Ah receptor agonists, they would warrant inclusion in the toxic equivalence factor (TEF) concept. CYP1A1 is a cytochrome P450 (CYP) enzyme that is involved in phase 1 biotransformation of xenobiotics and endogenous compounds such as estrogens. Many CYP enzymes detoxify xenobiotics or bioactivate xenobiotics to reactive intermediates. Although CYP1A1 is expressed in all mammals, there are differences in expression levels among species and tissues. To study the possible dioxin-like effects of environmentally most relevant PBDEs (BDE47, 77, 99, 100, 153, 154, 183, 209), the Ah receptor-mediated induction CYP1A1 was studied in cynomolgus monkey (Macaca fascicularis) primary hepatocytes. CYP 1A1 is the major enzyme that catalyses the deethylation of 7-ethoxyresorufin to resorufin. This ethoxyresorufin-Odeethylation (EROD) activity was used as a marker for CYP1A1 activity.

  9. Spontaneous obesity-linked type 2 diabetes in the absence of islet amyloid in a cynomolgus monkey infected with bovine spongiform encephalopathy.

    Science.gov (United States)

    Strom, A; Yutzy, B; Kruip, C; Völker, I; Schloot, N C; Roden, M; Scott, F W; Löwer, J; Holznagel, E

    2013-09-01

    A 9-year-old cynomolgus monkey (Macaca fascicularis) infected orally with bovine spongiform encephalopathy (BSE) was presented for necropsy following euthanasia 4 years post infection (p.i.). This macaque R984 was exposed to a BSE dose that causes a simian form of variant Creutzfeldt-Jakob disease (vCJD) within 5 years p.i. in other macaques. All orally BSE-infected macaques developed a significant weight gain within the first 2 years p.i. compared with non-BSE-infected age- and sex-matched control animals, suggesting increased risk of type 2 diabetes (T2D). In contrast, macaque R984 developed rapid weight loss, hyperglycemia, and glucosuria and had to be euthanatized 4 years p.i. before clinical signs of vCJD. Pancreas histopathological evaluation revealed severe islet degeneration but, remarkably, no islet amyloid deposits were present. Immunostaining of pancreas sections for insulin and glucagon confirmed the loss of endocrine cells. In addition, prions were present in the adenohypophysis but not in other areas of the brain, indicating centripetal prion spread from the gut during the preclinical phase of BSE infection. Plasma glucose and insulin concentrations of macaque R984 became abnormal with age and resembled T2D. This unusual case of spontaneous T2D in the absence of islet amyloid deposits could have been due to early prion spread from the periphery to the endocrine system or could have occurred spontaneously.

  10. In vitro germ cell differentiation from cynomolgus monkey embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kaori Yamauchi

    Full Text Available BACKGROUND: Mouse embryonic stem (ES cells can differentiate into female and male germ cells in vitro. Primate ES cells can also differentiate into immature germ cells in vitro. However, little is known about the differentiation markers and culture conditions for in vitro germ cell differentiation from ES cells in primates. Monkey ES cells are thus considered to be a useful model to study primate gametogenesis in vitro. Therefore, in order to obtain further information on germ cell differentiation from primate ES cells, this study examined the ability of cynomolgus monkey ES cells to differentiate into germ cells in vitro. METHODS AND FINDINGS: To explore the differentiation markers for detecting germ cells differentiated from ES cells, the expression of various germ cell marker genes was examined in tissues and ES cells of the cynomolgus monkey (Macaca fascicularis. VASA is a valuable gene for the detection of germ cells differentiated from ES cells. An increase of VASA expression was observed when differentiation was induced in ES cells via embryoid body (EB formation. In addition, the expression of other germ cell markers, such as NANOS and PIWIL1 genes, was also up-regulated as the EB differentiation progressed. Immunocytochemistry identified the cells expressing stage-specific embryonic antigen (SSEA 1, OCT-4, and VASA proteins in the EBs. These cells were detected in the peripheral region of the EBs as specific cell populations, such as SSEA1-positive, OCT-4-positive cells, OCT-4-positive, VASA-positive cells, and OCT-4-negative, VASA-positive cells. Thereafter, the effect of mouse gonadal cell-conditioned medium and growth factors on germ cell differentiation from monkey ES cells was examined, and this revealed that the addition of BMP4 to differentiating ES cells increased the expression of SCP1, a meiotic marker gene. CONCLUSION: VASA is a valuable gene for the detection of germ cells differentiated from ES cells in monkeys, and the

  11. The Establishment of Environmental Endocrine Disruptors Induced Precocious Puberty Macaca Fascicularis Model and the Intervention of Yin Nourishing Fire Purging Chinese Materia Medica%由环境内分泌干扰物引致食蟹猴性早熟疾病模型建立及滋阴泻火中药治疗干预的实验研究

    Institute of Scientific and Technical Information of China (English)

    朱琳; 蔡德培

    2012-01-01

    目的 建立灵长类--食蟹猴的由环境内分泌干扰物(environmental endocrine disruptors,EEDs)引致的性早熟疾病模型,验证滋阴泻火中药对EEDs拟雌激素活性的拮抗作用.方法 (1)不同月龄组青春前期雌性食蟹猴喂饲高、低剂量EEDs,通过观察EEDs拟雌激素作用,以确定最佳月龄、染毒剂量及染毒时间.(2)15只青春前期雌性食蟹猴随机分为染毒组、治疗组及对照组,每组5只.染毒组喂饲壬基酚(nonylphenol,4-NP)及双酚A(bisphenol,BPA),治疗组将染毒物质及滋阴泻火中药合剂同时喂饲,对照组喂饲溶剂玉米油.疗程4周.疗程完成时,检测血清雌激素水平、阴道脱落细胞成熟指数,取出子宫,测定其子宫湿重、子宫内膜及环形平滑肌厚度、子宫内膜上皮细胞及腺上皮细胞高度.结果 (1)20月龄为最佳染毒月龄,低剂量EEDs为最佳染毒剂量,4周为最佳染毒时间.(2)与对照组比较,染毒组血清雌激素水平明显升高,阴道脱落细胞成熟指数显著增加,子宫湿重、子宫内膜厚度及环形平滑肌厚度、子宫内膜上皮细胞及腺上皮细胞高度显著增加(P<0.05).与染毒组比较,治疗组上述指标均显著降低(P<0.05).结论 本研究成功地建立了灵长类--食蟹猴由EEDs引致性早熟的疾病模型,证实了EEDs具有显著的拟雌激素活性,并验证了滋阴泻火中药合剂对其拟雌激素活性具有显著的拮抗作用.%Objective To establish the environmental endocrine disruptors (EEDs) induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging Chinese materia medica (YNFPCMM) against the estrogenic effects. Methods (1) The female prepubescent monkeys at different months old were fed with high dose and low dose EEDs. By observing EEDs' estrogenic effects, the optimal age, the optimal exposure dose, and the optimal exposure time were determined. (2) Fifteen female prepubescent monkeys were

  12. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

    The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

  13. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

    The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

  14. Visuospatial properties of caudal area 7b in Macaca fascicularis

    Institute of Scientific and Technical Information of China (English)

    Hui-Hui JIANG; Ying-Zhou HU; Jian-Hong WANG; Yuan-Ye MA; Xin-Tian HU

    2013-01-01

    To proceed from sensation to movement,integration and transformation of information from different senses and reference frames are required.Several brain areas are involved in this transformation process,but previous neuroanatomical and neurophysiological studies have implicated the caudal area 7b as one particular component of this transformation system.In this study,we present the first quantitative report on the spatial coding properties of caudal area 7b.The results showed that neurons in this area had intermediate component characteristics in the transformation system; the area contained bimodal neurons,and neurons in this area encode spatial information using a hybrid reference frame.These results provide evidence that caudal area 7b may belong to the reference frame transformation system,thus contributing to our general understanding of the transformation system.

  15. Image collection: 44 [Togo Picture Gallery[Archive

    Lifescience Database Archive (English)

    Full Text Available 44 Macaca_fascicularis_NL.png カニクイザル Cynomolgus Macaca fascicularis 9541 生物アイコン,脊索動物門,脊椎動物亜門,哺乳綱,獣亜綱,真獣下綱,霊長目

  16. Particle-to-PFU Ratio of Ebola Virus Influences Disease Course and Survival in Cynomolgus Macaques

    Science.gov (United States)

    Alfson, Kendra J.; Avena, Laura E.; Beadles, Michael W.; Staples, Hilary; Nunneley, Jerritt W.; Ticer, Anysha; Dick, Edward J.; Owston, Michael A.; Reed, Christopher; Patterson, Jean L.; Carrion, Ricardo

    2015-01-01

    ABSTRACT This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (Macaca fascicularis) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease in vivo. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. IMPORTANCE Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically

  17. 中国食蟹猴脑磁共振图像模板的构建%Construction of MRI template of the chinese cynomolgus monkeys brain

    Institute of Scientific and Technical Information of China (English)

    李洁兰; 桑明; 林富春; 曾俊杰; 王勇; 鲜巧阳; 文之; 吴光耀; 霍文哲

    2014-01-01

    目的:建立中国食蟹猴脑结构T 1图像模板,分析其脑灰质、白质及脑脊液组织概率分布图。方法16只健康中国食蟹猴3.0T MRI脑的高分辨3D矢状位 T1WI采集,使用模糊C均值聚类(fuzzy c-meass clusteriag Algorithm , FCM )法对每例图像进行组织分割、插值、空间标准化及图像平滑,建立脑白质、灰质、脑脊液组织概率图和个体脑模板。对所得图像进行配准及平均后,再经过VBM流程分析测试获得食蟹猴M RI图像模板。结果建立了正常中国食蟹猴脑结构3D模板,并获得了食蟹猴脑白质、灰质、脑脊液三种组织的概率图,清晰地显示了全脑T1加权对比结构。结论建立M RI图像模板和组织概率图为中国食蟹猴脑结构VBM 分析和fM RI定位提供了重要的基础和便利。%Objective To establish a T1 image template of the Chinese cynomolgus monkeys (Macaca fascicularis) brain and to perform a analysis brain tissue by developing a digital multi-atlas of grey matter ,whiter matter and cerebrospinal fluid .Methods Sixteen healthy Chinese cynomolgus monkeys were scanned by high resolution 3 .0 T Magnatic Resonance Imaging (MRI) to acquire sagittal 3D T1WI images .An individual brain template and tissue digital atlases of grey matter was conducted ,white matter and cerebrospinal fluid ;segmentation ,interpolation ,spatial normalization and image smoot-hing of the MRIs were carried out using the Fuzzy c-means Clustering Algorithm (FCM) .When co-registration and an av-erage on the reference images were performed ,cynomolgus monkeys brain atlases was then constructed after voxel-based morphometry (VBM) process analysis and testing of the multi-atlas .Results The 3D MRI template of healthy Chinese cynomolgus monkeys was established three tissue digital atlases of grey matter ,white matter and cerebrospinal fluid were developed ,distinctly indicating the whole brain T1-weighted contrast structure .Conclusion

  18. Enhanced immunogenicity of a respiratory syncytial virus (RSV) F subunit vaccine formulated with the adjuvant GLA-SE in cynomolgus macaques.

    Science.gov (United States)

    Patton, Kathryn; Aslam, Shahin; Shambaugh, Cindy; Lin, Rui; Heeke, Darren; Frantz, Chris; Zuo, Fengrong; Esser, Mark T; Paliard, Xavier; Lambert, Stacie L

    2015-08-26

    Respiratory syncytial virus (RSV) causes significant disease in elderly adults, but an effective vaccine is not yet available. We have previously reported that vaccines consisting of engineered respiratory syncytial virus soluble fusion protein (RSV sF) adjuvanted with glucopyranosyl lipid A (GLA) in an oil-in-water emulsion (stable emulsion [SE]) induce RSV F-specific T and B cell responses in mice and rats that protect from viral challenge. Here, we evaluated the immunogenicity of GLA-SE adjuvanted RSV sF vs unadjuvanted RSV sF vaccines in cynomolgus macaques (Macaca fascicularis). RSV F-specific IgG, RSV neutralizing antibodies, and RSV F-specific T cell IFNγ ELISPOT responses induced by GLA-SE adjuvanted RSV sF peaked at week 6 at significantly higher levels than achieved by unadjuvanted RSV sF and remained detectable through week 24, demonstrating response longevity. Two weeks after a week 24 booster immunization, humoral and cellular responses reached levels similar to those seen at the earlier peak response. Importantly, the GLA-SE adjuvanted RSV sF vaccine induced cross-neutralizing antibodies to other RSV A and B strains as well as F-specific IgA and IgG memory B cells. GLA-SE adjuvanted RSV sF was also demonstrated to drive a Th1-biased response characterized by more IFNγ than IL-4. This study indicates that a GLA-SE adjuvanted RSV sF vaccine induces robust humoral and Th1-biased cellular immunity in non-human primates and may benefit human populations at risk for RSV disease.

  19. A macaque model for hantavirus infection.

    NARCIS (Netherlands)

    J. Groen (Jan); M.N. Gerding; J.P. Koeman; P.J.M. Roholl (Paul); G. van Amerongen (Geert); H.G.M. Jordans; A.D.M.E. Osterhaus (Albert); H.G.M. Niesters (Bert)

    1995-01-01

    textabstractCynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hallnas), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild pro

  20. Detection of Early Atherosclerosis in M. Fascicularis with Transcutaneous Ultrasonic Measurement of the Elastic Properties of the Common Carotid Artery

    OpenAIRE

    Farrar, David J; Riley, Ward A.; Bond, M Gene; Barnes, Ralph N.; Love, L. Alan

    1982-01-01

    The elastic properties of 22 common carotid arteries from 13 male cynomolgus monkeys (M. fascicularis) that were fed either a high cholesterol (test) diet or a standard monkey chow (control) diet for 18 months were measured noninvasively with 5MHz ultrasound. A B-mode image of the artery was obtained with a 32-element linear array transducer, and a single line of video ultrasonic information was selected for tracking the echoes from the adventitial side of the near wall to the lumen-intima in...

  1. Evaluation of Serum Lipid, Thyroid, and Hepatic Clinical Chemistries in Association With Serum Perfluorooctanesulfonate (PFOS) in Cynomolgus Monkeys After Oral Dosing With Potassium PFOS

    Science.gov (United States)

    Allen, Bruce C.; Andres, Kara L.; Ehresman, David J.; Falvo, Ria; Provencher, Anne; Olsen, Geary W.; Butenhoff, John L.

    2017-01-01

    Abstract An oral dose study with perfluorooctanesulfonate (PFOS) was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fascicularis). In this study, control group (n = 6/sex) was sham-dosed with vehicle (0.5% Tween 20 and 5% ethanol in water), low-dose group (n = 6/sex) received 1 single K+PFOS dose (9 mg/kg), and high-dose group (n = 4–6/sex) received 3 separate K+ PFOS doses (11–17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior to, during, and after K+PFOS administration for up to 1 year and they were analyzed for PFOS concentrations and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 μg/ml. When compared with time-matched controls, administration of K+PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the high-density lipoprotein fraction), although not toxicologically significant, was observed. The corresponding lower-bound fifth percentile benchmark concentrations (BMCL1sd) were 74 and 76 μg/ml for male and female monkeys, respectively. Compared to the 2013–2014 geometric mean serum PFOS level of 4.99 ng/ml (0.00499 μg/ml) in US general population reported by CDC NHANES, this represents 4 orders of magnitude for margin of exposure. PMID:28115654

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

    Science.gov (United States)

    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.

  3. Kadar Kolesterol Monyet Ekor Panjang (Macaca Fascicularis Obesitas di Pura Uluwatu Bali

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Ratna Wulan Sari

    2016-08-01

    Full Text Available Penelitian deskriptif-observasional dengan pendekatan cross-sectional telah dilakukan untuk mengetahui kadar kolesterol total monyet ekor panjang obesitas yang hidup liar di Pura Luhur Uluwatu, Bali. Sebanyak enam belas monyet ekor panjang berhasil ditangkap bius menggunakan ketamin dosis 10 mg/kg berat badan dicampur dengan premedikasi xylazin dosis 1-2 mg/kg berat badan, kemudian dilakukan pemeriksaan kesehatan, pengukuran morfometri dan pengambilan sampel darah. Penentuan kadar kolesterol menggunakan mesin automatic chemistry analyzer by Indiko- Thermo Scientific. Dari 16 ekor monyet, 12 ekor tergolong obesitas berdasarkan Indeks Masa Tubuh dan Berat Badan (IMT ?32,81±1,1 kg/m2 menurut Putra et al. (2006; BB ?8 kg. Hasil penelitian menunjukkan rataan kadar kolesterol total monyet obesitas adalah 107,75 ml/dL. Dari hasil penelitian dapat disimpulkan bahwa kadar kolesterol monyet ekor panjang obesitas di Pura Uluwatu, Bali masih normal.

  4. Aging, dominance history, and social behavior in Java-monkeys (Macaca fascicularis)

    NARCIS (Netherlands)

    Gispen, W.H.; Veenema, H.C.; Spruijt, B.M.; Vanhooff, J.A.R.A.M.

    1997-01-01

    The aim of this study was to investigate the influence of the dominance history of socially housed Java-monkeys on the aging process. In monkeys, social subordinance is generally associated with elevated levels of cortisol, which, in turn, have been suggested to influence cognitive decline. As cogni

  5. Entamoeba histolytica and E. dispar infections in captive macaques (Macaca fascicularis) in the Philippines.

    Science.gov (United States)

    Rivera, Windell L; Yason, John Anthony D L; Adao, Davin Edric V

    2010-01-01

    Entamoeba histolytica is a protozoan parasite that infects man and animals. This parasite has a global distribution and the disease it causes is usually characterized by diarrhea. In order to detect the parasite, it is necessary to differentiate it from Entamoeba dispar. E. dispar appears morphologically similar to E. histolytica but does not cause disease and tissue invasion. This study reports on the prevalence of E. histolytica and E. dispar among captive macaques in a primate facility in the Philippines. PCR was used to correctly identify both Entamoeba species. Indirect fluorescent antibody test (IFAT) was also performed to determine the seroprevalence of amebiasis in the captive macaques. Based on PCR targeting of the peroxiredoxin gene, of the 96 stool samples collected, 23 (24%) contained E. histolytica while 32 (33%) contained E. dispar. IFAT revealed 26 (27%) serum samples positive for antibodies against E. histolytica. Sequence analysis of the 18S rRNA gene showed that the 23 E. histolytica isolates were identical to human E. histolytica isolates deposited in the GenBank and not Entamoeba nuttalli as found in macaques in other recent reports. The Philippines is a major exporter of monkeys for biomedical research purposes, so screening animals before transporting them to other locations lessens the risk of spreading zoonoses to a wider area. This is the first report of the molecular detection of E. histolytica and E. dispar among macaques in the Philippines. This study complements the limited information available on the animal hosts of E. histolytica in the Philippines.

  6. Structural and functional definition of the motor cortex in the monkey (Macaca fascicularis).

    Science.gov (United States)

    Sessle, B J; Wiesendanger, M

    1982-02-01

    1. The details of the organization of the motor cortex and its anterior and posterior border were investigated in three monkeys by a combination of techniques including intracortical microstimulation (i.c.m.s.), electrophysiological recording of cutaneous and muscle afferent inputs to single cortical neurones, and electrophysiological and anatomical identification of corticospinal neurones; in addition, data from these methods were related to cortical cytoarchitecture.2. Almost 5000 individual cortical loci were tested with i.c.m.s. in the unanaesthetized monkeys. In this paper, we particularly consider the organization of the forelimb motor representation, and its relation to the representation of other parts of the body. I.c.m.s. thresholds of about 5 muA were common for evoking twitch movements and e.m.g. responses in distal forelimb and face, jaw and tongue muscles, but proximal forelimb, trunk and hind-limb movements also sometimes had such low thresholds.3. The fingers were found to be represented nearest the central sulcus, with horseshoe-shaped bands of cortical tissue representing progressively more proximal muscles situated around this central ;finger core'.4. Cytoarchitectonically, the cortex having these low-threshold motor effects was characteristic of area 4. There was also a close fit between the extent of this ;excitable cortex' and the extent of densely spaced corticospinal neurones identified electro-physiologically or with horseradish peroxidase labelling. In subsequent mapping of forelimb afferents to the cortex when the animal was deeply anaesthetized, low-threshold and short-latency responses to muscle nerve stimulation were rarely found in this ;excitable cortex'.5. The anterior border could be clearly established by i.c.m.s. and by the sharp boundary of corticospinal neurones. It was noted that the motor cortex extends rostrally beyond area 4 and its anterior border appears to reside in the posterior part of area 6aalpha (Vogt & Vogt, 1919) although it is difficult to establish the precise transition from area 4 to area 6.6. Posteriorly, the ;micro-excitable cortex' was found to be limited to regions cytoarchitectonically delineated as area 4 and did not include area 3a. On the other hand, low-threshold forelimb proprioceptive afferent inputs appeared restricted to area 3a neurones in the deeply anaesthetized animal. Corticospinal neurones were very dense in area 4, and there was a clear decrease in their occurrence in more caudal areas. However, scattered nests of corticospinal neurones were noted in areas 3a, 3b, 2, 1 and 5. It remains to be seen whether these scattered nests could be directly involved in motor control or whether they may modulate ascending somatosensory transmission, and whether they rely on sensory feed-back or inputs from other central areas for their spinal effects.

  7. Increased rigidity with age in social behavior of Java-monkeys (Macaca fascicularis)

    NARCIS (Netherlands)

    Veenema, H.C.; Hooff, van J.A.R.A.M.; Gispen, W.H.; Spruijt, B.M.

    2001-01-01

    In this study we investigated the effect of aging on the structure of behavior of socially housed Java-monkeys. Indices of the sequential structure of an animal's own ongoing behavior and of its responses to behavior of other animals were calculated using an information statistic approach. These ind

  8. Characterization of PrPc-immunoreactive cells in monkey (Macaca fascicularis) gastrointestinal tract.

    Science.gov (United States)

    Marcos, Z; Bodegas, M E; Sesma, M P; Guembe, L

    2005-04-01

    The gastrointestinal tract (GIT) is one of the most likely entry sites for the pathological isoform of prions (PrP(sc)). To understand how PrP(sc) crosses the digestive mucosa, it is crucial to characterize the cells expressing normal prion protein (PrP(c)). By means of double immunofluorescence applied to sections of the monkey GIT, we demonstrated that, in the stomach, PrP(c) immunostaining occurs in subsets of histamine, somatostatin (Som), ghrelin (Ghr), gastrin (G), and serotonin (5HT) cells. In the small and large bowels, PrP(c) cells were found in subpopulations of cells immunolabeled for 5HT, Som, G, and peptide YY (PYY).

  9. The mechanical significance of the temporal fasciae in Macaca fascicularis: an investigation using finite element analysis.

    Science.gov (United States)

    Curtis, Neil; Witzel, Ulrich; Fitton, Laura; O'higgins, Paul; Fagan, Michael

    2011-07-01

    Computational finite element analyses (FEAs) of the skull predict structural deformations under user specified loads and constraints, with results normally presented as stress and strain distributions over the skull's surface. The applied loads are generally a representation of the major adductor musculature, with the skull constrained at bite positions and at the articulating joints. However, virtually all analyses ignore potentially important anatomical structures, such as the fasciae that cover the temporalis muscle and attach onto the zygomatic arch. In vivo experimental studies have shown that removal of the temporal fasciae attachment onto the zygomatic arch in Cebus monkeys results in significant bone adaptation and remodeling in this region, suggesting the fasciae play an important role in stabilising the arch during biting. Here we investigate this potential stabilising role by carrying out FEAs of a macaque skull with and without temporal fasciae included. We explore the extent to which the zygomatic arch might be stabilized during biting by a synchronized tensioning of the temporal fasciae, acting to oppose masseteric contraction forces. According to our models, during temporalis muscle bulging the forces generated within the tensioned temporal fasciae are large enough to oppose the pull of the masseter. Further, a near bending-free state of equilibrium within the arch can be reached, even under forceful biting. We show that it is possible to eliminate the high strain gradients in and around the zygomatic arch that are present in past computational studies, with strains being more uniform in magnitude than previously thought.

  10. Increased rigidity with age in social behavior of Java-monkeys (Macaca fascicularis)

    NARCIS (Netherlands)

    Veenema, H.C.; Hooff, van J.A.R.A.M.; Gispen, W.H.; Spruijt, B.M.

    2001-01-01

    In this study we investigated the effect of aging on the structure of behavior of socially housed Java-monkeys. Indices of the sequential structure of an animal's own ongoing behavior and of its responses to behavior of other animals were calculated using an information statistic approach. These ind

  11. The relationship between masseter force and masseter electromyogram during mastication in the monkey Macaca fascicularis.

    Science.gov (United States)

    Hylander, W L; Johnson, K R

    1989-01-01

    In five adult monkeys, electromyograms (EMGs) were recorded from bipolar surface electrodes positioned over the superficial masseter and from bipolar fine-wire electrodes within both the superficial and deep masseter. Relative masseter force was estimated by measuring surface bone strain from the lateral aspect of the zygomatic arch using rosette strain gauges. Multiple step-wise regression procedures demonstrated that peak values of the averaged masseter EMG could often explain a considerable amount of the variation of peak relative masseter force during mastication, i.e. r2 values ranged from 0.23 to 0.96 for the various single-electrode models and R2 values ranged from 0.78 to 0.96 for the various multiple-electrode models. The r2 values for relative masseter force and EMG data from the surface electrodes ranged from 0.69 to 0.96, and, on average, EMG data from surface electrodes provided somewhat more information about overall relative muscle force than data from fine-wire electrodes. The R2 values for a two-electrode model, consisting of data from surface electrodes over the superficial masseter and fine-wire electrodes in the posterior portion of the deep masseter, ranged from 0.78 to 0.95. The latency between the averaged surface EMG and relative muscle force was determined and the data indicated that the surface EMG usually preceded muscle force. This latency tended to decrease gradually throughout the entire power stroke of mastication. At peak values, the surface EMG preceded muscle force by about 22 ms. Towards the end of the power stroke, i.e. the 25% of peak values during unloading, muscle force may actually precede the average EMG.

  12. Reach–to-grasp movements in macaca fascicularis monkeys: the Isochrony Principle at work

    Directory of Open Access Journals (Sweden)

    Luisa eSartori

    2013-03-01

    Full Text Available Humans show a spontaneous tendency to increase the velocity of their movements depending on the linear extent of their trajectory in order to keep execution time approximately constant. Termed the isochrony principle, this compensatory mechanism refers to the observation that the velocity of voluntary movements increases proportionally with their linear extension. Although there is a wealth of psychophysical data regarding isochrony in humans, there is none regarding non-human primates. The present study attempts to fill that gap by investigating reach-to-grasp movement kinematics in free-ranging macaques. Video footage of monkeys grasping objects located at different distances was analyzed frame-by-frame using digitalization techniques. The amplitude of arm peak velocity was found to be correlated with the distance to be covered, and total movement duration remained invariant although target distances varied. Like in humans, the ‘isochrony principle’ seems to be operative as there is a gearing down/up of movement velocity that is proportional to the distance to be covered in order to allow for a relatively constant movement duration. Based on a centrally generated temporal template, this mode of motor programming could be functional in macaques given the high speed and great instability of posture and joint kinematics characterizing their actions. The data presented here take research in the field of comparative motor control a step forward as they are based on precise measurements of spontaneous grasping movements by animals living/acting in their natural environment.

  13. Monitoring gene expression in muscle tissue of macaca fascicularis under the influence of testosterone and SARM.

    Science.gov (United States)

    Reiter, Martina; Tichopad, Ales; Riedmaier, Irmgard; Pfaffl, Michael W; Meyer, Heinrich H D

    2010-01-01

    The focus of this study was to evaluate data on the gene expression profiles induced by testosterone and a selective androgen receptor modulator (SARM, TAP Pharmaceutical Products Inc., Lake Forest, IL, USA) in androgen sensitive muscle tissue to obtain a better understanding on the molecular mechanisms of action and to identify biomarkers for SARM function in primate organs. A total of 24 male cyomolgus monkeys were divided into four groups: testosterone group, SARM1 group, SARM10 group, and control group, each consisting of six animals. The testosterone group was treated i.m. with 3.0 mg/kg Testostoviron®-depot-250 (Schering, Berlin, Germany) every 2 weeks, the SARM1 and SARM10 groups with 1 mg/kg or 10 mg/kg SARM LGD2941 daily, and the control group was not treated. Muscle biopsies from musculus quadriceps and musculus triceps were collected at three time points: baseline time point before SARM application (control), on day 16, and on day 90 of treatment. A total of 30 candidate genes were selected according to their functionality by screening the actual literature and were composed to the following functional groups: cell cycle, endocrine factors, energy metabolism, muscle fiber proteins, muscle specific transcription factors, protein metabolism, and satellite cell biology. Biomarkers were identified as genes regulated from baseline in any of the three treatment groups at day 16 or day 90 using analysis of variance with baseline defined as the contrast group. Out of 23 tested candidate genes, 3 were significantly regulated in m. quadriceps after 90 days treatment; in m. triceps no significant differences were identified. Cathepsin L, calpain 3, and insulin like growth factor binding protein 3 could be identified as first biomarkers, and first physiological differences between control and treatment samples were determined. Both testosterone and SARM LGD2941 appear to have similar effects after 90 days treatment, and thus a longer-term therapy with these substances can be recommended.

  14. Reticulospinal neurons in the pontomedullary reticular formation of the monkey (Macaca fascicularis).

    Science.gov (United States)

    Sakai, S T; Davidson, A G; Buford, J A

    2009-11-10

    Recent neurophysiological studies indicate a role for reticulospinal neurons of the pontomedullary reticular formation (PMRF) in motor preparation and goal-directed reaching in the monkey. Although the macaque monkey is an important model for such investigations, little is known regarding the organization of the PMRF in the monkey. In the present study, we investigated the distribution of reticulospinal neurons in the macaque. Bilateral injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were made into the cervical spinal cord. A wide band of retrogradely labeled cells was found in the gigantocellular reticular nucleus (Gi) and labeled cells continued rostrally into the caudal pontine reticular nucleus (PnC) and into the oral pontine reticular nucleus (PnO). Additional retrograde tracing studies following unilateral cervical spinal cord injections of cholera toxin subunit B revealed that there were more ipsilateral (60%) than contralateral (40%) projecting cells in Gi, while an approximately 50:50 ratio contralateral to ipsilateral split was found in PnC and more contralateral projections arose from PnO. Reticulospinal neurons in PMRF ranged widely in size from over 50 microm to under 25 microm across the major somatic axis. Labeled giant cells (soma diameters greater than 50 microm) comprised a small percentage of the neurons and were found in Gi, PnC and PnO. The present results define the origins of the reticulospinal system in the monkey and provide an important foundation for future investigations of the anatomy and physiology of this system in primates.

  15. Antibody Responses in the Nonhuman Primate, Macaca Fascicularis, to Protein Toxins

    Science.gov (United States)

    1990-05-01

    your husband’s "educational experiences". And to my greatest of all r’-ildren in the world, Sarah and Jonathan, who did their best to understand when...Monogr Allergy 19:122-133. 118 Hammarstrom, L., Lefranc, G., Lefranc, M.P., Persson, MAA . Smith, C.I.E. 1986. Aberrant pattern of anti-carbohydrate

  16. Aerosol measles vaccination in macaques: Preclinical studies of immune responses and safety

    NARCIS (Netherlands)

    R.L. de Swart (Rik); T. Kuiken (Thijs); J. Fernandez-de Castro (Jorge); M.J. Papania (Mark); J.V. Bennett (John); J.L. Valdespino (José); P.D. Minor; C.L. Witham (Clyde); S. Yüksel (Selma); H.W. Vos (Helma); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

    2006-01-01

    textabstractThe comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different r

  17. Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009 (Morbidity and Mortality Weekly Report. Volume 59, Number RR-6, July 23, 2010)

    Science.gov (United States)

    2010-07-23

    et al. Pathology of inhalation anthrax in cynomolgus monkeys (Macaca fascicularis). Lab Invest 2003;83:1201–9. 113. Stearns- Kurosawa DJ, Lupu F...Taylor Jr FB, Kinasewitz G, Kurosawa S. Sepsis and pathophysiology of anthrax in a nonhuman primate model. Am J Pathol 2006;169:433–44. 114

  18. UniProt search blastx result: AK288787 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK288787 J090069N24 Q4R538|TBA1B_MACFA Tubulin alpha-1B chain (Tubulin alpha-ubiquitous... chain) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) - Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey) 0 ...

  19. A macaque model for hantavirus infection

    NARCIS (Netherlands)

    Groen, J; Gerding, M; Koeman, J P; Roholl, P J; van Amerongen, G; Jordans, H G; Niesters, H G; Osterhaus, A D

    1995-01-01

    Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hällnäs), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and

  20. The aetiology of SARS: Koch's postulates fulfilled

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); T. Kuiken (Thijs)

    2004-01-01

    textabstractProof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (Macaca, fascicularis). SARS-CoV-infected

  1. Viral replication and development of specific immunity in macaques after infection with different measles virus strains.

    NARCIS (Netherlands)

    R.S. van Binnendijk (Rob); R.W.J. van der Heijden (Roger); G. van Amerongen (Geert); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1994-01-01

    textabstractCynomolgus monkeys (Macaca fascicularis) were experimentally infected with a wild type measles virus (MV) strain (MV-BIL). Following intratracheal inoculation with different infectious doses, the virus could be isolated from peripheral blood mononuclear cells (PBMC), lung lavage cells, a

  2. Effect of cold and warm ischaemia on drug metabolism in isolated hepatocytes and slices from human and monkey liver

    NARCIS (Netherlands)

    Olinga, Peter; Hof, I.H; de Jager, M.H; de Jong, Kurt; Slooff, M.JH; Meijer, D.K F; Groothuis, Geny; Merema, M.T.

    1998-01-01

    1. The influence of short-term cold storage in University of Wisconsin organ preservation solution (UW) on the ability to metabolize lidocaine, testosterone and 7-ethoxycoumarin in isolated human and cynomolgus monkey (Macaca fascicularis) hepatocytes and liver slices has been investigated. 2. The h

  3. An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques

    Science.gov (United States)

    Sharpe, S. A.; White, A. D.; Sibley, L.; Gleeson, F.; Hall, G. A.; Basaraba, R. J.; McIntyre, A.; Clark, S. O.; Gooch, K.; Marsh, P. D.; Williams, A.; Dennis, M. J.

    2017-01-01

    Background New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. Methods Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. Results All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques Conclusions The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis. PMID:28273087

  4. Phylogenetic relationships of Malaysia's pig-tailed macaque Macaca nemestrina based on D-loop region sequences

    Science.gov (United States)

    Abdul-Latiff M. A., B.; Ampeng, A.; Yaakop, S.; Md-Zain B., M.

    2014-09-01

    Phylogenetic relationships among Malaysian pig-tailed macaques have never been established even though the data are crucial in aiding conservation plan for the species. The aims of this study is to establish the phylogenetic relationships of Macaca nemestrina in Malaysia. A total of 21 genetic samples of M. nemestrina yielding 458 bp of D-loop sequences were used in phylogenetic analyses, in addition to one sample of M. fascicularis which was used as an outgroup. Sequence character analysis revealed that D-loop locus contains 23% parsimony informative character detected among the ingroups. Further analysis indicated a clear separation between populations originating from different regions; the Malay Peninsula populations are separated from Borneo Insular population; and Perak population formed a distinctive clade within Peninsular Malaysia populations. Phylogenetic trees (NJ, MP and Bayesian) portray a consistent clustering paradigm as Borneo population was distinguished from Peninsula population (100% bootstrap value in the NJ, MP, 1.00 posterior probability in Bayesian trees). Perak's population was separated from other Peninsula populations (100% in NJ, 99% in MP and 1.00 in Bayesian). D-loop region of mtDNA is proven to be a suitable locus in studying the separation of M. nemestrina at population level. These findings are crucial in aiding the conservation management and translocation process of M. fascicularis populations in Malaysia.

  5. Inhalational Monkeypox Virus Infection in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roy eBarnewall

    2012-09-01

    Full Text Available An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV, and a nonhuman primate (NHP inhalation monkeypox model was developed in cynomologus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD was for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 µm, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 x 104 to 9.28 x 105 plaque forming units (pfu inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD50 was determined to be approximately 7.8 x 104 pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data.

  6. A pair choice test to identify female mating patterns in relation to ovulation in long-tailed macaques (Macaca fascicularis)

    NARCIS (Netherlands)

    Nikitopoulos, E.; Heistermann, M.; Vries, Han de; Hooff, J.A.R.A.M. van; Sterck, E.H.M.

    2006-01-01

    Female mammals may exert choice for mates directly by mating selectively. Alternatively, females can mate promiscuously, allowing sperm competition and/or cryptic female choice to operate. Primate sexual behaviour is probably a compromise between conflicting male and female interests, so it may be i

  7. Variation in hair δ13C and δ15N values in long-tailed macaques (Macaca fascicularis) from Singapore

    Science.gov (United States)

    Schillaci, Michael A.; Castellini, J. Margaret; Stricker, Craig A.; Jones-Engel, Lisa; Lee, Benjamin P.Y.-H.

    2014-01-01

    Much of the primatology literature on stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) has focused on African and New World species, with comparatively little research published on Asian primates. Here we present hair δ13C and δ15N isotope values for a sample of 33 long-tailed macaques from Singapore. We evaluate the suggestion by a previous researcher that forest degradation and biodiversity loss in Singapore have led to a decline in macaque trophic level. The results of our analysis indicated significant spatial variability in δ13C but not δ15N. The range of variation in δ13C was consistent with a diet based on C3 resources, with one group exhibiting low values consistent with a closed canopy environment. Relative to other macaque species from Europe and Asia, the macaques from Singapore exhibited a low mean δ13C value but mid-range mean δ15N value. Previous research suggesting a decline in macaque trophic level is not supported by the results of our study.

  8. Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis.

    Directory of Open Access Journals (Sweden)

    Sébastien Ballesta

    Full Text Available 3,4-methylenedioxy-N-methyl amphetamine (MDMA is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play. In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates' social behaviors.

  9. Mandibular reconstruction with a bioactive-coated cementless Ti6Al4V modular endoprosthesis in Macaca fascicularis

    NARCIS (Netherlands)

    Chanchareonsook, N.; Tideman, H.; Lee, S.; Hollister, S.J.; Flanagan, C.; Jansen, J.A.

    2014-01-01

    The titanium mandibular modular endoprosthesis fixed with polymethylmethacrylate cement in the medullary space of the mandible has been introduced in previous studies. However, the internal parts of these devices have been found to be prone to loosening and wound dehiscence. The current study introd

  10. Taxonomy Icon Data: crab-eating macaque [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available _NS.png http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Macaca+fascicularis&t=L http://biosciencedbc.jp/taxonomy..._icon/icon.cgi?i=Macaca+fascicularis&t=NL http://biosciencedbc.jp/taxonomy_i...con/icon.cgi?i=Macaca+fascicularis&t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Macaca+fascicularis&t=NS ...

  11. Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide

    Science.gov (United States)

    The present study was performed to determine experimental conditions for thalidomide induction of fetal malformations and to understand the molecular mechanisms underlying thalidomide teratogenicity in cynomolgus monkeys. Cynomolgus monkeys were orally administered (±)-thalidomid...

  12. Pediculosis in Macaca sylvanus of Gibraltar.

    Science.gov (United States)

    Cohn, Douglas L; Smith, Vincent; Pizarro, Mark; Jones-Engel, Lisa; Engel, Gregory; Fuentes, Agustin; Shaw, Eric; Cortes, John

    2007-04-10

    Pedicinus spp. parasitize several species of nonhuman primates. This is the first published report confirming the presence of Pedicinus albidus (Rudow) infestation in the free-ranging macaques (Macaca sylvanus) of Gibraltar. The diagnosis of pediculosis was based upon finding adult lice on host animals.

  13. Prototype Abstraction by Monkeys ("Macaca Mulatta")

    Science.gov (United States)

    Smith, J. David; Redford, Joshua S.; Haas, Sarah M.

    2008-01-01

    The authors analyze the shape categorization of rhesus monkeys ("Macaca mulatta") and the role of prototype- and exemplar-based comparison processes in monkeys' category learning. Prototype and exemplar theories make contrasting predictions regarding performance on the Posner-Homa dot-distortion categorization task. Prototype theory--which…

  14. Pathogenesis of lassa fever in cynomolgus macaques

    Directory of Open Access Journals (Sweden)

    Fritz Elizabeth A

    2011-05-01

    Full Text Available Abstract Background Lassa virus (LASV infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates. Methods Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease. Results Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17. Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers. Conclusion The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

  15. Cycloartane triterpenes from marine green alga Cladophora fascicularis

    Institute of Scientific and Technical Information of China (English)

    HUANG Xinping; ZHU Xiaobin; DENG Liping; DENG Zhiwei; LIN Wenhan

    2006-01-01

    Six cycloartanes were isolated from ethanol extract of marine green alga Cladophora fascicularis by column chromatography. Procedure of isolation and description of these compounds are given in this paper. The structures were elucidated as (1). 24-hydroperoxycycloart-25- en-3β-ol; (2).cycloart-25-en-3β 24-diol; (3). 25-hydroperoxycycloart-23-en-3β-ol; (4). cycloart-23-en-3β, 25-diol; (5).cycloart-23, 25-dien-3β-ol; and (6). cycloart-24-en-3β-ol by spectroscopic (MS, 1D and 2D NMR) data analysis. Cycloartane derivatives are widely distributed in terrestrial plants, but only few were obtained in the alga. All these compounds that have been isolated from terrestrial plants, were found in the marine alga for the first time.

  16. Cycloartane triterpenes from marine green alga Cladophora fascicularis

    Science.gov (United States)

    Huang, Xinping; Zhu, Xiaobin; Deng, Liping; Deng, Zhiwei; Lin, Wenhan

    2006-12-01

    Six cycloartanes were isolated from ethanol extract of marine green alga Cladophora fascicularis by column chromatography. Procedure of isolation and description of these compounds are given in this paper. The structures were elucidated as (1). 24-hydroperoxycycloart-25- en-3β-ol; (2). cycloart-25-en-3β 24-diol; (3). 25-hydroperoxycycloart-23-en-3β-ol; (4). cycloart-23-en-3β, 25-diol; (5). cycloart-23, 25-dien-3β-ol; and (6). cycloart-24-en-3β-ol by spectroscopic (MS, ID and 2D NMR) data analysis. Cycloartane derivatives are widely distributed in terrestrial plants, but only few were obtained in the alga. All these compounds that have been isolated from terrestrial plants, were found in the marine alga for the first time.

  17. Effect of physical restraint on glucose tolerance in cynomolgus monkeys.

    Science.gov (United States)

    Shirasaki, Yasufumi; Yoshioka, Naoya; Kanazawa, Kanpei; Maekawa, Tsuyoshi; Horikawa, Tadahiro; Hayashi, Toshiaki

    2013-06-01

    Physiologic stress has been demonstrated to impair glucose tolerance. Glucose tolerance tests were performed using six cynomolgus monkeys. Chair-restrained subjects elicited higher elevations of plasma glucose and cortisol compared with squeezing device-restrained subjects. The responses to a glucose challenge are altered by different restraint procedures.

  18. Determination of prey capture rates in the stony coral Galaxea fascicularis: a critical reconsideration of the clearance rate concept

    NARCIS (Netherlands)

    Osinga, R.; Delft, van S.; Lewaru, M.W.; Janse, M.; Verreth, J.A.J.

    2012-01-01

    In order to determine optimal feeding regimes for captive corals, prey capture by the scleractinian coral Galaxea fascicularis was determined by measuring clearance of prey items from the surrounding water. Colonies of G. fascicularis (sized between 200 and 400 polyps) were incubated in 1300 ml incu

  19. Characteristics of histologically confirmed endometriosis in cynomolgus monkeys

    Science.gov (United States)

    Nishimoto-Kakiuchi, A.; Netsu, S.; Matsuo, S.; Hayashi, S.; Ito, T.; Okabayashi, S.; Yasmin, L.; Yuzawa, K.; Kondoh, O.; Kato, A.; Suzuki, M.; Konno, R.; Sankai, T.

    2016-01-01

    STUDY QUESTION What are the characteristics of spontaneous endometriosis in cynomolgus monkeys? SUMMARY ANSWER Spontaneous endometriosis in cynomolgus monkeys exhibited similar characteristics to the human disease. WHAT IS KNOWN ALREADY One previous report described the prevalence and the basic histopathology of spontaneous endometriosis in cynomolgus monkeys. STUDY DESIGN, SIZE, DURATION Endometriotic lesions that had been histologically confirmed in 8 female cynomolgus monkeys between 5 and 21 years old were subjected to study. PARTICIPANTS/MATERIALS, SETTING, METHODS The monkeys died of, or were sacrificed because of, sickness consequent on endometriosis. Specimens were evaluated histopathologically with haematoxylin and eosin staining, iron staining and immunohistochemistry (CD10, CD31, α-SMA and PGP9.5), and by observing them under a microscope. MAIN RESULTS AND THE ROLE OF CHANCE Endometriotic and stromal cells (CD10-positive) with haemorrhage and inflammation were observed. Smooth muscle metaplasia and nerve fibres were also noted in the endometriotic lesions. Endometriotic lesions in lymph nodes were incidentally found. LIMITATIONS AND REASONS FOR CAUTION Since laparoscopic analysis for monitoring the disease state was not set as a parameter of the current study, time course changes (progression) of the disease were not assessed. WIDER IMPLICATIONS OF THE FINDINGS Further investigation of spontaneous endometriosis in cynomolgus monkeys may contribute to better understanding of the disease pathobiology. STUDY FUNDING/COMPETING INTEREST(S) No external funds were used for this study. A.N.K., S.M., S.H., T.I., O.K., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received lecture fees from Chugai Pharmaceutical Co., Ltd., unrelated to the submitted work. S.N., S. O., L.Y., K.Y. and T.S. have nothing to declare. TRIAL REGISTRATION NUMBER N/A. PMID:27591226

  20. Turritopsis fascicularis Fraser, 1943 (Cnidaria: Hydrozoa): redescription and discussion of its phylogenetic position within the genus.

    Science.gov (United States)

    Miglietta, Maria Pia

    2016-03-31

    Turritopsis fascicularis Fraser, 1943 was first described off Alligator Reef, Florida, USA, at a depth of 216 m. Presumably a deep-sea species, its validity has often been questioned due to the scarcity of available records. In this paper, T. fascicularis is re-described from some mature colonies from the upper slope of the Gulf of Mexico. Furthermore, new pictures of the colony, polyps, and medusa buds, are provided. A ~600bp sequence of the large ribosomal subunit of the mitochondrial RNA (lsu-rRNA, 16S), also known as the Hydrozoan barcoding molecule, is used for the first time to confirm the validity of T. fascicularis as a species, and analyze its phylogenetic position within the genus Turritopsis.

  1. Beneficial Insect Attraction to Milkweeds (Asclepias speciosa, Asclepias fascicularis) in Washington State, USA.

    Science.gov (United States)

    James, David G; Seymour, Lorraine; Lauby, Gerry; Buckley, Katie

    2016-06-29

    Native plant and beneficial insect associations are relatively unstudied yet are important in native habitat restoration programs for improving and sustaining conservation biological control of arthropod pests in agricultural crops. Milkweeds (Asclepias spp.) are currently the focus of restoration programs in the USA aimed at reversing a decline in populations of the milkweed-dependent monarch butterfly (Danaus plexippus); however, little is known of the benefits of these plants to other beneficial insects. Beneficial insects (predators, parasitoids, pollinators) attracted to two milkweed species (Asclepias speciosa, Asclepias fascicularis) in central Washington State, WA, USA were identified and counted on transparent sticky traps attached to blooms over five seasons. Combining all categories of beneficial insects, means of 128 and 126 insects per trap were recorded for A. speciosa and A. fascicularis, respectively. Predatory and parasitic flies dominated trap catches for A. speciosa while parasitic wasps were the most commonly trapped beneficial insects on A. fascicularis. Bees were trapped commonly on both species, especially A. speciosa with native bees trapped in significantly greater numbers than honey bees. Beneficial insect attraction to A. speciosa and A. fascicularis was substantial. Therefore, these plants are ideal candidates for habitat restoration, intended to enhance conservation biological control, and for pollinator conservation. In central Washington, milkweed restoration programs for enhancement of D. plexippus populations should also provide benefits for pest suppression and pollinator conservation.

  2. Beneficial Insect Attraction to Milkweeds (Asclepias speciosa, Asclepias fascicularis in Washington State, USA

    Directory of Open Access Journals (Sweden)

    David G. James

    2016-06-01

    Full Text Available Native plant and beneficial insect associations are relatively unstudied yet are important in native habitat restoration programs for improving and sustaining conservation biological control of arthropod pests in agricultural crops. Milkweeds (Asclepias spp. are currently the focus of restoration programs in the USA aimed at reversing a decline in populations of the milkweed-dependent monarch butterfly (Danaus plexippus; however, little is known of the benefits of these plants to other beneficial insects. Beneficial insects (predators, parasitoids, pollinators attracted to two milkweed species (Asclepias speciosa, Asclepias fascicularis in central Washington State, WA, USA were identified and counted on transparent sticky traps attached to blooms over five seasons. Combining all categories of beneficial insects, means of 128 and 126 insects per trap were recorded for A. speciosa and A. fascicularis, respectively. Predatory and parasitic flies dominated trap catches for A. speciosa while parasitic wasps were the most commonly trapped beneficial insects on A. fascicularis. Bees were trapped commonly on both species, especially A. speciosa with native bees trapped in significantly greater numbers than honey bees. Beneficial insect attraction to A. speciosa and A. fascicularis was substantial. Therefore, these plants are ideal candidates for habitat restoration, intended to enhance conservation biological control, and for pollinator conservation. In central Washington, milkweed restoration programs for enhancement of D. plexippus populations should also provide benefits for pest suppression and pollinator conservation.

  3. Hepatitis G virus genomic RNA is pathogenic to Macaca mulatta

    Institute of Scientific and Technical Information of China (English)

    Hao Ren; Fen-Lu Zhu; Ming-Mei Cao; Xin-Yu Wen; Ping Zhao; Zhong-Tian Qi

    2005-01-01

    AIM: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum.METHODS: Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological,histological assays.RESULTS: Serum HGV RNA was detectable in all the 3Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohistochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes.RT-PCR and quantitative PCR results showed that HGV could replicate in liver.CONCLUSION: The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.

  4. Can Monkeys (Macaca mulatta) Represent Invisible Displacement?

    Science.gov (United States)

    Filion, Christine M.; Washburn, David A.; Gulledge, Jonathan P.

    1996-01-01

    Four experiments were conducted to assess whether or not rhesus macaques (Macaca mulatta) could represent the unperceived movements of a stimulus. Subjects were tested on 2 computerized tasks, HOLE (monkeys) and LASER (humans and monkeys), in which subjects needed to chase or shoot at, respectively, a moving target that either remained visible or became invisible for a portion of its path of movement. Response patterns were analyzed and compared between target-visible and target-invisible conditions. Results of Experiments 1, 2, and 3 demonstrated that the monkeys are capable of extrapolating movement. That this extrapolation involved internal representation of the target's invisible movement was suggested but not confirmed. Experiment 4, however, demonstrated that the monkeys are capable of representing the invisible displacements of a stimulus.

  5. Adaptations in Basal and Hypothalamic–Pituitary–Adrenal-Activated Deoxycorticosterone Responses Following Ethanol Self-administration in Cynomolgus Monkeys

    Science.gov (United States)

    Jimenez, Vanessa A.; Porcu, Patrizia; Morrow, A. Leslie; Grant, Kathleen A.

    2017-01-01

    Acute ethanol activates the hypothalamic–pituitary–adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys. The present study investigated HPA axis regulation of circulating DOC concentration over the course of ethanol (4% w/v) induction and self-administration in non-human primates (Macaca fasciculata, n = 10). Plasma DOC, measured by radioimmunoassay, was compared at baseline (ethanol naïve), during schedule-induced polydipsia, and following 6-months of 22 h/day access to ethanol and water. The schedule induction of ethanol drinking did not alter basal DOC levels but selectively dampened the DOC response to pharmacological challenges aimed at the anterior pituitary (ovine corticotrophin-releasing hormone) and adrenal gland (post-dexamethasone adrenocorticotropin hormone), while pharmacological inhibition of central opioid receptors with naloxone greatly enhanced the DOC response during induction. Following 6 months of ethanol self-administration, basal DOC levels were increased more than twofold, while responses to each of the challenges normalized somewhat but remained significantly different than baseline. These data show that HPA axis modulation of the neuroactive steroid precursor DOC is markedly altered by the schedule induction of ethanol drinking and long-term voluntary ethanol self-administration. The consequences of chronic ethanol consumption on HPA axis regulation of DOC point toward allostatic modification of hypothalamic and adrenal function. PMID:28220108

  6. Biosorption and desorption of Cd2+ from wastewater by dehydrated shreds of Cladophora fascicularis

    Institute of Scientific and Technical Information of China (English)

    DENG Liping; ZHU Xiaobin; SU Yingying; SU Hua; WANG Xinting

    2008-01-01

    The adsorption and desorption of algae Cladophora fascicularis and their relation with initial Cd2+ concentration,initial pH,and co-existing ions were studied.Adsorption equilibrium and biosorption kinetics were established from batch experiments.The adsorption equilibrium was adequately described by the Langmuir isotherm,and biosorption kinetics was in pseudo-second order model.The experiment on co-existing ions showed that the biosorption capacity of biomass decreased with an increasing concentration of competing ions.Desorption experiments indicated that EDTA was efficient desorbent for recovery from Cd2+.With high capacities of metal biosorption and desorption,the biomass of Cladophora fascicularis is promising as a cost-effective biosorbent for the removal of Cd2+ from wastewater.

  7. Epizoic acoelomorph flatworms impair zooplankton feeding by the scleractinian coral Galaxea fascicularis

    OpenAIRE

    Wijgerde, T.H.M.; Schots, P.; Onselen, van, E.; Karruppannan, E.W.; Verreth, J.A.J.; Osinga, R.

    2013-01-01

    Many scleractinian coral species host epizoic acoelomorph flatworms, both in aquaculture and in situ. These symbiotic flatworms may impair coral growth and health through light-shading, mucus removal and disruption of heterotrophic feeding. To quantify the effect of epizoic flatworms on zooplankton feeding, we conducted video analyses of single polyps of Galaxea fascicularis (Linnaeus 1767) grazing on Artemia nauplii in the presence and absence of symbiotic flatworms. 18S DNA analysis reveale...

  8. Epizoic acoelomorph flatworms impair zooplankton feeding by the scleractinian coral Galaxea fascicularis

    OpenAIRE

    Tim Wijgerde; Pauke Schots; Eline Van Onselen; Max Janse; Eric Karruppannan; Verreth, Johan A. J.; Ronald Osinga

    2012-01-01

    Summary Many scleractinian coral species host epizoic acoelomorph flatworms, both in aquaculture and in situ. These symbiotic flatworms may impair coral growth and health through light-shading, mucus removal and disruption of heterotrophic feeding. To quantify the effect of epizoic flatworms on zooplankton feeding, we conducted video analyses of single polyps of Galaxea fascicularis (Linnaeus 1767) grazing on Artemia nauplii in the presence and absence of symbiotic flatworms. 18S DNA analysis...

  9. Phytochemical and pharmacological evaluation of prop roots of Pandanus fascicularis Lam

    Institute of Scientific and Technical Information of China (English)

    Jothimani Rajeswari; Karthikeyan Kesavan; Balasundaram Jayakar

    2011-01-01

    Objective:To evaluate the anti-inflammatory and analgesic activities of the ethanol and aqueous extracts of prop roots of Pandanus fascicularis (P. fascicularis) Lam (pandanaceae). And provide experimental evidence for its traditional use such as rheumatoid arthritis and spasmodic. Methods:The anti-inflammatory activity was observed by carrageenan-induced edema of the hind paw of rats. Analgesic activities of prop roots ofP. fascicularis were determined using acetic acid induced writhing model and tail clip method in mice and rat, respectively. The ethanol fraction was then subjected to chromatographic analysis and a compound has been isolated and characterized byIR,1H-NMR and mass spectroscopy.Results: Edema suppressant effect of ethanol extract was found to be37.03% inhibition whereas aqueous extract was found to be 63.22% inhibition after 3 h which was nearly equivalent to that of 10mg/kg of indomethacin (67.81%). Percentage inhibition of writhing compared to control were63.15%, 54.38%, 14.90%for aspirin, aqueous extract and ethanolic extract, respectively. Both ethanol and aqueous extracts show significant activity against appropriate controls after60 min of treatment on tail clip method. The structure of the isolated compound is may be characterized as Hepta deca-5-ene-1-ol by analysis it’sIR,1H-NMR and mass spectroscopy data.Conclusions: The extracts of prop roots ofP. fascicularis produce significant analgesic and anti-inflammatory activities, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.

  10. ANTIDIURETIC ACTIVITY OF AQUEOUS AND ETHANOLIC EXTRACTS OF PROP ROOTS OF PANDANUS FASCICULARIS LAM.

    Directory of Open Access Journals (Sweden)

    Jothimani Rajeswari et al.

    2012-04-01

    Full Text Available The extracts of the prop roots of Pandanus fascicularis Lam (Family: Pandanaceae is claimed as an antidiuretic by some traditional practitioners. However, the validity of this claim has not been scientifically proven or refuted. The aim of this study was to evaluate the antidiuretic potential of ethanol and aqueous extracts of prop roots of P. fascicularis in rats following oral administration. Ethanol and aqueous extracts were prepared from P. facicularis by percolation and cold maturation, respectively. Furosemide was used as a diuretic agent to induce diuresis. Vasopressin (ADH was used as a standard. The results demonstrated both the ethanol and aqueous extracts of P. facicularis and ADH significantly impaired the total urine output. However, antidiuretic potential of ethanolic extract was similar to that of ADH. The extracts caused a significant decrease in natriuresis and kaliuresis. From this study, we can conclude that ethanol extract of prop roots of Pandanus fascicularis has beneficial effects on anti diuretic activity. It has the potential to impart therapeutic effect in diuretic.

  11. Evaluation of the cynomolgus monkey stomach: recommendations for standard sampling procedures in nonclinical safety studies.

    Science.gov (United States)

    Vidal, Justin D; Mirabile, Rosanna C; Thomas, Heath C

    2008-02-01

    The cynomolgus macaque is the most commonly used nonhuman primate in nonclinical toxicity testing, but the macroscopic and microscopic anatomy of the stomach in the cynomolgus macaque is poorly described. To develop a reliable sampling method for histologic evaluation of the cynomolgus macaque stomach in regulatory toxicity studies, the stomachs of control animals were prospectively evaluated using an extensive sectioning pattern. The stomach of the cynomolgus macaque differs from that described for the human stomach and has a prominent fundus that lacks parietal cells. A description of the macroscopic and microscopic anatomy is presented along with a recommended sectioning pattern for nonclinical toxicity studies and discussion of species differences. A thorough understanding of normal anatomy and species comparisons are critical to interpretation of potential toxicity findings and assessment of risk in humans.

  12. Depression and altered serum lipids in cynomolgus monkeys consuming a Western diet

    OpenAIRE

    Chilton, Floyd H; Lee, Tammy C.; Willard, Stephanie L.; Ivester, Priscilla; Sergeant, Susan; Register, Thomas C.; Shively, Carol A.

    2011-01-01

    Depression and altered serum lipids in cynomolgus monkeys on a Western diet. Research over the past 15 years has suggested a high comorbidity of depression and coronary heart disease (CHD). However the mechanisms responsible for this relationship are poorly understood. This study was designed to examine the relationships between depressive behaviors and concentrations of circulating lipids and lipid signaling molecules that may be common to both CHD and depression in a cohort of cynomolgus mo...

  13. Methotrexate for immunosuppression in life-supporting pig-to-cynomolgus monkey renal xenotransplantation.

    Science.gov (United States)

    Cozzi, Emanuele; Cadrobbi, Roberto; Baldan, Nicola; Dedja, Arben; Calabrese, Fiorella; Castagnaro, Massimo; Fante, Fabio; Boldrin, Massimo; Iacopetti, Ilaria; Ravarotto, Licia; Carraro, Paolo; Bronte, Vincenzo; De Santo, Carmela; Busetto, Roberto; Plebani, Mario; Cancellotti, Francesco Maria; Rigotti, Paolo; Thiene, Gaetano; Ancona, Ermanno

    2003-11-01

    Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent xenotransplantation models, but the data generated so far with MTX in pig-to-baboon cardiac transplantation studies have been disappointing. The potential of this agent was consequently explored in a life-supporting pig-to-primate renal model using the cynomolgus monkey as the recipient species. Introductory in vitro and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted in three cynomolgus monkeys. Subsequently, 10 cynomolgus monkey recipients of a life-supporting kidney from human decay-accelerating factor transgenic pigs were administered MTX intravenously according to three different regimens. All the animals also received cyclosporine A and steroids. In addition, mycophenolate sodium (MPS) was administered post-operatively in two of the three groups of transplanted animals. At clinically relevant concentrations, MTX is able in vitro to inhibit the mixed lymphocyte reactions (MLR) in cynomolgus monkeys. After intravenous administration, moreover, exposure of cynomolgus monkeys to MTX appeared to be higher than had been previously reported in baboons. Graft function was observed in the transplanted animals, which survived from 0 to 41 days. All but two animals revealed acute humoral rejection in the explanted graft and developed diarrhea. Diarrhea was the cause of euthanasia in five cases. It was unrelated to the administration of MPS and associated with severe histopathological signs of enteritis. This study demonstrates that the pharmacokinetic and pharmacodynamic profiles if MTX vary substantially between non-human primate species. In vitro, MTX has immunosuppressive properties in the cynomolgus monkey at clinically relevant concentrations. In vivo, MTX has a very narrow therapeutic window in cynomolgus monkeys, however, as it does in baboons. We conclude that MTX is scarcely effective as an immunosuppressant, be it for induction or maintenance, in pig-to-cynomolgus

  14. Pharmacokinetic studies on quinacrine following intrauterine administration to cynomolgus monkeys.

    Science.gov (United States)

    Dubin, N H; Blake, D A; DiBlasi, M C; Parmley, T H; King, T M

    1982-12-01

    Recent efforts have been made to develop a chemical oviductal occluding agent. Intrauterine quinacrine has been used in certain areas of the world with moderate success in effected tubal closure. This report presents the pharmacokinetics of a quinacrine solution (30 mg) as administered to cynomolgus monkeys via the intrauterine route, compared with intravascular injection. The data show rapid transfer of the drug from the uterine to the vascular compartment and uptake by almost all tissues examined. Although plasma concentrations disappear within 24 hours, levels can be detected in most tissues for at least 1 week following intrauterine injection. After 28 days, however, tissue levels of the drug are absent or near the limit of detection.

  15. The Distribution of MAP-2 Phosphorylation in Cerebral Cortex of Long-Tailed Monkey Fetuses (Macaca fascicularis in the Last Trimester of Gestation

    Directory of Open Access Journals (Sweden)

    Tri Wahyu Pangestiningsih

    2015-11-01

    Full Text Available Memories are storage in cholinoceptive cells, the cells which are enriched with microtubule-associated protein 2 (MAP-2 that localized in the neuronal dendrite and the cell bodies. Phosphorylation of MAP-2 may increase memory with reduce stability of dendrite by altered dendrite length and lead new side-branches of neuronal as a neuronal plasticity processes in cerebral cortex. The aim of this research is to study the distribution of MAP-2 phosphorylation neurons in cerebral cortex of long-tailed macaques in the third semester of gestationalimmunohistochemically using avidin biotin conjugated complex method. Neurons MAP-2 phosphorylation immunoreactive were located in dendrites and cell bodies, mostly in pyramidal neurons of cerebral cortex. Intensity of MAP-2 phosphorylation immunoreactivity in layer V were stronger than another layer and the neurons that very intensely stained were the pyramidal cells in frontal and parietal lobes, that was suggested that neurons in this areas more responsive to neuroplasticity. From the results we concluded that MAP-2 phosphorylation already distributed in the cerebral cortex of long-tailed macaque fetuses at the last trimester of gestation, mostly in the pyramidal cells of layer V that is suggested plays a role for preparation of memoryformation.Keywords: fetus, long-tailed monkey, cerebral cortex, memory, MAP-2 phosphorylation

  16. The use of a polycaprolactone-tricalcium phosphate scaffold for bone regeneration of tooth socket facial wall defects and simultaneous immediate dental implant placement in Macaca fascicularis.

    Science.gov (United States)

    Goh, Bee Tin; Chanchareonsook, Nattharee; Tideman, Henk; Teoh, Swee Hin; Chow, James Kwok Fai; Jansen, John A

    2014-05-01

    Bone regeneration and aesthetic outcomes may be compromised when immediate implants are placed at extraction sites with dehiscence defects. The aim of this study was to compare, in a monkey model, peri-implant bone regeneration and implant stability after immediate implant placement into tooth sockets with facial wall defects in two treatment groups. In eight control monkeys, the bony defect was reconstructed with autogenous particulate bone, whereas in 10 test monkeys a polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold was used. The monkeys were sacrificed after 6 months and the specimens were analyzed by histology and histomorphometry. Better maintenance of facial bone contour was noted in the test group; however, bone regeneration was seen only at areas adjacent to a bony wall of the defect. The mean bone-to-implant contact was 27.6 ± 19.1% (control group) versus 6.8 ± 7.9% (test group). The mean bone area percentage was 11.8 ± 10.1% (control group) versus 6.8 ± 6.9% (test group). Implant survival was 100% at 6 months for both the groups. It was concluded that although the use of a PCL-TCP scaffold showed better maintenance of the alveolar contour as compared to autogenous particulate bone at 6 months, there was minimal bone regeneration within the defect.

  17. The use of a polycaprolactone-tricalcium phosphate scaffold for bone regeneration of tooth socket facial wall defects and simultaneous immediate dental implant placement in Macaca fascicularis

    NARCIS (Netherlands)

    Goh, B.T.; Chanchareonsook, N.; Tideman, H.; Teoh, S.H.; Chow, J.K.; Jansen, J.A.

    2014-01-01

    Bone regeneration and aesthetic outcomes may be compromised when immediate implants are placed at extraction sites with dehiscence defects. The aim of this study was to compare, in a monkey model, peri-implant bone regeneration and implant stability after immediate implant placement into tooth socke

  18. Effect of Elevated Carbon Dioxide on Two Scleractinian Corals: Porites cylindrica (Dana, 1846 and Galaxea fascicularis (Linnaeus, 1767

    Directory of Open Access Journals (Sweden)

    Yii-Siang Hii

    2009-01-01

    Full Text Available This study reveals the effect of elevated pCO2 on Porites cylindrica and Galaxea fascicularis. The corals responded differently under elevated pCO2. Zooxanthellae cell density, cell mitotic index, and photosynthesis rate of P. cylindrica decreased drastically under the elevated pCO2. At the end of the experiment, P. cylindrica suffered from a declining calcium carbonate precipitation rate. G. fascicularis increased its respiration rate and expelled 71% of its symbiotic zooxanthellae algae under elevated pCO2. Photosynthetic pigments in the remaining zooxanthellae algae increased from 1.85 to 11.5 times to sustain its photosynthetic outputs. At the end of the experiment, G. fascicularis managed to increase the rate of its calcium carbonate precipitation. Increase pCO2 in the atmosphere may affect species diversity of coral reefs.

  19. Craniodental variation among Macaques (Macaca, nonhuman primates

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    Pan Ruliang

    2002-05-01

    Full Text Available Abstract Background In terms of structure and function, the skull is one of the most complicated organs in the body. It is also one of the most important parts in terms of developmental and evolutionary origins. This complexity makes it difficult to obtain evolutionary assessments if, as is usually the case with fossils, only part of the skull is available. For this reason this study involves a set of comparisons whereby the smallest functional units are studied first, and these built up, through a triple-nested hierarchical design, into more complex anatomical regions and eventually into the skull-as-a-whole. This design has been applied to macaques (Macaca in order to reveal patterns of variation at the different levels. The profiles of such variation have been obtained both within and between species. This has lead to a search for the skull parts that have undergone similar selection pressures during evolution and comparable development patterns in both ontogeny and phylogeny. Results Morphometric analysis (Principal Components was used to obtain these profiles of species and sex separations based on 77 cranial variables from 11 species of macaques. The results showed that 7 functional units could be aggregated into three functionally reasonable anatomical regions on the basis of similarities in profiles. These were: the masticatory apparatus containing mandible, lower teeth and upper teeth, the face as a whole combining maxilla (actually lower face and upper face, and the cranium as a whole involving cranium and calvaria. Twenty-six variables were finally selected for analyzing the morphology of the whole skull. This last showed an overall profile similar to that revealed in the masticatory apparatus but also contained additional information pertaining to individual species and species-groups separations. Conclusions The study provides a model for carrying out analysis of species separations and sex variation simultaneously. Through this

  20. Novel Polymorphic Microsatellite Markers Reveal Genetic Differentiation between Two Sympatric Types of Galaxea fascicularis.

    Directory of Open Access Journals (Sweden)

    Yuichi Nakajima

    Full Text Available The reef-building, scleractinian coral, Galaxea fascicularis, is classified into soft and hard types, based on nematocyst morphology. This character is correlated with the length of the mitochondrial non-coding region (mt-Long: soft colony type, and nematocysts with wide capsules and long shafts; mt-Short: hard colony type, and nematocysts with thin capsules and short shafts. We isolated and characterized novel polymorphic microsatellite markers for G. fascicularis using next-generation sequencing. Based upon the mitochondrial non-coding region, 53 of the 97 colonies collected were mt-Long (mt-L and 44 were mt-Short (mt-S. Among the 53 mt-L colonies, 27 loci were identified as amplifiable, polymorphic microsatellite loci, devoid of somatic mutations and free of scoring errors. Eleven of those 27 loci were also amplifiable and polymorphic in the 44 mt-S colonies; these 11 are cross-type microsatellite loci. The other 16 loci were considered useful only for mt-L colonies. These 27 loci identified 10 multilocus lineages (MLLs among the 53 mt-L colonies (NMLL/N = 0.189, and the 11 cross-type loci identified 7 MLLs in 44 mt-S colonies (NMLL/N = 0.159. Significant genetic differentiation between the two types was detected based on the genetic differentiation index (FST = 0.080, P = 0.001. Bayesian clustering also indicated that these two types are genetically isolated. While nuclear microsatellite genotypes also showed genetic differentiation between mitochondrial types, the mechanism of divergence is not yet clear. These markers will be useful to estimate genetic diversity, differentiation, and connectivity among populations, and to understand evolutionary processes, including divergence of types in G. fascicularis.

  1. UniProt search blastx result: AK289220 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK289220 J100065H20 Q60HG6|CATC_MACFA Dipeptidyl-peptidase 1 precursor (EC 3.4.14.1) (Dipeptidyl-pep...tidase I) (DPP-I) (DPPI) (Cathepsin C) (Cathepsin J) (Dipeptidyl transferase) [Contains: Dipeptidyl-pep...tidase 1 exclusion domain chain (Dipeptidyl-peptidase I exclusion domain chain); Dipeptidyl-pept...idase 1 heavy chain (Dipeptidyl-peptidase I heavy chain); Dipeptidyl-peptidase 1 light chain (Dipep...tidyl-peptidase I light chain)] - Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey) 6.00E-22 ...

  2. Histologic fate of dermal grafts following implantation for temporomandibular joint meniscal perforation: a preliminary study.

    Science.gov (United States)

    Stewart, H M; Hann, J R; DeTomasi, D C; Neville, B W; DeChamplain, R W

    1986-11-01

    A study was carried out to evaluate the histologic changes of meniscus perforation repair associated with dermal grafts to the temporomandibular joint of cynomolgus monkeys (Macaca fascicularis) following surgical perforation of the meniscus. Dermal grafts were studied histologically at 3-week, 6-week, 3-month, and 6-month intervals. Results showed early attachment of the dermal graft to the meniscus, followed by gradual incorporation of the graft into the meniscus and subsequent return of the meniscal-graft complex to a normal meniscal architecture.

  3. Rhesus monkeys (Macaca mulatta) map number onto space

    OpenAIRE

    Drucker, Caroline B.; Brannon, Elizabeth M.

    2014-01-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance...

  4. Evaluation of serum lipid, thyroid, and hepatic clinical chemistries in association with serum perfluorooctanesulfonate (PFOS) in cynomolgus monkeys after oral dosing with potassium PFOS.

    Science.gov (United States)

    Chang, Shu-Ching; Allen, Bruce C; Andres, Kara L; Ehresman, David J; Falvo, Ria; Provencher, Anne; Olsen, Geary W; Butenhoff, John L

    2017-01-23

    An oral dose study with PFOS was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fasicularis). While control group (n=6/sex) was sham-dosed with vehicle (0.5% Tween® 20 and 5% ethanol in DI water) during the study, low-dose group (n=6/sex) received one single K(+)PFOS dose (9 mg/kg) and high-dose group (n=6/sex) received three separate K(+)PFOS doses (11 - 17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior, during, and after PFOS administration for up to one year and they were analyzed for PFOS concentration and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 µg/mL. Compared to time-matched controls, administration of K(+)PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the HDL fraction), although not toxicologically significant, was observed and the corresponding lower-bound 5(th) percentile benchmark concentrations (BMCL1sd) were 74 and 76 µg/mL for male and female monkeys, respectively. This compares to the 2011-2012 geometric mean serum PFOS level of 6.3 ng/mL (0.00063 µg/mL) in US general population would result in 4 orders of magnitude for margin of exposure.

  5. Thymic immunopathology and progression of SIVsm infection in cynomolgus monkeys.

    Science.gov (United States)

    Li, S L; Kaaya, E E; Ordónez, C; Ekman, M; Feichtinger, H; Putkonen, P; Böttiger, D; Biberfeld, G; Biberfeld, P

    1995-05-01

    Thymuses from 22 cynomolgus monkeys infected with simian immunodeficiency virus (SIVsm) developed characteristic cortical and medullary changes including formation of B-cell follicles (8/21) and accumulation of virus immune complexes. Advanced thymic histopathology was correlated with more pronounced immunodeficiency. SIVsm provirus was detected by polymerase chain reaction (PCR) in most (16/18) thymuses and spliced viral env mRNA in 3 (3/7) thymuses with advanced histopathologic changes indicative of thymic SIVsm replication. By combined in situ hybridization (ISH) and immunohistochemistry, viral RNA was localized mainly to the follicular dendritic network, macrophages, multinucleated giant cells, and lymphocytes of the medullary regions. Latent infection by an Epstein-Barr-related herpesvirus (HVMF1) was also found by PCR and by ISH in medullary regions of three (3 of 8) thymuses with B-cell follicles, suggestive of an inductive role for B-cell proliferation in these thymuses. In a control group of HIV-2-infected nonimmunosuppressed monkeys, no comparable thymic changes were observed. Our results indicate that SIV, and probably by analogy HIV, can have direct and diverse pathogenic effects on the thymus that are important in the development of simian (human) AIDS.

  6. Zika viral dynamics and shedding in rhesus and cynomolgus macaques

    Science.gov (United States)

    Osuna, Christa E; Lim, So-Yon; Deleage, Claire; Griffin, Bryan D; Stein, Derek; Schroeder, Lukas T; Omange, Robert Were; Best, Katharine; Luo, Ma; Hraber, Peter T; Andersen-Elyard, Hanne; Ojeda, Erwing Fabian Cardozo; Huang, Scott; Vanlandingham, Dana L; Higgs, Stephen; Perelson, Alan S; Estes, Jacob D; Safronetz, David; Lewis, Mark G; Whitney, James B

    2017-01-01

    Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection was cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans. PMID:27694931

  7. Development of a Zika Virus Infection Model in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Fusataka Koide

    2016-12-01

    Full Text Available Limited availability of Indian rhesus macaques (IRM is a bottleneck to study Zika virus (ZIKV pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM model for ZIKV infection. In brief, six MCMs (seronegative for dengue and ZIKV were subdivided into 3 cohorts with a male and female each and challenged with different doses of Asian PRVABC59 (Puerto Rico or FSS13025 (Cambodia or African (IBH30656 lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva and urine and tissues (testes and brain were assessed for viral load by quantitative RT-PCR and neutralizing antibodies (Nab by 50% Plaque Reduction Neutralization Test (PRNT50 at various times post infection (p.i. PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2 to 3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 ×103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.

  8. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    Science.gov (United States)

    Bimber, Benjamin N.; Reed, Jason S.; Uebelhoer, Luke S.; Bhusari, Amruta; Hammond, Katherine B.; Klug, Alex; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus; Sacha, Jonah B.

    2016-01-01

    Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics. PMID:27829026

  9. Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

    NARCIS (Netherlands)

    de Boer, E.; Samuel, S.; French, D. N.; Warram, J. M.; Schoeb, T. R.; Rosenthal, E. L.; Zinn, K. R.

    2016-01-01

    Purpose: The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques. Procedures: Total IR700 and intact cetuximab-IR700

  10. Immunohistochemical identification of kidney nephron segments in the dog, rat, mouse, and cynomolgus monkey.

    Science.gov (United States)

    Bauchet, Anne-Laure; Masson, Regis; Guffroy, Magali; Slaoui, Mohamed

    2011-12-01

    Kidney is a major target organ in preclinical studies. In recent years, intense research has been undertaken to characterize novel renal toxicity biomarkers. In this context, we studied nephron segment specific antibodies against aquaporin-1 (AQP-1), α-glutathione-S-transferase (alpha-GST), Tamm-Horsfall protein (TH), calbindin-D(28K) (CalD), and aquaporin-2 (AQP-2), using an immunoperoxidase method on formalin-fixed paraffin-embedded kidney tissues of dogs, rats, mice, and Cynomolgus monkeys. AQP-1 was specific for proximal tubules and thin descending limbs of Henle's loops and AQP-2 for connecting and collecting ducts in dogs, rats, mice, and Cynomolgus monkeys. Alpha-GST stained the straight part of proximal tubules in dogs and proximal convoluted tubule and straight part of proximal tubules in rats. TH was specific for thick ascending limbs of Henle's loops in mice, rats, dogs, and Cynomolgus monkeys and stained additionally scattered cells in cortical connecting/collecting ducts of dogs. CalD was found in distal convoluted tubules and cortical connecting and collecting ducts of dogs, rats, and mice and in distal convoluted tubules, connecting ducts, and cortical and medullary collecting ducts of Cynomolgus monkey. This panel of antibodies may be a helpful tool to identify renal tubules by light microscopy in preclinical studies and to validate new biomarkers of renal toxicity.

  11. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Zhenhua [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Department of Anatomy, Anhui Medical University, Hefei, 230032 (China); Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Chen, Zhiguo, E-mail: chenzhiguo@gmail.com [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Stanford Institute for Stem Cell Biology and Regenerative Medicine and Department of Neurosurgery, Stanford, CA (United States); Zhang, Y. Alex, E-mail: yaz@bjsap.org [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China)

    2011-12-10

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  12. Severe Encephalitis in Cynomolgus Macaques Exposed to Aerosolized Eastern Equine Encephalitis Virus

    Science.gov (United States)

    2007-08-01

    report here that cynomolgus macaques are also suitable as a model for aerosol exposure to EEE viruses. MATERIALS AND METHODS Animals. Healthy, adult... trocar , the arterial catheter was routed through the subcuta- neous space to the inguinal incision. With an 18-gauge needle, the arterial catheter was

  13. Epizoic acoelomorph flatworms impair zooplankton feeding by the scleractinian coral Galaxea fascicularis.

    Science.gov (United States)

    Wijgerde, Tim; Schots, Pauke; Van Onselen, Eline; Janse, Max; Karruppannan, Eric; Verreth, Johan A J; Osinga, Ronald

    2013-01-15

    Many scleractinian coral species host epizoic acoelomorph flatworms, both in aquaculture and in situ. These symbiotic flatworms may impair coral growth and health through light-shading, mucus removal and disruption of heterotrophic feeding. To quantify the effect of epizoic flatworms on zooplankton feeding, we conducted video analyses of single polyps of Galaxea fascicularis (Linnaeus 1767) grazing on Artemia nauplii in the presence and absence of symbiotic flatworms. 18S DNA analysis revealed that flatworms inhabiting G. fascicularis belonged to the genus Waminoa (Convolutidae), which were hosted at a density of 3.6±0.4 individuals polyp(-1). Polyps hosting flatworms exhibited prey capture rates of 2.2±2.5, 3.4±4.5 and 2.7±3.4 nauplii polyp(-1) 30 min(-1) at prey concentrations of 250, 500 and 1,000 nauplii L(-1), respectively. Polyps that had their flatworms removed displayed prey capture rates of 2.7±1.6, 4.8±4.1 and 16.9±10.3 nauplii polyp(-1) 30 min(-1). Significant main and interactive effects of flatworm presence and ambient prey concentration were found, reflected by the fact that flatworms significantly impaired host feeding rates at the highest prey density of 1,000 nauplii L(-1). In addition, flatworms displayed kleptoparasitism, removing between 0.1±0.3 and 0.6±1.1 nauplii 30 min(-1) from the oral disc of their host, or 5.3±3.3 to 50.0±2.1% of prey acquired by the coral. We suggest classifying the coral-associated Waminoa sp. as an epizoic parasite, as its presence may negatively affect growth and health of the host.

  14. Epizoic acoelomorph flatworms impair zooplankton feeding by the scleractinian coral Galaxea fascicularis

    Directory of Open Access Journals (Sweden)

    Tim Wijgerde

    2012-10-01

    Many scleractinian coral species host epizoic acoelomorph flatworms, both in aquaculture and in situ. These symbiotic flatworms may impair coral growth and health through light-shading, mucus removal and disruption of heterotrophic feeding. To quantify the effect of epizoic flatworms on zooplankton feeding, we conducted video analyses of single polyps of Galaxea fascicularis (Linnaeus 1767 grazing on Artemia nauplii in the presence and absence of symbiotic flatworms. 18S DNA analysis revealed that flatworms inhabiting G. fascicularis belonged to the genus Waminoa (Convolutidae, which were hosted at a density of 3.6±0.4 individuals polyp−1. Polyps hosting flatworms exhibited prey capture rates of 2.2±2.5, 3.4±4.5 and 2.7±3.4 nauplii polyp−1 30 min−1 at prey concentrations of 250, 500 and 1,000 nauplii L−1, respectively. Polyps that had their flatworms removed displayed prey capture rates of 2.7±1.6, 4.8±4.1 and 16.9±10.3 nauplii polyp−1 30 min−1. Significant main and interactive effects of flatworm presence and ambient prey concentration were found, reflected by the fact that flatworms significantly impaired host feeding rates at the highest prey density of 1,000 nauplii L−1. In addition, flatworms displayed kleptoparasitism, removing between 0.1±0.3 and 0.6±1.1 nauplii 30 min−1 from the oral disc of their host, or 5.3±3.3 to 50.0±2.1% of prey acquired by the coral. We suggest classifying the coral-associated Waminoa sp. as an epizoic parasite, as its presence may negatively affect growth and health of the host.

  15. Reference values of hematology, biochemistry, and blood type in cynomolgus monkeys from cambodia origin.

    Science.gov (United States)

    Choi, Kangmoo; Chang, Jaejin; Lee, Min-Jae; Wang, Seungsu; In, Kimhong; Galano-Tan, Wilhelm C; Jun, Sanghun; Cho, Kahee; Hwang, Yong-Hwa; Kim, Sung-Ju; Park, Wanje

    2016-03-01

    Cynomolgus monkeys as nonhuman primates are valuable animal models because they have a high level of human gene homology. There are many reference values for hematology and biochemistry of Cynomolgus monkeys that are needed for proper clinical diagnosis and biomedical research conduct. The body weight information and blood type are also key success factors in allogeneic or xenogeneic models. Moreover, the biological parameters could be different according to the origin of the Cynomolgus monkey. However, there are limited references provided, especially of Cambodia origin. In this study, we measured average body weight of 2,518 Cynomolgus monkeys and analyzed hematology and serum biochemistry using 119 males, and determined blood types in 642 monkeys with Cambodia origin. The average body weight of male Cynomolgus monkeys were 2.56±0.345 kg and female group was 2.43±0.330 kg at the age from 2 to 3 years. The male group showed relatively sharp increased average body weight from the 3 to 4 age period compared to the female group. In hematology and biochemistry, it was found that most of the data was similar when compared to other references even though some results showed differences. The ABO blood type result showed that type A, B, AB, and O was approximately 15.6, 33.3, 44.2, and 6.9%, respectively. The main blood type in this facility was B and AB. These biological background references of Cambodia origin could be used to provide important information to researchers who are using them in their biomedical research.

  16. Indocyanine green fluorescence imaging for evaluation of uterine blood flow in cynomolgus macaque.

    Directory of Open Access Journals (Sweden)

    Iori Kisu

    Full Text Available BACKGROUND: Uterine blood flow is an important factor in uterine viability, but the number of blood vessels required to maintain viability is uncertain. In this study, indocyanine green (ICG fluorescence imaging was used to examine uterine hemodynamics and vessels associated with uterine blood flow in cynomolgus macaque. METHODS: The uterus of a female cynomolgus macaque was cut from the vaginal canal to mimic a situation during trachelectomy or uterine transplantation surgery in which uterine perfusion is maintained only with uterine and ovarian vessels. Intraoperative uterine hemodynamics was observed using ICG fluorescence imaging under conditions in which various nutrient vessels were selected by clamping of blood vessels. A time-intensity curve was plotted using imaging analysis software to measure the T(max of uterine perfusion for selected blood vessel patterns. Open surgery was performed with the uterus receiving nutritional support only from uterine vessels on one side. The size of the uterus after surgery was monitored using transabdominal ultrasonography. RESULTS: The resulting time-intensity curves displayed the average intensity in the regions of the uterine corpus and uterine cervix, and in the entire uterus. Analyses of the uterine hemodynamics in the cynomolgus macaque showed that uterine vessels were significantly related to uterine perfusion (P=0.008, whereas ovarian vessels did not have a significant relationship (P=0.588. When uterine vessels were clamped, ovarian vessels prolonged the time needed to reach perfusion maximum. Postoperative transabdominal ultrasonography showed that the size of the uterus was not changed 2 months after surgery, with recovery of periodic menstruation. The cynomolgus macaque has got pregnant with favorable fetus well-being. CONCLUSION: Uterine vessels may be responsible for uterine blood flow, and even one uterine vessel may be sufficient to maintain uterine viability in cynomolgus macaque. Our

  17. Reduced heterotrophy in the stony coral Galaxea fascicularis after life-long exposure to elevated carbon dioxide

    Science.gov (United States)

    Smith, Joy N.; Strahl, Julia; Noonan, Sam H. C.; Schmidt, Gertraud M.; Richter, Claudio; Fabricius, Katharina E.

    2016-01-01

    Ocean acidification imposes many physiological, energetic, structural and ecological challenges to stony corals. While some corals may increase autotrophy under ocean acidification, another potential mechanism to alleviate some of the adverse effects on their physiology is to increase heterotrophy. We compared the feeding rates of Galaxea fascicularis colonies that have lived their entire lives under ocean acidification conditions at natural carbon dioxide (CO2) seeps with colonies living under present-day CO2 conditions. When provided with the same quantity and composition of zooplankton as food, corals acclimatized to high CO2 showed 2.8 to 4.8 times depressed rates of zooplankton feeding. Results were consistent over four experiments, from two expeditions and both in field and chamber measurements. Unless replenished by other sources, reduced zooplankton uptake in G. fascicularis acclimatized to ocean acidification is likely to entail a shortage of vital nutrients, potentially jeopardizing their health and survival in future oceans. PMID:27255977

  18. Transcriptome profiling of Galaxea fascicularis and its endosymbiont Symbiodinium reveals chronic eutrophication tolerance pathways and metabolic mutualism between partners

    Science.gov (United States)

    Lin, Zhenyue; Chen, Mingliang; Dong, Xu; Zheng, Xinqing; Huang, Haining; Xu, Xun; Chen, Jianming

    2017-02-01

    In the South China Sea, coastal eutrophication in the Beibu Gulf has seriously threatened reef habitats by subjecting corals to chronic physiological stress. To determine how coral holobionts may tolerate such conditions, we examined the transcriptomes of healthy colonies of the galaxy coral Galaxea fascicularis and its endosymbiont Symbiodinium from two reef sites experiencing pristine or eutrophied nutrient regimes. We identified 236 and 205 genes that were differentially expressed in eutrophied hosts and symbionts, respectively. Both gene sets included pathways related to stress responses and metabolic interactions. An analysis of genes originating from each partner revealed striking metabolic integration with respect to vitamins, cofactors, amino acids, fatty acids, and secondary metabolite biosynthesis. The expression levels of these genes supported the existence of a continuum of mutualism in this coral-algal symbiosis. Additionally, large sets of transcription factors, cell signal transduction molecules, biomineralization components, and galaxin-related proteins were expanded in G. fascicularis relative to other coral species.

  19. Reduced heterotrophy in the stony coral Galaxea fascicularis after life-long exposure to elevated carbon dioxide

    Science.gov (United States)

    Smith, Joy N.; Strahl, Julia; Noonan, Sam H. C.; Schmidt, Gertraud M.; Richter, Claudio; Fabricius, Katharina E.

    2016-06-01

    Ocean acidification imposes many physiological, energetic, structural and ecological challenges to stony corals. While some corals may increase autotrophy under ocean acidification, another potential mechanism to alleviate some of the adverse effects on their physiology is to increase heterotrophy. We compared the feeding rates of Galaxea fascicularis colonies that have lived their entire lives under ocean acidification conditions at natural carbon dioxide (CO2) seeps with colonies living under present-day CO2 conditions. When provided with the same quantity and composition of zooplankton as food, corals acclimatized to high CO2 showed 2.8 to 4.8 times depressed rates of zooplankton feeding. Results were consistent over four experiments, from two expeditions and both in field and chamber measurements. Unless replenished by other sources, reduced zooplankton uptake in G. fascicularis acclimatized to ocean acidification is likely to entail a shortage of vital nutrients, potentially jeopardizing their health and survival in future oceans.

  20. A new surgical technique of uterine auto-transplantation in cynomolgus monkey: preliminary report about two cases

    OpenAIRE

    KISU, IORI; Mihara, Makoto; BANNO, KOUJI; Hara, Hisako; Yamamoto, Takumi; Araki, Jun; Iida, Takuya; Hayashi, Yohei; Moriguchi, Hisashi; Aoki, Daisuke

    2011-01-01

    Objective Uterine transplantation experiments have been performed in various animal species for future clinical applications of uterine transplantation for permanent uterine factor infertility in humans. The aim of this study was to confirm the feasibility of uterine auto-transplantation in cynomolgus monkeys by developing new surgical techniques. Methods Two female cynomolgus monkeys underwent surgery under general anesthesia. The uterus with vascular grafts and the vaginal wall was removed,...

  1. Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys.

    Science.gov (United States)

    Shimizudani, Takeshi; Nagaoka, Kenjiro; Hanioka, Nobumitsu; Yamano, Shigeru; Narimatsu, Shizuo

    2010-01-05

    Oxidative metabolism of propranolol (PL) enantiomers (R-PL and S-PL) to 4-hydroxypropranolol (4-OH-PL), 5-OH-PL and N-deisopropylpropranolol (NDP) was examined in hepatic microsomes from cynomolgus and marmoset monkeys and in small intestinal microsomes from monkeys and humans. In hepatic microsomes, levels of oxidation activities were similar between the two monkey species, and substrate enantioselectivity (R-PLmicrosomes. In small intestinal microsomes, activity levels were much higher in cynomolgus monkeys than in marmosets and humans and reversed substrate enantioselectivity (R-PL>S-PL) was seen in the formation of NDP in cynomolgus monkeys and humans and in the formation of 5-OH-PL in marmosets. The formation of the three metabolites in cynomolgus monkeys and the formation of NDP in marmosets were biphasic, while the formation of 4-OH-PL in humans was monophasic. From the inhibition experiments using CYP antibodies, CYP2C9 and 2C19 were thought to be involved as N-deisopropylases and CYP2D6 and 3A4 as 4-hydroxylases in human small intestine. Furthermore, CYP1A, 2C and 3A enzymes could be involved in cynomolgus monkeys and CYP2C and 3A enzymes in marmosets. These results indicate that the oxidative profile of PL in hepatic and small intestinal microsomes differ considerably among cynomolgus monkeys, marmosets and humans.

  2. CYP1B1 is polymorphic in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Matsushita, Akinori; Yamazaki, Hiroshi

    2011-09-01

    Cytochrome P450 (CYP) 1B1 is involved in the metabolic activation of various procarcinogens, and some CYP1B1 genetic variants alter CYP1B1-dependent procarcinogen metabolism. Cynomolgus and rhesus macaques are frequently used in toxicity tests due to their evolutionary closeness to humans. In this study, we attempted to identify CYP1B1 genetic variants in 13 cynomolgus and 4 rhesus macaques. A total of 17 genetic variants were identified, including 8 non-synonymous genetic variants, indicating that, similar to humans, CYP1B1 is polymorphic in macaques. These CYP1B1 genetic variants could be the basis for understanding potential inter-animal differences in macaque CYP1B1-dependent metabolism of promutagens.

  3. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Science.gov (United States)

    Hill, F. S.; Cox, A. B.; Salmon, Y. L.; Cantu, A. O.; Lucas, J. N.

    1994-01-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

  4. Ex vivo-expanded cynomolgus macaque regulatory T cells are resistant to alemtuzumab-mediated cytotoxicity

    OpenAIRE

    2013-01-01

    Alemtuzumab (Campath-1H) is a humanized monoclonal antibody (Ab) directed against CD52 that depletes lymphocytes and other leukocytes, mainly by complement-dependent mechanisms. We investigated the influence of alemtuzumab (i) on ex vivo-expanded cynomolgus monkeys regulatory T cells (Treg) generated for prospective use in adoptive cell therapy and (ii) on naturally-occurring Treg following alemtuzumab infusion. Treg were isolated from PBMC and lymph nodes and expanded for two rounds. CD52 ex...

  5. Usefulness of the monkey model to investigate the role soy in postmenopausal women's health.

    Science.gov (United States)

    Appt, Susan E

    2004-01-01

    Some of the important health issues for postmenopausal women include cardiovascular disease, osteoporosis, breast cancer, and relief of menopausal symptoms. Ovariectomized cynomolgus monkeys (Macaca fascicularis) have many strengths as models for research in this area including a close phylogenetic relationship to humans, similarities in lipid/lipoprotein metabolism and coronary artery anatomy, similar skeletal anatomical and morphological characteristics, mammary glands with similar pathophysiological characteristics, and a 28-day menstrual cycle with similar hormonal fluctuations. Monkeys (macaques) also experience declining ovarian function and irregular menstrual cycles (natural menopause) when they approach 24 to 29 yr of age. However, because of their very short life span after natural menopause, ovariectomized macaques are used to model postmenopausal women. The cynomolgus monkey model has been useful in defining the potential cardiovascular benefits of soy foods and soy supplements; however, it remains unclear whether the observations are generalizable to all women or only to those who, like cynomolgus monkeys, convert the soy isoflavone daidzein to the metabolite equol. Particularly important has been the use of the cynomolgus monkey model to understand the effects of soy on breast health. There is evidence from a cynomolgus monkey trial to suggest that soy/soy phytoestrogens have no estrogen agonist effects for breast. Finally, soy/soy phytoestrogens do not appear to be an adequate alternative to postmenopausal hormone therapy. Nevertheless, important attributes of soy have been identified, and it may have potential as a complementary component to hormone therapy.

  6. Molecular ABO phenotyping in cynomolgus macaques using real-time quantitative PCR.

    Science.gov (United States)

    Premasuthan, A; Ng, J; Kanthaswamy, S; Trask, J S; Houghton, P; Farkas, T; Sestak, K; Smith, D G

    2012-10-01

    Macaques are commonly used in biomedical research as animal models of human disease. The ABO phenotype of donors and recipients plays an important role in the success of transplantation and stem cell research of both human and macaque tissue. Traditional serological methods for ABO phenotyping can be time consuming, provide ambiguous results and/or require tissue that is unavailable or unsuitable. We developed a novel method to detect the A, B, and AB phenotypes of macaques using real-time quantitative polymerase chain reaction. This method enables the simple and rapid screening of these phenotypes in macaques without the need for fresh blood or saliva. This study reports the distribution of the A, B, and AB phenotypes of captive cynomolgus macaques that, while regionally variable, closely resembles that of rhesus macaques. Blood group B, as in rhesus macaques, predominates in cynomolgus macaques and its frequency distribution leads to a probability of major incompatibility of 41%. No silencing mutations have been identified in exon 6 or 7 in macaques that could be responsible for the O phenotype, that, although rare, have been reported. The excess homozygosity of rhesus and cynomolgus macaque genotypes in this study, that assumes the absence of the O allele, suggests the possibility of some mechanism preventing the expression of the A and B transferases.

  7. Variation in Clitoral Length in Rhesus Macaques (Macaca mulatta)

    Science.gov (United States)

    Goldschmidt, Beatriz; Cabello, Pedro H; Kugelmeier, Tatiana; Pereira, Barbara B; Lopes, Claudia A; Fasano, Daniele M; Andrade, Marcia C; Santos, Joice S; Marinho, Antonio M

    2009-01-01

    Clitoromegaly in the neonatal period is an important morphologic sign that can be useful for sexual determination in aberrant cases. In rhesus monkeys, differentiation of the external genitalia occurs early during gestation (at 55 to 60 d) and is complete by approximately 80 d. Most of the critical steps in genital differentiation in primates occur prenatally. We sought to determine clitoral size in normal rhesus monkeys (Macaca mulatta) and possible effects of age and inheritance. Clitoral length was highly variable and had no relationship to fertility. Statistical evaluation revealed no association in the distribution of daughters with and without clitoris between mothers with and without clitoris. However, even when mated with several female monkeys, some male macaques produced primarily daughters without clitoris. PMID:19807967

  8. Telomere length of the colonial coral Galaxea fascicularis at different developmental stages

    Science.gov (United States)

    Tsuta, H.; Hidaka, M.

    2013-06-01

    The ability to estimate coral age using soft tissue would be useful for population biology or aging studies on corals. In this study, we investigated whether telomere length can be used to estimate coral age. We applied single telomere length analysis to a colonial coral, Galaxea fascicularis, and estimated telomere lengths of specific coral chromosomes at different developmental stages. If the telomere shortened at each cell division, the telomere length of the coral would be longest in sperm and shortest in adult colonies. However, the mean telomere length of sperm, planula larvae, and polyps was approximately 4 kb, with no significant differences among the developmental stages. The telomerase restriction fragment (TRF) analysis also showed no significant difference in the mean TRF length among the developmental stages. Our results suggested that telomere length is maintained during developmental stages and that estimating the age of colonial coral based on telomere length may not be possible. However, our findings can be used to examine avoidance of aging and rejuvenation during regeneration and asexual reproduction in colonial corals.

  9. Cynomolgus monkey induced pluripotent stem cells established by using exogenous genes derived from the same monkey species.

    Science.gov (United States)

    Shimozawa, Nobuhiro; Ono, Ryoichi; Shimada, Manami; Shibata, Hiroaki; Takahashi, Ichiro; Inada, Hiroyasu; Takada, Tatsuyuki; Nosaka, Tetsuya; Yasutomi, Yasuhiro

    2013-01-01

    Induced pluripotent stem (iPS) cells established by introduction of the transgenes POU5F1 (also known as Oct3/4), SOX2, KLF4 and c-MYC have competence similar to embryonic stem (ES) cells. iPS cells generated from cynomolgus monkey somatic cells by using genes taken from the same species would be a particularly important resource, since various biomedical investigations, including studies on the safety and efficacy of drugs, medical technology development, and research resource development, have been performed using cynomolgus monkeys. In addition, the use of xenogeneic genes would cause complicating matters such as immune responses when they are expressed. In this study, therefore, we established iPS cells by infecting cells from the fetal liver and newborn skin with amphotropic retroviral vectors containing cDNAs for the cynomolgus monkey genes of POU5F1, SOX2, KLF4 and c-MYC. Flat colonies consisting of cells with large nuclei, similar to those in other primate ES cell lines, appeared and were stably maintained. These cell lines had normal chromosome numbers, expressed pluripotency markers and formed teratomas. We thus generated cynomolgus monkey iPS cell lines without the introduction of ecotropic retroviral receptors or other additional transgenes by using the four allogeneic transgenes. This may enable detailed analysis of the mechanisms underlying the reprogramming. In conclusion, we showed that iPS cells could be derived from cynomolgus monkey somatic cells. To the best of our knowledge, this is the first report on iPS cell lines established from cynomolgus monkey somatic cells by using genes from the same species.

  10. In vivo individual variations in pharmacokinetics of efavirenz in cynomolgus monkeys genotyped for cytochrome P450 2C9.

    Science.gov (United States)

    Iwasaki, Kazuhide; Kitsugi, Yusuke; Ikeda, Kanami; Yoshikawa, Takahiro; Hosaka, Shinya; Uehara, Shotaro; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi

    2016-09-01

    Cynomolgus monkeys are used frequently in preclinical studies for new drug development due to their evolutionary closeness to humans. An antiretroviral drug, efavirenz, is a typical probe substrate for human cytochrome P450 (P450) 2B6, but is mainly metabolized by cynomolgus monkey P450 2C9. In this study, plasma concentrations of efavirenz were assessed in six cynomolgus monkeys genotyped for P450 2C9 c.334 A > C (I112L) (three wild-type, one heterozygote and two homozygotes) by high performance liquid chromatography with tandem mass spectrometry. After intravenous administration at a dose of 1.0 mg/kg, biphasic plasma elimination curves of efavirenz were seen in these cynomolgus monkeys. The mean plasma concentration of the primary metabolite 8-hydroxyefavirenz (1 h after treatment, with hydrolysis by β-glucuronidase) in the wild-type group was significantly higher (4.0-fold) than the combined heterozygous and homozygous group mean. The area under the plasma concentration-time curve value of efavirenz in the homozygous group after oral administration at a dose of 2.0 mg/kg was significantly higher (2.0-fold) than the combined wild-type and heterozygous group. These results collectively indicated that P450 2C9 c.334 A > C (I112L) variation was associated with efavirenz metabolic clearance in vivo. Cynomolgus P450 2C9 polymorphism might account for interindividual variations of efavirenz metabolism in cynomolgus monkeys. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Water Flow Affects Zooplankton Feeding by the Scleractinian Coral Galaxea fascicularis on a Polyp and Colony Level

    Directory of Open Access Journals (Sweden)

    Tim Wijgerde

    2012-01-01

    Full Text Available Several factors may affect heterotrophic feeding of benthic marine invertebrates, including water flow rate and polyp context (i.e., the presence of neighbouring polyps. We tested the interactive effects of water flow rate and polyp context on zooplankton feeding by the scleractinian coral Galaxea fascicularis. Single polyps and colonies were incubated in a flow cell for 30 minutes with an ambient Artemia nauplii concentration of 10,000 L−1 and water flow rates ranging from 1.25 to 40 cm s−1. Water flow rate and polyp context showed significant main and interactive effects on feeding rates of G. fascicularis polyps. More specifically, feeding rates were optimal at flow rates of 1.25 cm s−1 for single polyps and 5 to 10 cm s−1 for polyps inhabiting colonies. The presence of epizoic acoelomorph flatworms may have negatively affected the observed feeding rates, especially at high flow. Our results demonstrate that water flow affects coral feeding and thus heterotrophic nutrient input at both a polyp and colony level. These findings are of relevance to our understanding of how biotic and abiotic factors interact on coral heterotrophy and may serve to optimise coral aquaculture.

  12. Effect of Alemtuzumab on Intestinal Intraepithelial Lymphocytes and Intestinal Barrier Function in Cynomolgus Model

    Institute of Scientific and Technical Information of China (English)

    Lin-Lin Qu; Ya-Qing Lyu; Hai-Tao Jiang; Ting Shan; Jing-Bin Zhang; Qiu-Rong Li; Jie-Shou Li

    2015-01-01

    Background:Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia).However,serious infectious complications frequently occur after treatment.The reason for increased infections postalemtuzumab treatment is unknown at this stage.We explore the effect ofalemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.Methods:Twelve male cynomolguses were randomly assigned to either a treatment or control group.The treatment group received alemtuzumab (3 mg/kg,intravenous injection) while the control group received the same volume of physiological saline.Intestinal IELs were isolated from the control group and the treatment group (on day 9,35,and 70 after treatment) for counting and flow cytometric analysis.Moreover,intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.Results:The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 x 108 and 1.35 ± 0.09 × 108,respectively; P < 0.05) and were not fully restored until day 70 after treatment.There were significant differences among four groups considering IELs subtypes.In addition,the proportion ofapoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42,respectively; P < 0.05).Moreover,the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.Conclusions:Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model.The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment.Notably,intestinal barrier function may be disrupted after alemtuzumab treatment.

  13. Effect of Alemtuzumab on Intestinal Intraepithelial Lymphocytes and Intestinal Barrier Function in Cynomolgus Model

    Directory of Open Access Journals (Sweden)

    Lin-Lin Qu

    2015-01-01

    Full Text Available Background: Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia. However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment. Methods: Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay. Results: The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05 and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05. Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment. Conclusions: Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after

  14. Biological properties of neural progenitor cells isolated from the hippocampus of adult cynomolgus monkeys

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells (NPCs) from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro.Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis.Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-βIII-tubulin (Tuj1) and 84% expressed astrocyte specific marker-fibrillary acidic protein (GFAP). In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.

  15. Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV in cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Angie K Marsh

    Full Text Available Cytomegalovirus (CMV is a highly species-specific virus that has co-evolved with its host over millions of years and thus restricting cross-species infection. To examine the extent to which host restriction may prevent cross-species research between closely related non-human primates, we evaluated experimental infection of cynomolgus macaques with a recombinant rhesus macaque-derived CMV (RhCMV-eGFP. Twelve cynomolgus macaques were randomly allocated to three groups: one experimental group (RhCMV-eGFP and two control groups (UV-inactivated RhCMV-eGFP or media alone. The animals were given two subcutaneous inoculations at week 0 and week 8, and a subset of animals received an intravenous inoculation at week 23. No overt clinical or haematological changes were observed and PBMCs isolated from RhCMV-eGFP inoculated animals had comparable eGFP- and IE-1-specific cellular responses to the control animals. Following inoculation with RhCMV-eGFP, we were unable to detect evidence of infection in any blood or tissue samples up to 4 years post-inoculation, using sensitive viral co-culture, qPCR, and Western blot assays. Co-culture of urine and saliva samples demonstrated the presence of endogenous cynomolgus CMV (CyCMV cytopathic effect, however no concomitant eGFP expression was observed. The absence of detectable RhCMV-eGFP suggests that the CyCMV-seropositive cynomolgus macaques were not productively infected with RhCMV-eGFP under these inoculation conditions. In a continued effort to develop CMV as a viral vector for an HIV/SIV vaccine, these studies demonstrate that CMV is highly restricted to its host species and can be highly affected by laboratory cell culture. Consideration of the differences between lab-adapted and primary viruses with respect to species range and cell tropism should be a priority in evaluating CMV as vaccine vector for HIV or other pathogens at the preclinical development stage.

  16. Grooming reciprocity in female tibetan macaques macaca thibetana.

    Science.gov (United States)

    Xia, Dongpo; Li, Jinhua; Garber, Paul A; Sun, Lixing; Zhu, Yong; Sun, Binghua

    2012-06-01

    Grooming among nonhuman primates is widespread and may represent an important service commodity that is exchanged within a biological marketplace. In this study, using focal animal sampling methods, we recorded grooming relationships among 12 adult females in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China, to determine the influence of rank and kinship on grooming relationships, and whether females act as reciprocal traders (exchange grooming received for grooming given) or interchange traders (interchange grooming for social tolerance or other commodities). The results showed that: (1) grooming given was positively correlated with grooming received; (2) kinship did not exert a significant influence on grooming reciprocity; and (3) grooming reciprocity occurred principally between individuals of adjacent rank; however, when females of different rank groomed, females tended to groom up the hierarchy (lower ranking individuals groomed higher ranking individuals more than vice versa). Our results support the contention that both grooming reciprocity and the interchange of grooming for tolerance represent important social tactics used by female Tibetan macaques.

  17. Risk factors for dystocia in pigtailed macaques (Macaca nemestrina).

    Science.gov (United States)

    Stockinger, Diane E; Torrence, Anne E; Hukkanen, Renee R; Vogel, Keith W; Hotchkiss, Charlotte E; Ha, James C

    2011-04-01

    Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources.

  18. A Macaca mulatta model of fulminant hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Ping Zhou; Hong Bu; Jie Xia; Gang Guo; Li Li; Yu-Jun Shi; Zi-Xing Huang; Qiang Lu; Hong-Xia Li

    2012-01-01

    AIM: To establish an appropriate primate model of fulminant hepatic failure (FHF). METHODS: We have, for the first time, established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin. Clinical features, biochemical indexes, histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model. RESULTS: Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration. Coagulation activity was significantly decreased. Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h. The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h, respectively. The autopsy showed typical yellow atrophy of the liver. Hepatic encephalopathy of the models was also confirmed by hepatic coma, MRI and pathological changes of cerebral edema. The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices, imaging and histopathology. CONCLUSION: We have established an appropriate large primate model of FHF, which is closely similar to clinic cases, and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.

  19. Rhesus monkeys (Macaca mulatta) map number onto space.

    Science.gov (United States)

    Drucker, Caroline B; Brannon, Elizabeth M

    2014-07-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance, location, and spacing of the vertical array. We next asked whether monkeys show a spatially-oriented number mapping by testing their responses to the same five-element stimulus array rotated ninety degrees into a horizontal line. In these horizontal probe trials, monkeys preferentially selected the fourth position from the left, but not the fourth position from the right. Our results indicate that rhesus macaques map number onto space, suggesting that the association between number and space in human cognition is not purely a result of cultural experience and instead has deep evolutionary roots.

  20. Molecular mapping of striatal subdivisions in juvenile Macaca Mulata

    Science.gov (United States)

    O’Connor, Joann; Muly, Emil C.; Hemby, Scott E.

    2016-01-01

    The striatum of the primate brain can be subdivided into three distinct anatomical subregions: caudate (CAU), putamen (PUT), and ventral striatum (VS). Although these subregions share several anatomical connections, cell morphological, and histochemical features, they differ considerably in their vulnerability to different neurological and psychiatric diseases, and these brain regions have significantly different functions in health and disease. In order to better understand the molecular underpinnings of the different disease and functional vulnerabilities, transcriptional profiles were generated from the CAU, PUT, and VS of five juvenile rhesus macaques (Macaca mulatta) using human cDNA neuromicroarrays containing triplicate spots of 1227 cDNAs. Differences in microarray gene expression were assessed using z score analysis and 1.5-fold change between paired subregions. Clustering of genes based on dissimilarity of expression patterns between regions revealed subregion specific expression profiles encoding G-protein-coupled receptor signaling transcripts, transcription factors, kinases and phosphatases, and cell signaling and signal transduction transcripts. Twelve transcripts were examined using quantitative real-time PCR (qPCR), and 81% demonstrated alterations similar to those seen with microarray analysis, some of which were statistically significant. Subregion specific transcription profiles support the anatomical differentiation and potential disease vulnerabilities of the respective subregions. PMID:16455077

  1. 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.

  2. Identification and analysis of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 in cynomolgus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Hosaka, Shinya; Yamazaki, Hiroshi

    2014-12-01

    Cytochromes P450 (P450) are important for not only drug metabolism and toxicity, but also biosynthesis and metabolism of cholesterol and bile acids, and steroid synthesis. In cynomolgus macaques, widely used in biomedical research, we have characterized P450 cDNAs, which were isolated as expressed sequence tags of cynomolgus macaque liver. In this study, cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 cDNAs were characterized by sequence analysis, phylogenetic analysis and tissue expression pattern. By sequence analysis, these five cynomolgus P450s had high sequence identities (94-99%) to the human orthologs in amino acids. By phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog as compared with the dog or rat ortholog. By quantitative polymerase chain reaction, among the 10 tissue types, CYP7A1 and CYP17A1 mRNAs were preferentially expressed in liver and adrenal gland, respectively. Cynomolgus CYP27A1 and CYP51A1 mRNAs were most abundantly expressed in liver and testis, respectively. Cynomolgus CYP20A1 mRNA was expressed in all the tissues, including brain and liver. Tissue expression patterns of each cynomolgus P450 were generally similar to that of the human ortholog. These results suggest the molecular similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques and humans.

  3. Ex vivo-expanded cynomolgus macaque regulatory T cells are resistant to alemtuzumab-mediated cytotoxicity.

    Science.gov (United States)

    Dons, E M; Raimondi, G; Zhang, H; Zahorchak, A F; Bhama, J K; Lu, L; Ezzelarab, M; Ijzermans, J N M; Cooper, D K C; Thomson, A W

    2013-08-01

    Alemtuzumab (Campath-1H) is a humanized monoclonal antibody (Ab) directed against CD52 that depletes lymphocytes and other leukocytes, mainly by complement-dependent mechanisms. We investigated the influence of alemtuzumab (i) on ex vivo-expanded cynomolgus monkey regulatory T cells (Treg) generated for prospective use in adoptive cell therapy and (ii) on naturally occurring Treg following alemtuzumab infusion. Treg were isolated from PBMC and lymph nodes and expanded for two rounds. CD52 expression, binding of alemtuzumab and both complement-mediated killing and Ab-dependent cell-mediated cytotoxicity (ADCC) were compared between freshly isolated and expanded Treg and effector T cells. Monkeys undergoing allogeneic heart transplantation given alemtuzumab were monitored for Treg and serum alemtuzumab activity. Ex vivo-expanded Treg showed progressive downregulation of CD52 expression, absence of alemtuzumab binding, minimal change in complement inhibitory protein (CD46) expression and no complement-dependent killing or ADCC. Infusion of alemtuzumab caused potent depletion of all lymphocytes, but a transient increase in the incidence of circulating Treg. After infusion of alemtuzumab, monkey serum killed fresh PBMC, but not expanded Treg. Thus, expanded cynomolgus monkey Treg are resistant to alemtuzumab-mediated, complement-dependent cytotoxicity. Furthermore, our data suggest that these expanded monkey Treg can be infused into graft recipients given alemtuzumab without risk of complement-mediated killing.

  4. 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.

  5. Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Shida, Satomi; Utoh, Masahiro; Murayama, Norie; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-01-01

    1. Cynomolgus monkeys are widely used in preclinical studies as non-human primate species. Pharmacokinetics of human cytochrome P450 probes determined in cynomolgus monkeys after single oral or intravenous administrations were extrapolated to give human plasma concentrations. 2. Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Results of the simplified human PBPK models were consistent with reported experimental PK data in humans or with values simulated by a fully constructed population-based simulator (Simcyp). 3. Oral administrations of metoprolol and dextromethorphan (human P450 2D probes) in monkeys reportedly yielded plasma concentrations similar to their quantitative detection limits. Consequently, ratios of in vitro hepatic intrinsic clearances of metoprolol and dextromethorphan determined in monkeys and humans were used with simplified PBPK models to extrapolate intravenous PK in monkeys to oral PK in humans. 4. These results suggest that cynomolgus monkeys, despite their rapid clearance of some human P450 substrates, could be a suitable model for humans, especially when used in conjunction with simple PBPK models.

  6. Emotional states after grooming interactions in Japanese macaques (Macaca fuscata).

    Science.gov (United States)

    Ueno, Masataka; Yamada, Kazunori; Nakamichi, Masayuki

    2015-11-01

    In animal societies, the effect of grooming interactions on anxiety reduction is unclear. This study examined the effects of giving and receiving grooming on anxiety reduction in free ranging female Japanese macaques (Macaca fuscata) by measuring rates of self-scratching as an index of anxiety. In this study, the authors used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama prefecture, Japan. They evaluated affiliative relationships, which were defined by standard proximity rates, and found that females' self-scratching rates were lower after grooming affiliated partners than during matched-control periods (occurring on another day, beginning at approximately the same time of day as the corresponding postgrooming period) and not after grooming unaffiliated partners. Moreover, regardless of affiliative relationships, self-scratching rates were lower after receiving grooming than during matched-control periods. These findings did not change after excluding data in which groomer and groomee were in proximity after the grooming interaction. In addition, multivariable analysis showed that affiliative relationships, but not kinship or rank distances, were related to differences in the rates of self-scratching between giving grooming and matched-control periods. In contrast, neither affiliative relationships nor kinship nor rank distances affected differences in self-scratching rates between receiving grooming and matched-control periods. Therefore, individuals' anxiety levels decreased both after giving grooming to affiliated partners and after receiving grooming, regardless of affiliative relationships. This is the first empirical study to support the notion that giving grooming to affiliated partners is self-rewarding in Japanese macaques.

  7. Seed dispersal by rhesus macaques Macaca mulatta in Northern India.

    Science.gov (United States)

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

    2014-12-01

    Frugivorous primates are important seed dispersers and their absence from forest patches is predicted to be detrimental to tropical forest regeneration and recruitment. With the reduction of primate populations globally, ecologically resilient primate species, characterized by dietary flexibility and the ability to thrive in a variety of habitats, assume new importance as seed dispersers. The most widely distributed non-human primate, the rhesus macaque Macaca mulatta has been intensively studied but little is known about its role in maintaining ecosystem structure and functions. Due to their frugivorous diet, large group sizes, large home ranges and tolerance to disturbance, rhesus macaques may be effective seed dispersers. We studied seed dispersal by rhesus macaques at the Buxa Tiger Reserve, India, through a combination of behavioural observations and germination experiments. Rhesus macaques dispersed 84% of the 49 species they fed on either through spitting or defecation. Nearly 96% of the handled seeds were undamaged and 61% of the species for which germination tests were performed had enhanced germination. Almost 50% of the monitored seeds among those deposited in situ germinated and 22% established seedlings, suggesting that rhesus macaques are important seed dispersers in tropical forests. Due to their widespread distribution and large populations, rhesus macaques are perceived as common and are categorized as Least Concern on the IUCN Red List, effectively excluding them from any conservation plans. Based on the results of our study, we argue that rhesus macaques fulfill critical ecological functions in their habitat and that this parameter must be taken into consideration when they are reviewed for conservation priorities.

  8. Temporomandibular joint forces measured at the condyle of Macaca arctoides.

    Science.gov (United States)

    Boyd, R L; Gibbs, C H; Mahan, P E; Richmond, A F; Laskin, J L

    1990-06-01

    Forces were measured at the articular surface of the temporomandibular joint (TMJ) condyle in two stump-tail monkeys (Macaca arctoides) during chewing, incisal biting, and drinking and also during aggressive behaviors. Force was measured with a thin piezoelectric foil transducer, which was cemented over the anterior and superior surfaces of the condyle. Wires from the upper and lower surfaces of the foil were insulated between two layers of Teflon tape and run subcutaneously to a telemetry unit, which was implanted in the upper back. Force applied across the foil by the condyle was detected by the telemetry unit and transmitted to an FM radio receiver outside the animal. The FM signals were received and demodulated, and a signal proportional to the force applied between the condyle and the TMJ fossa was displayed on a chart recorder. Data were collected over an 8-day period. The animals were not constrained. The TMJ was found to be load bearing. The greatest force of 39.0 lb (17.7 kg) was measured during feisty vocal aggression. Forces ranged as high as 34.5 lb (15.7 kg) during chewing and 28.5 lb (13.0 kg) during incisal biting. Forces were greater on the working (food) side than on the nonworking (balancing) side by average ratios of 1.4 to 2.6. A large unilateral interference at the most distal molar greatly disturbed chewing. It reduced TMJ forces by 50% or more, and the monkey refused to chew on the side opposite the interference.

  9. Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta)

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Lundsgaard, Jo F. H.; Bakker, Jaco

    2014-01-01

    Five acute-phase reactants—serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron—were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this specie...

  10. Essentialism in the Absence of Language? Evidence from Rhesus Monkeys ("Macaca mulatta")

    Science.gov (United States)

    Phillips, Webb; Shankar, Maya; Santos, Laurie R.

    2010-01-01

    We explored whether rhesus monkeys (Macaca mulatta) share one important feature of human essentialist reasoning: the capacity to track category membership across radical featural transformations. Specifically, we examined whether monkeys--like children (Keil, 1989)--expect a transformed object to have the internal properties of its original…

  11. Proteasome and NF-κB Inhibiting Phaeophytins from the Green Alga Cladophora fascicularis

    Directory of Open Access Journals (Sweden)

    Wenhan Lin

    2007-03-01

    Full Text Available Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1, along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-α induced nuclear factor-κB (NF-κB activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

  12. Establishment of disseminated intravascular coagulation (DIC model by a single iv administration of Escherichia coli-derived lipopolysaccharide (LPS to cynomolgus monkeys and evaluation of its pathophysiological status

    Directory of Open Access Journals (Sweden)

    Hirofumi Minomo

    2017-02-01

    Full Text Available We prepared a DIC model by administrating LPS to cynomolgus monkeys, and investigated its potential for evaluations of new medicines for DIC therapy. Peripheral blood mononuclear cells (PBMC collected from cynomolgus monkeys were incubated with LPS (8 types, and TNF-α levels in the media were measured. LPS from Escherichia coli (K-235 was most appropriate in terms of larger increases and smaller variation in TNF-α levels. PBMC from rats, cynomolgus monkeys or humans were incubated with LPS (K-235, and the TNF-α response to LPS was investigated. The response was comparable between cynomolgus monkeys and humans but small in rats. In an in vivo experiment, LPS (K-235 was administered once intravenously to cynomolgus monkeys with or without recombinant human thrombomodulin (rhTM to investigate any changes in coagulation and fibrinolysis biomarkers and the suppressive effect of rhTM. The liver, kidney, and lung were examined histopathologically. Almost all of the changes resembled the pathophysiological status of human DIC and were suppressed by co-administration of rhTM. The DIC model resembling human DIC was established by LPS (K-235 treatment in cynomolgus monkeys, and therapeutic effect of rhTM was noted, suggesting that this model is useful in evaluations of the efficacy of new medicines for DIC therapy.

  13. Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain.

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Friederike; Hanley, Patrick W; Scott, Dana P; Günther, Stephan; Feldmann, Heinz

    2015-10-01

    In late 2013, the largest documented outbreak of Ebola hemorrhagic fever started in Guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. In March 2014, Ebola virus (EBOV) was identified as the causative agent. This study compares the pathogenesis of a new EBOV strain, Makona, which was isolated in Guinea in 2014 with the prototype strain from the 1976 EBOV outbreak in the former Zaire. Both strains cause lethal disease in cynomolgus macaques with similar pathologic changes and hallmark features of Ebola hemorrhagic fever. However, disease progression was delayed in EBOV-Makona-infected animals, suggesting decreased rather than increased virulence of this most recent EBOV strain.

  14. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

    Directory of Open Access Journals (Sweden)

    Sara C Johnston

    Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

  15. Detection of cynomolgus monkey anti-protein XYZ antibody using immunocapture-LC/MS

    Directory of Open Access Journals (Sweden)

    David Roos

    2016-10-01

    Full Text Available Although enzyme-linked immunosorbent assays and electrochemiluminescence (ECL immunoassays are the most widely used platform for ADA detection, they may be compromised by drug interference. We describe here an alternate, free of drug interference, immunocapture-LC/MS methodology for detecting anti-protein XYZ antibody in cynomolgus monkey plasma. In our approach, ADA-protein XYZ complexes are captured by a mouse monoclonal anti-drug antibody on streptavidin magnetic beads and separated from monkey plasma by a magnet. After elution, ADA are digested with trypsin and detected by LC/MS using a surrogate peptide common to monkey IgG subclasses 1-4. The immunocapture-LC/MS assay was applied to support a toxicology study and results were in close agreement with those from a modified ECL immunoassay. To our knowledge, this is the first application of using LC/MS for monkey ADA detection.

  16. Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

    Directory of Open Access Journals (Sweden)

    James V Lawler

    2006-05-01

    Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

  17. Group A Streptococcus gene expression in humans and cynomolgus macaques with acute pharyngitis.

    Science.gov (United States)

    Virtaneva, Kimmo; Graham, Morag R; Porcella, Stephen F; Hoe, Nancy P; Su, Hua; Graviss, Edward A; Gardner, Tracie J; Allison, James E; Lemon, William J; Bailey, John R; Parnell, Michael J; Musser, James M

    2003-04-01

    The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS.

  18. Bases estructurales de la memoria declarativa. Estudio de la interacción entre la formación del hipocampo y la corteza cerebral en el primate Macaca fascicularis.

    OpenAIRE

    Legidos García, María Ester

    2014-01-01

    La memoria otorga al ser humano una biografía y un conjunto de hechos que le proporciona una identidad, le orienta en el mundo y en su entorno cultural (memoria declarativa). Evidencias clínicas y experimentales muestran que los centros nerviosos cuyo epicentro es el lóbulo temporal medial, son imprescindibles para la consolidación y evocación de los recuerdos. Entre estos centros nerviosos destaca la Formación del Hipocampo (FH) compuesta de giro dentado, campos amónicos CA3, CA2, CA1, subíc...

  19. Extended cleavage specificity of the mast cell chymase from the crab-eating macaque (Macaca fascicularis): an interesting animal model for the analysis of the function of the human mast cell chymase.

    Science.gov (United States)

    Thorpe, Michael; Yu, Jing; Boinapally, Vamsi; Ahooghalandari, Parvin; Kervinen, Jukka; Garavilla, Lawrence de; Hellman, Lars

    2012-12-01

    Serine proteases are the major protein constituents within mast cell secretory granules. These proteases are subdivided into chymases and tryptases depending on their primary cleavage specificity. Here, we present the extended cleavage specificity of the macaque mast cell chymase and compare the specificity with human chymase (HC) and dog chymase (DC) that were produced in the same insect cell expression host. The macaque chymase (MC) shows almost identical characteristics as the HC, including both primary and extended cleavage specificities as well as sensitivity to protease inhibitors, whereas the DC differs in several of these characteristics. Although previous studies have shown that mouse mast cell protease-4 (mMCP-4) is similar in its hydrolytic specificity to the HC, mouse mast cells contain several related enzymes. Thus mice may not be the most appropriate model organism for studying HC activity and inhibition. Importantly, macaques express only one chymase and, as primates, are closely related to human general physiology. In addition, the human and macaque enzymes both cleave angiotensin I (Ang I) in the same way, generating primarily angiotensin II (Ang II) and they do not further degrade the peptide like most rodent enzymes do. Both enzymes also cleave two additional potential in vivo substrates, fibronectin and secretory leukocyte protease inhibitor (SLPI) in a similar way. Given the fact that both HC and MC are encoded by a single gene with high sequence homology and that many physiological processes are similar between these species, the macaque may be a very interesting model to study the physiological role of the chymase and to determine the potency and potential side-effects of various chymase inhibitors designed for therapeutic human use.

  20. 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.

  1. Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host

    Science.gov (United States)

    Okamoto, Munehiro; Miyazawa, Takayuki; Morikawa, Shigeru; Ono, Fumiko; Nakamura, Shota; Sato, Eiji; Yoshida, Tomoyuki; Yoshikawa, Rokusuke; Sakai, Kouji; Mizutani, Tetsuya; Nagata, Noriyo; Takano, Jun-ichiro; Okabayashi, Sachi; Hamano, Masataka; Fujimoto, Koji; Nakaya, Takaaki; Iida, Tetsuya; Horii, Toshihiro; Miyabe-Nishiwaki, Takako; Watanabe, Akino; Kaneko, Akihisa; Saito, Akatsuki; Matsui, Atsushi; Hayakawa, Toshiyuki; Suzuki, Juri; Akari, Hirofumi; Matsuzawa, Tetsuro; Hirai, Hirohisa

    2015-01-01

    We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers. PMID:25743183

  2. Immunochemical detection of cytochrome P450 enzymes in small intestine microsomes of male and female untreated juvenile cynomolgus monkeys.

    Science.gov (United States)

    Uehara, Shotaro; Murayama, Norie; Nakanishi, Yasuharu; Nakamura, Chika; Hashizume, Takanori; Zeldin, Darryl C; Yamazaki, Hiroshi; Uno, Yasuhiro

    2014-09-01

    The expression of small intestinal cytochromes P450 (P450s) has not been systematically measured in cynomolgus monkeys, which are widely used in preclinical drug studies to predict pharmacokinetics and toxicity in humans: therefore, P450 content of small intestine was quantified in 35 cynomolgus monkeys by immunoblotting using 11 selective antibodies. CYP2D, CYP2J2, CYP3A4 and CYP3A5 were detected in all 35 animals, while CYP1A and CYP2C9/19 were detected in 31 and 17 animals, respectively. CYP2C9 and CYP2C19 were detected with the same antibody. CYP1D, CYP2A, CYP2B6, CYP2C76 and CYP2E1 were not detected in any of the 35 animals examined. On analysis of pooled microsomes (35 animals), CYP3A (3A4+3A5) was most abundant (79% of total immunoquantified CYP1-3 proteins), followed by CYP2J2 (13%), CYP2C9/19 (4%), CYP1A (3%) and CYP2D (0.4%). On the analysis of individual microsome samples, each P450 content varied 2-to-6-fold between animals, and no sex differences were observed in any P450 content. These findings should help to increase the understanding of drug metabolism, especially the first-pass effect, in cynomolgus monkey small intestines.

  3. Correlation between formation of the calcarine sulcus and morphological maturation of the lateral ventricle in cynomolgus monkey fetuses.

    Science.gov (United States)

    Fukunishi, Katsuhiro; Sawada, Kazuhiko; Kashima, Masatoshi; Saito, Shigeyoshi; Sakata-Haga, Hiromi; Sukamoto, Takayuki; Aoki, Ichio; Fukui, Yoshihiro

    2011-01-01

    In the present study developmental changes in the cerebral sulci and volumes of subcortical and archicortical structures of the cerebrum in cynomolgus monkey fetuses were examined with T(1)-weighted magnetic resonance (MR) images in 3D. On the embryonic day (ED) 90, the lateral ventricle had still an immature vesicular shape in the occipital region of the cerebrum, and it dramatically closed its lumen by ED 100. In that period the calcarine sulcus progressively infolded from the medial surface of the cerebral hemisphere narrowing the lumen of the lateral ventricle in the occipital region. Volume of the lateral ventricle decreased in the period ED 90-100, increasing afterwards in spite of increasing volumes of subcortical and archicortical structures such as the caudate nucleus, putamen, globus pallidus, amygdala and hippocampal formation. During the same time, the volume of the germinal matrix around lateral ventricles decreased to disappear completely by ED 120. These results suggest that the morphological maturation of lateral ventricle is linked to the development of calcarine sulcus in cynomolgus monkey fetuses. The degree of infolding of calcarine sulcus on ED 100 would be useful as a gross anatomical landmark for evaluating the cerebral maturation in cynomolgus monkey fetuses.

  4. Expression profile of hepatic genes in cynomolgus macaques bred in Cambodia, China, and Indonesia: implications for cytochrome P450 genes.

    Science.gov (United States)

    Ise, Ryota; Nakanishi, Yasuharu; Kohara, Sakae; Yamashita, Hiroyuki; Yoshikawa, Tsuyoshi; Iwasaki, Kazuhide; Nagata, Ryoichi; Fukuzaki, Koichiro; Utoh, Masahiro; Nakamura, Chika; Yamazaki, Hiroshi; Uno, Yasuhiro

    2012-01-01

    Cynomolgus macaques, frequently used in drug metabolism studies, are bred mainly in the countries of Asia; however, comparative studies of drug metabolism between cynomolgus macaques bred in these countries have not been conducted. In this study, hepatic gene expression profiles of cynomolgus macaques bred in Cambodia (mfCAM), China (mfCHN), and Indonesia (mfIDN) were analyzed. Microarray analysis revealed that expression of most hepatic genes, including drug-metabolizing enzyme genes, was not substantially different between mfCAM, mfCHN, and mfIDN; only 1.1% and 3.0% of all the gene probes detected differential expression (>2.5-fold) in mfCAM compared with mfCHN and mfIDN, respectively. Quantitative polymerase chain reaction showed that the expression levels of 14 cytochromes P450 (P450s) important for drug metabolism did not differ (>2.5-fold) in mfCAM, mfCHN, and mfIDN, validating the microarray data. In contrast, expression of CYP2B6 and CYP3A4 differed (>2.5-fold, p profiles, including drug-metabolizing enzyme genes such as P450 genes, are similar in mfCAM, mfCHN, and mfIDN.

  5. Surrogate Mobility and Orientation Affect the Early Neurobehavioral Development of Infant Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Amanda M Dettmer; Ruggerio, Angela M.; Novak, Melinda A.; Meyer, Jerrold S.; Suomi, Stephen J.

    2008-01-01

    A biological mother’s movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard...

  6. Positive reinforcement training as enrichment for singly housed rhesus macaques (Macaca mulatta)

    OpenAIRE

    Baker, KC; Bloomsmith, MA; Neu, K; Griffis, C; Maloney, M.

    2010-01-01

    Positive reinforcement training is one component of behavioural management employed to improve psychological well-being. There has been regulatory promotion to compensate for restricted social housing in part by providing human interaction to singly caged primates, implying an efficacy standard for evaluating human interaction. The effect of positive reinforcement training on the behaviour of 61 singly housed laboratory rhesus macaques (Macaca mulatta) was evaluated at two large primate facil...

  7. Comparative virulence of in vitro-cultured primate- and pig-associated Helicobacter suis strains in a BALB/c mouse and a Mongolian gerbil model.

    Science.gov (United States)

    Bosschem, Iris; Flahou, Bram; Bakker, Jaco; Heuvelman, Edwin; Langermans, Jan A M; De Bruyne, Ellen; Joosten, Myrthe; Smet, Annemieke; Ducatelle, Richard; Haesebrouck, Freddy

    2017-04-01

    Helicobacter suis (H. suis) is the most prevalent gastric non-H. pylori Helicobacter species in humans. This bacterium mainly colonizes the stomach of pigs, but it has also been detected in the stomach of nonhuman primates. The aim of this study was to obtain better insights into potential differences between pig- and primate-associated H. suis strains in virulence and pathogenesis. In vitro-isolated H. suis strains obtained from pigs, cynomolgus monkeys (Macaca fascicularis), and rhesus monkeys (Macaca mulatta) were used for intragastric inoculation of BALB/c mice and Mongolian gerbils. Nine weeks and six months later, samples of the stomach of inoculated and control animals were taken for PCR analysis and histopathological examination. The cynomolgus monkey-associated H. suis strain only colonized the stomach of mice, but not of Mongolian gerbils. All other H. suis strains colonized the stomach in both rodent models. In all colonized animals, severe gastric inflammation was induced. Gastric lymphoid follicles and destruction of the antral epithelium were observed in infected gerbils, but not in mice. Infection with both pig- and primate-associated H. suis strains evoked a similar marked Th17 response in mice and gerbils, accompanied by increased CXCL-13 expression levels. Apart from the cynomolgus monkey-associated strain which was unable of colonizing the stomach of Mongolian gerbils, no substantial differences in virulence were found in rodent models between in vitro-cultured pig-associated, cynomolgus monkey-associated and rhesus monkey-associated H. suis strains. The experimental host determines the outcome of the immune response against H. suis infection, rather than the original host. © 2016 John Wiley & Sons Ltd.

  8. White-cheeked macaque (Macaca leucogenys): A new macaque species from Medog, southeastern Tibet.

    Science.gov (United States)

    Li, Cheng; Zhao, Chao; Fan, Peng-Fei

    2015-07-01

    We describe a newly discovered Macaca species from the Medog, in southeastern Tibet, China, Macaca leucogenys sp. nov or the "white-cheeked macaque". Based on 738 photos taken during direct observations and captured by camera traps this new species appears to be distinct from the Macaca sinica species group. Moreover, the species is distinguished from all potential sympatric macaque species (M. mulatta, M. thibetana, M. assamensis, and M. munzala) in exhibiting a suite of pelage characteristics including relatively uniform dorsal hair pattern, hairy ventral pelage, relative hairless short tail, prominent pale to white side- and chin-whiskers creating a white cheek and round facial appearance, dark facial skin on the muzzle, long and thick hairs on its neck, and a round rather than arrow-shaped male genitalia. This new macaque species was found to exploit a diverse set of habitat types from tropical forest at 1395 m, to primary and secondary evergreen broad-leaved forest at 2000 m, as well as mixed broadleaf-conifer forest at 2700 m. Its range may extend to neighboring counties in Tibet and the part of southeastern Tibet controlled by India. The white-cheeked macaque is threatened by illegal hunting and the construction of hydropower stations. Discovery of this new primate species further highlights the high value for biodiversity conservation of southeastern Tibet and calls for more intensive surveys, studies, and environmental protection in this area.

  9. Spontaneous lesions of the cardiovascular system in purpose-bred laboratory nonhuman primates.

    Science.gov (United States)

    Chamanza, Ronnie; Parry, Nicola M A; Rogerson, Petrina; Nicol, Jen R; Bradley, Alys E

    2006-01-01

    This retrospective study was performed to determine the range, occurrence and incidence of spontaneously arising histopathological findings of the cardiovascular system in purpose-bred laboratory nonhuman primates. Data were collected from 84 controlled toxicological studies with equal numbers of male and female animals and full tissue lists. Attempts were also made to standardize pathological terms used by various original pathologists. Tissue sections from 2464 animals, which included 2050 cynomolgus monkeys (Macaca fascicularis), 284 common marmosets (Callithrix jacchus) and 130 rhesus monkeys (Macaca mulatta) were examined. The most common cardiac finding was focal myocardial inflammation, subcategorized as either "inflammatory cell infiltration" (339) or "focal myocarditis" (131). Other cardiac findings included mineralization (29), endocarditis (16), pericarditis (10), squamous cysts (6) and ectopic thyroid tissue (5). Perivasculitis/vasculitis in the kidney, lung, meninges, sciatic nerve, and other tissues (206) was the most common vascular lesion. Focal myocarditis was more common in male (60%) than female (40%) animals. Cardiac mineralization and extramedullary hematopoiesis were more common in marmosets than other species while ectopic thyroid tissue was present in marmosets and cynomolgus monkeys. To our knowledge, this is the first study to demonstrate the range and incidence of spontaneous cardiovascular lesions in laboratory nonhuman primates.

  10. Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys.

    Science.gov (United States)

    Lee, David C; Varela, Aurore; Kostenuik, Paul J; Ominsky, Michael S; Keaveny, Tony M

    2016-08-01

    Finite element analysis has not yet been validated for measuring changes in whole-bone strength at the hip or spine in people after treatment with an osteoporosis agent. Toward that end, we assessed the ability of a clinically approved implementation of finite element analysis to correctly quantify treatment effects on vertebral strength, comparing against direct mechanical testing, in cynomolgus monkeys randomly assigned to one of three 16-month-long treatments: sham surgery with vehicle (Sham-Vehicle), ovariectomy with vehicle (OVX-Vehicle), or ovariectomy with denosumab (OVX-DMAb). After treatment, T12 vertebrae were retrieved, scanned with micro-CT, and mechanically tested to measure compressive strength. Blinded to the strength data and treatment codes, the micro-CT images were coarsened and homogenized to create continuum-type finite element models, without explicit porosity. With clinical translation in mind, these models were then analyzed for strength using the U.S. Food and Drug Administration (FDA)-cleared VirtuOst software application (O.N. Diagnostics, Berkeley, CA, USA), developed for analysis of human bones. We found that vertebral strength by finite element analysis was highly correlated (R(2)  = 0.97; n = 52) with mechanical testing, independent of treatment (p = 0.12). Further, the size of the treatment effect on strength (ratio of mean OVX-DMAb to mean OVX-Vehicle, as a percentage) was large and did not differ (p = 0.79) between mechanical testing (+57%; 95% CI [26%, 95%]) and finite element analysis (+51% [20%, 88%]). The micro-CT analysis revealed increases in cortical thickness (+45% [19%, 73%]) and trabecular bone volume fraction (+24% [8%, 42%]). These results show that a preestablished clinical finite element analysis implementation-developed for human bone and clinically validated in fracture-outcome studies-correctly quantified the observed treatment effects of denosumab on vertebral strength in cynomolgus monkeys. One

  11. Gene expression analysis of volatile-rich male flowers of dioecious Pandanus fascicularis using expressed sequence tags.

    Science.gov (United States)

    Vinod, M S; Sankararamasubramanian, H M; Priyanka, R; Ganesan, G; Parida, Ajay

    2010-07-15

    Pandanus fascicularis is dioecious with the female plant producing a non-scented fruit while the male produces a flower rich in volatiles. The essential oil extracted from the flowers is economically exploited as a natural flavouring agent as well as for its therapeutic properties. Molecular dissection of this distinct flower for identifying the genes responsible for its aroma by way of expressed sequence tags (ESTs) has not been initiated in spite of its economic viability. A male flower-specific cDNA library was constructed and 977 ESTs were generated. CAP3 analysis performed on the dataset revealed 83 contigs (549 ESTs) and 428 singlets, thereby yielding a total of 511 unigenes. Functional annotation using the BLAST2GO software resulted in 1952 Gene ontology (GO) functional classification terms for 621 sequences. Unknown proteins were further analysed with InterProScan to determine their functional motifs. RNA gel blot analysis of 26 functionally distinct transcripts potentially involved in flowering and volatile generation, using vegetative and reproductive tissues of both the sexes, revealed differential expression profiles. In addition to an overview of genes expressed, candidate genes with expression that are modulated predominantly in the male inflorescence were also identified. This is the first report on generation of ESTs to determine the subset of genes that can be used as potential candidates for future attempts aimed towards its genetic and genome analysis including metabolic engineering of floral volatiles in this economically important plant.

  12. Temporal stability of Symbiodinium phylotype in scleractinian coral Galaxea fascicularis from a tropicalfringing reef in the South China Sea

    Institute of Scientific and Technical Information of China (English)

    ZHOU Guowei; HUANG Hui; DONG Zhijun; YU Ziniu

    2011-01-01

    Symbiodinium sp.occurs in a symbiotic association with various marine invertebrates,including the scleractinian corals.Understanding the flexibility and specificity in coral-algal symbiosis can have important implications for predicting the future of coral reefs in the era of global climate change.In the present study.we conducted Symbiodinium phylotype analysis,based on polymerase chain reaction and restriction fragment length polymorphism ( PCR-RFLP).in the scleractinian coral,Galaxeafascicularis,from a tropical fringing reef in Hainan Island,over a l-yr period.Our results showed that Galaxea fascicularis could associate with Symbiodinium clade C and D either individually or simultaneously.However,during the sampling period,the Symbiodinium phylotype did not change significantly in the scleractinian coral Galaxeafascicularis,although the seawater temperature decreased sharply in the winter season.This study further suggests that the shift in Symbiodinium communities in response to seasonally fluctuating environments might not be a universal feature of coral-algal associations.

  13. Pharmacodynamic model of interleukin-21 effects on red blood cells in cynomolgus monkeys

    DEFF Research Database (Denmark)

    Overgaard, Rune Viig; Karlsson, M.; Ingwersen, S.H.

    2007-01-01

    Interleukin-21 (IL-21) is a novel cytokine that is currently under clinical investigations as a potential anti-cancer agent. Like many other anti-cancer agents, including other interleukins, IL-21 is seen to produce a broad range of biological effects that may be related to both efficacy and safe...... that the structural model presented here can be used for other types of drug induced loss of red blood cells, whereas the mechanism for sampling related blood loss is relevant for investigations of anaemia in all pharmacological studies with smaller animals.......Interleukin-21 (IL-21) is a novel cytokine that is currently under clinical investigations as a potential anti-cancer agent. Like many other anti-cancer agents, including other interleukins, IL-21 is seen to produce a broad range of biological effects that may be related to both efficacy and safety...... of treatment. The present analysis investigates the observed pharmacodynamics effects on red blood cells following various treatment schedules of human IL-21 administrated to cynomolgus monkeys. These effects are described by a novel non-linear mixed-effects model that enabled separation of drug effects...

  14. ABO typing in experimental cynomolgus monkeys using non-invasive methods

    Science.gov (United States)

    Wang, Xiaoxiao; Chen, Song; Chen, Gang

    2017-01-01

    ABH antigens are not expressed on the red blood cells of monkeys, making it difficult to accurately determine their blood type. In this study, we evaluated the feasibility, convenience, and stability of two non-invasive methods for ABO typing (a reverse gel system assay and a buccal mucosal cell immunofluorescent assay) in cynomolgus monkeys (n = 72). The renal tissue immunofluorescent assay was used to obtain an accurate blood type in the monkeys. Using the reverse gel system assay and preabsorbed serum, we achieved accurate detection of ABO blood groups in 65 of the 72 monkeys but obtained confusing results in the remaining 7. The original immunofluorescent staining of the buccal mucosal smears clearly and correctly identified the ABO blood groups in 50 of the 72 monkeys. After repeated smearing and staining, the ABO group type could be correctly identified in samples from the rest of the monkeys, which were either lacking sufficient buccal mucosal cells or contained impurities. Based on our findings, we recommend the reverse gel system assay as the first choice for primate blood type analysis, and the buccal mucosal cell immunofluorescent assay as a Supplementary Method whenever the reverse gel system assay fails to give a clear result. PMID:28112245

  15. Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys.

    Science.gov (United States)

    Reed, Steven G; Coler, Rhea N; Dalemans, Wilfried; Dalemans, Wilifred; Tan, Esterlina V; DeLa Cruz, Eduardo C; Basaraba, Randall J; Orme, Ian M; Skeiky, Yasir A W; Alderson, Mark R; Cowgill, Karen D; Prieels, Jean-Paul; Abalos, Rodolfo M; Dubois, Marie-Claude; Cohen, Joe; Mettens, Pascal; Lobet, Yves

    2009-02-17

    The development of a vaccine for tuberculosis requires a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. We evaluated Mtb72F formulated in AS02A in the cynomolgus monkey model. The vaccine was immunogenic and caused no adverse reactions. When monkeys were immunized with bacillus Calmette-Guérin (BCG) and then boosted with Mtb72F in AS02A, protection superior to that afforded by using BCG alone was achieved, as measured by clinical parameters, pathology, and survival. We observed long-term survival and evidence of reversal of disease progression in monkeys immunized with the prime-boost regimen. Antigen-specific responses from protected monkeys receiving BCG and Mtb72F/AS02A had a distinctive cytokine profile characterized by an increased ratio between 3 Th1 cytokines, IFN-gamma, TNF, and IL-2 and an innate cytokine, IL-6. To our knowledge, this is an initial report of a vaccine capable of inducing long-term protection against tuberculosis in a nonhuman primate model, as determined by protection against severe disease and death, and by other clinical and histopathological parameters.

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

    Science.gov (United States)

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

    2011-02-01

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

  17. Distribution and excretion of arsenic in cynomolgus monkey following repeated administration of diphenylarsinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yayoi [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Negishi, Takayuki [Aoyama Gakuin University, Department of Chemistry and Biological Science, Tokyo (Japan); Mizumura, Ayano; Watanabe, Takayuki [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); Hirano, Seishiro [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); National Institute for Environmental Studies, Research Center for Environmental Risk, Tsukuba, Ibaraki (Japan)

    2008-08-15

    Diphenylarsinic acid (DPAA), a possible product of degradation of arsenic-containing chemical weapons, was detected in well water in Kamisu City, Ibaraki Prefecture, Japan, in 2003. Although some individuals in this area have been affected by drinking DPAA-containing water, toxicological findings on DPAA are limited. To elucidate the mechanism of its toxicity, it is necessary to determine the metabolic behavior of DPAA in the body. In this study, pregnant cynomolgus monkeys at the 50th day of pregnancy were used. The monkeys were treated daily with 1.0 mg DPAA/kg body weight using a nasogastric tube, and the distribution and excretion of arsenic were examined after the repeated administration and 198-237 days after the last administration of DPAA. Fecal excretion was higher than urinary excretion (ca. 3:2 ratio), and arsenic accumulated in the hair and erythrocytes. Distribution of DAPP to plasma and hemolyzed erythrocytes was also examined by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). Two peaks were found in the elution profile of arsenic, due to free and probably protein-bound DPAA. The protein-bound arsenic compounds were presumably trivalent diphenylarsenic compounds, since free DPAA was recovered after treatment of heat-denatured samples with hydrogen peroxide. (orig.)

  18. Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

    Directory of Open Access Journals (Sweden)

    Lei Cai

    2016-01-01

    Full Text Available Models using large animals that are suitable for studying artificial liver support system (ALSS are urgently needed. Presently available acute liver failure (ALF models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization requires either very good surgical skills or multistep processes—even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT. Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr and prothrombin time (PT were significantly increased (all P<0.01 and albumin (ALB was markedly reduced (P<0.01 compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.

  19. Effect of new training technique on affinity of cynomolgus monkeys for animal care personnel.

    Science.gov (United States)

    Nishimoto, Ai; Tachibana, Yuki; Takaura, Kaoru; Ochi, Takehiro; Koyama, Hironari

    2015-01-01

    To confirm our hypothesis that the sex and age of cynomolgus monkeys influences the effect of training, we employed a new training technique designed to increase the animal's affinity for animal care personnel. During 151 days of training, monkeys aged 2 to 10 years accepted each 3 raisins/3 times/day, and communicated with animal care personnel (5 times/day). Behavior was scored using integers between -1 and 5. Before training, 35 of the 61 monkeys refused raisins offered directly by animal care personnel (Score -1, 0 and 1). After training, 28 of these 35 monkeys (80%) accepted raisins offered directly by animal care personnel (>Score 2). The mean score of monkeys increased from 1.2 ± 0.1 to 4.3 ± 0.2. The minimum training period required for monkeys to reach Score 2 was longer for females than for males. After 151 days, 6 of the 31 females and 1 of the 30 males still refused raisins offered directly by animal care personnel. Beneficial effects of training were obtained in both young and adult monkeys. These results indicate that our new training technique markedly improves the affinity of monkeys for animal care personnel, and that these effects tend to vary by sex but not age. In addition, abnormal behavior and symptoms of monkeys were improved by this training.

  20. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    Full Text Available Smallpox, caused by variola virus (VARV, is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  1. Reciprocal interaction between intestinal microbiota and mucosal lymphocyte in cynomolgus monkeys after alemtuzumab treatment.

    Science.gov (United States)

    Li, Q R; Wang, C Y; Tang, C; He, Q; Li, N; Li, J S

    2013-04-01

    It has been known that the gut microbiota plays a central role in shaping normal mucosal immunity, however, little information is available whether the variability of mucosal lymphocytes impacts the commensal flora. Here, we applied a cynomolgus monkey model to characterize the structure and composition of the gut microbiota in response to lymphocyte depletion and to determine their potential association. Molecular profiling of 16S rDNA showed that the intestinal microbiota composition was perturbed after the depletion of mucosal lymphocytes and were recovered following the repopulation. Some specific bacteria from the orders Lactobacillales, Enterobacteriales and Clostridiales, and the genus Prevotella and Faecalibacterium, were primarily responsible for the variations of the gut microbiota after lymphocyte depletion. Interestingly, the species richness of the ileal mucosal microbiota was associated the proportions of TCRαβ+ or TCRγδ+ T cells (pmicrobiota composition after lymphocyte depletion and provide novel evidence that the perturbation of gut microbiota is associated with lymphocyte depletion. It may contribute to understand the relationship between gut commensal microbiota and mucosal immune system. Study results provide insight into biological activity of alemtuzumab in intestinal barrier in organ transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys.

    Science.gov (United States)

    Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

    2016-06-25

    Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine.

  3. Evaluation of the effectiveness and safety of chitosan derivatives as adjuvants for intranasal vaccines.

    Science.gov (United States)

    Kobayashi, Takashi; Fukushima, Kenji; Sannan, Takanori; Saito, Noriko; Takiguchi, Yasuyuki; Sato, Yuko; Hasegawa, Hideki; Ishikawa, Koichi

    2013-04-01

    Intranasal immunization is currently used to deliver live virus vaccines such as influenza. However, to develop an intranasal vaccine to deliver inactivated virus, a safe and effective adjuvant is necessary to enhance the mucosal immune response. Here, we demonstrate the effectiveness of a chitosan microparticle (1-20 μm, 50 kDa, degree of deacetylation=85%) and a cationized chitosan (1000 kDa, degree of deacetylation=85%) derived from natural crab shells as adjuvants for an intranasal vaccine candidate. We examined the effectiveness of chitosan derivatives as an adjuvant by co-administering them with ovalbumin (OVA) intranasally in BALB/c mice, polymeric Ig receptor knockout (pIgR-KO) mice, and cynomolgus monkeys (Macaca fascicularis). pIgR-KO mice were used to evaluate S-IgA production on the mucosal surface without nasal swab collection. Administration of OVA with chitosan microparticles or cationized chitosan induced a high OVA-specific IgA response in the serum of pIgR-KO mice and a high IgG response in the serum of BALB/c mice and cynomolgus monkeys. We also found that administration of chitosan derivatives did not have a detrimental effect on cynomolgus monkeys as determined by complete blood count, blood chemistries, and gross pathology results. These results suggest that chitosan derivatives are safe and effective mucosal adjuvants for intranasal vaccination.

  4. Polymorphic analysis of Mhc-DPB1 gene exon 2 in Tibetan macaques (Macaca thibetana)%藏酋猴 Mhc-DPB1基因 exon2的多态性

    Institute of Scientific and Technical Information of China (English)

    李佳薏; 姚永芳; 周亮; 徐怀亮

    2012-01-01

    主要组织相容性复合体(Major histocompatibility complex,MHC)对许多疾病的易感性和抵抗力起着 重要的作用.为了解藏酋猴(Macaca thibetana)的 MHC 基因遗传背景,以促进藏酋猴遗传资源的保护及其在生 物医学研究中的应用,文章采用 PCR 扩增和克隆测序等方法对来自四川地区的 70 个藏酋猴样品的 Mhc-DPB1 基因 exon 2 进行了检测和分析.首次在藏酋猴中获得了 18 个 DPB1 等位基因(Math-DPB1),其中 1 个为假基因(Math- DPB1*01:06N).18 个等位基因中,Math-DPB1*06:01:01 (67.14%) 的阳性检出率最高,其次为 Math-DPB1*01:03:01 (37.14%)、Math-DPB1*09:02(25.71%)和 Math-DPB1*22:01(15.71%).氨基酸序列比对发现,藏酋猴 Math-DPB1 等位基因编码的氨基酸序列中,有 5 个氨基酸残基变异位点表现出物种特异性.不同物种来源的 DPB1 等位基 因系统发生树表明,藏酋猴、猕猴(Macaca mulatta)和食蟹猴(Macaca fascicularis)的 DPB1 等位基因不是以物种 特异性方式聚类,而是种间混聚在一起,并显示出明显的跨物种多态性(Trans-species polymorphism).选择性检 验表明,平衡选择(Balancing selection)在维持 Math-DPB1 基因的多态性中起着重要的作用.%Major histocompatibility complex (MHC) molecules play an important role in the susceptibility and/or resistance to many diseases. To gain an insight into the MHC background of the Tibetan macaques (Macaca thibetana), and thereby facilitate their protection and application in biomedical research, the second exon of the Mhc-DPBl genes from 70 Tibetan macaques in Sichuan Province were characterized by PCR, cloning, sequencing, and statistical analysis. A total of 18 Mhc-DPB1 alleles were identified from Tibetan macaques, of which one (Math-DPB1* 01:06N) was a pseudogene. Math-DPB1*06:01:01 (67.14%) was the most frequent allele in all the 18 alleles detected, followed by Math-DPBl* 01:03:01 (37.14%), Math-DPB 1*09:02 (25.71%), and Math-DPB 1

  5. Cynomolgus monkey testicular cDNAs for discovery of novel human genes in the human genome sequence

    Directory of Open Access Journals (Sweden)

    Terao Keiji

    2002-12-01

    Full Text Available Abstract Background In order to contribute to the establishment of a complete map of transcribed regions of the human genome, we constructed a testicular cDNA library for the cynomolgus monkey, and attempted to find novel transcripts for identification of their human homologues. Result The full-insert sequences of 512 cDNA clones were determined. Ultimately we found 302 non-redundant cDNAs carrying open reading frames of 300 bp-length or longer. Among them, 89 cDNAs were found not to be annotated previously in the Ensembl human database. After searching against the Ensembl mouse database, we also found 69 putative coding sequences have no homologous cDNAs in the annotated human and mouse genome sequences in Ensembl. We subsequently designed a DNA microarray including 396 non-redundant cDNAs (with and without open reading frames to examine the expression of the full-sequenced genes. With the testicular probe and a mixture of probes of 10 other tissues, 316 of 332 effective spots showed intense hybridized signals and 75 cDNAs were shown to be expressed very highly in the cynomolgus monkey testis, but not ubiquitously. Conclusions In this report, we determined 302 full-insert sequences of cynomolgus monkey cDNAs with enough length of open reading frames to discover novel transcripts as human homologues. Among 302 cDNA sequences, human homologues of 89 cDNAs have not been predicted in the annotated human genome sequence in the Ensembl. Additionally, we identified 75 dominantly expressed genes in testis among the full-sequenced clones by using a DNA microarray. Our cDNA clones and analytical results will be valuable resources for future functional genomic studies.

  6. Competitive inhibition of SGLT2 by tofogliflozin or phlorizin induces urinary glucose excretion through extending splay in cynomolgus monkeys.

    Science.gov (United States)

    Nagata, Takumi; Suzuki, Masayuki; Fukazawa, Masanori; Honda, Kiyofumi; Yamane, Mizuki; Yoshida, Ayae; Azabu, Hiroko; Kitamura, Hidekazu; Toyota, Naoto; Suzuki, Yoshiyuki; Kawabe, Yoshiki

    2014-06-15

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed a glucose lowering effect in type 2 diabetes patients through inducing renal glucose excretion. Detailed analysis of the mechanism of the glucosuric effect of SGLT2 inhibition, however, has been hampered by limitations of clinical study. Here, we investigated the mechanism of urinary glucose excretion using nonhuman primates with SGLT inhibitors tofogliflozin and phlorizin, both in vitro and in vivo. In cells overexpressing cynomolgus monkey SGLT2 (cSGLT2), both tofogliflozin and phlorizin competitively inhibited uptake of the substrate (α-methyl-d-glucopyranoside; AMG). Tofogliflozin was found to be a selective cSGLT2 inhibitor, inhibiting cSGLT2 more strongly than did phlorizin, with selectivity toward cSGLT2 1,000 times that toward cSGLT1; phlorizin was found to be a nonselective cSGLT1/2 inhibitor. In a glucose titration study in cynomolgus monkeys under conditions of controlled plasma drug concentration, both tofogliflozin and phlorizin increased fractional excretion of glucose (FEG) by up to 50% under hyperglycemic conditions. By fitting the titration curve using a newly introduced method that avoids variability in estimating the threshold of renal glucose excretion, we found that tofogliflozin and phlorizin lowered the threshold and extended the splay in a dose-dependent manner without significantly affecting the tubular transport maximum for glucose (TmG). Our results demonstrate the contribution of SGLT2 to renal glucose reabsorption (RGR) in cynomolgus monkeys and demonstrate that competitive inhibition of cSGLT2 exerts a glucosuric effect by mainly extending splay and lowering threshold without affecting TmG.

  7. Phylogeography of Barbary macaques (Macaca sylvanus) and the origin of the Gibraltar colony.

    Science.gov (United States)

    Modolo, Lara; Salzburger, Walter; Martin, Robert D

    2005-05-17

    The Barbary macaque (Macaca sylvanus) is the earliest offshoot of the genus Macaca and the only extant African representative, all other species being Asiatic. Once distributed throughout North Africa, M. sylvanus is now restricted to isolated forest fragments in Algeria and Morocco. The species is threatened; the maximum total wild population size is estimated at 10,000 individuals. Relationships among surviving wild subpopulations in Algeria (96 samples) and Morocco (116 samples) were examined by using 468-bp sequences from hypervariable region I of the mitochondrial DNA control region. Twenty-four different haplotypes were identified, differing by 1-26 mutational steps (0.2-5.6%) and 1 insertion. With one exception (attributable to secondary introduction in coastal Morocco), Algerian and Moroccan haplotypes are clearly distinct. However, whereas Moroccan subpopulations show little divergence in hypervariable region I sequences and little correspondence with geographical distribution, there is a deep division between two main subpopulations in Algeria and one marked secondary division, with haplotypes generally matching geographical distribution. Accepting an origin of the genus Macaca of 5.5 million years ago, the Moroccan population and the two main Algerian subpopulations diverged approximately 1.6 million years ago. Distinction between Moroccan and Algerian haplotypes permitted analysis of the origin of the Gibraltar colony of Barbary macaques (68 samples; 30% of the population). It is generally held that the present Gibraltar population descended from a dozen individuals imported during World War II. However, the Gibraltar sample was found to include Algerian and Moroccan haplotypes separated by at least 16 mutational steps, revealing a dual origin of the founding females.

  8. Differences in the morphology of the maxillary sinus and roots of teeth between Macaca fuscata and Macaca fuscata yakui determined using cone beam computed tomography.

    Science.gov (United States)

    Zaizen, Tomonori; Sato, Iwao; Miwa, Yoko; Sunohara, Masataka; Yosue, Takashi; Mine, Kazuharu; Koseki, Hirohisa; Shimada, Kazuyuki

    2013-01-01

    The Japanese macaque is an endemic species consisting of two subspecies: Macaca fuscata fuscata (MFF) and Macaca fuscata yakui (MFY). The MFY is indigenous to Yakushima Island and represents a subspecies of MFF that lives from Honshu to Shikoku and Kyushu, Japan. However, the differences in the skulls of the MFY and MFF are unknown, despite these subspecies having different skull sizes. The maxillary sinus (MS) indicates that the features of the frontal view reflect the transversal growth of the maxilla of the skull. In this study, we show the MS structures of the MFF (n = 9, 18 sides) and MFY (n = 10, 20 sides) using a cone-beam computed tomography instrument. Base on three-dimensional (3D) reconstructed images the MS and nasal cavity were found to present almost to no significant differences between MFF and MFY. However, we designated three classifications of the sinus floor based on the 3D MS images of these Japanese macaques: a round-like shape (type a, MFF = 66.7% (12/18), MFY = 45% (9/20)), a flat-like shape (type b, MFF = 22.2% (4/18), MFY = 35% (7/20)), and an irregular shape (type c, MFF = 11.1% (2/18), MFY = 20.0% (4/20)). The sinus floor shapes of the MFF were mostly type a, while those of the MFY were mostly type b. The prevalence of a root contacting the cortical bone is higher in the canine (26.7%, (8/30)) and second premolar (20%, (6/30) of the MFY at the nasal cavity, moreover, this value is higher in the third molar (42.9%, (9/21)) of the MS in the MFY. These results suggest that the features of the floor of the MS are related to the differences in maxillary root apices teeth between MMF and MMF.

  9. Elastic modulus of orbicularis oculi muscle in normal humans, humans with Graves' eye disease, and cynomolgus monkeys.

    Science.gov (United States)

    Oestreicher, J H; Frueh, B R

    1995-06-01

    We built an experimental apparatus to investigate the passive elastic characteristics of orbicularis oculi muscle and examined specimens from normal humans, humans with stable Graves' eye disease, and cynomolgus monkeys. Stress-strain curves were determined and found to be exponential. The elastic modulus (Young's modulus), analogous to the stiffness of the material, was calculated as a function of strain. Elastic modulus as a function of instantaneous stress was linear. Monkey elastic modulus values were determined, but did not allow meaningful interspecies comparison because of the small sample size. No significant difference was found between normal humans and humans with Graves' eye disease with respect to elastic modulus values.

  10. Charcot-Leyden crystals: Do they exist in veterinary species? A case report and literature review.

    Science.gov (United States)

    Choi, Eunju; Miller, Andrew D; Devenish, Elizabeth; Asakawa, Makoto; McConkey, Marina; Peters-Kennedy, Jeanine

    2017-08-01

    The Charcot-Leyden crystal (CLC) is a major human eosinophil protein that readily crystallizes; these crystals are common in eosinophilic diseases. Although anecdotal existence of these crystals is known in veterinary pathology, definitive reports do not exist, to our knowledge. We identified eosinophilic crystals in a laryngeal myxosarcoma from a 2-y-old, spayed female, Labrador Retriever dog that were tentatively interpreted as CLCs. However, Ziehl-Neelsen acid-fast stain was negative, arguing against CLCs. The crystals stained red with Masson trichrome, precluding collagen. Periodic acid-Schiff and alcian blue were negative. The crystals stained positively with Okajima, and no myoglobin immunoreactivity was detected, supporting their identity as hemoglobin crystals. In the absence of a hematologic abnormality, these crystals were interpreted to be abnormal hemoglobin breakdown products. Protein sequence comparison was pursued to determine whether a protein similar to CLC exists in mammals. Only 3 nonhuman primate species, the Sumatran orangutan ( Pongo abelii), rhesus macaque ( Macaca mulatta), and cynomolgus monkey ( Macaca fascicularis), had a sequence similarity of >80%. Of the crystal-forming residues, 12 of 54 (22%) were different in the Sumatran orangutan and 15 of 54 (28%) were different in the Macaca spp., which may affect the crystallization process. The lack of reports of CLCs in nonhuman species and our results collectively suggest that CLCs are human-specific.

  11. Molecular detection of Yaba monkey tumour virus from a vervet monkey

    Directory of Open Access Journals (Sweden)

    Helene Brettschneider

    2013-02-01

    Full Text Available Yaba monkey tumour virus (YMTV was first diagnosed in a colony of captive rhesus monkeys (Macaca mulatta in Yaba, Nigeria. It has been implicated as the cause of cutaneous nodules in wild baboons (Papio species, rhesus monkeys (Macaca mulatta and cynomolgus monkeys (Macaca fascicularis. This article reports a case of cutaneous pox lesions caused by YMTV in a  free-ranging  adult  female  vervet  monkey  (Chlorocebus  pygerythrus  from  the  Umkomaas coastal area in South Africa. The virus was identified by molecular sequencing from fragments of the insulin metalloprotease-like protein and intracellular mature virion membrane protein as well as the DNA polymerase genes. Phylogenetic analyses of these gene regions revealed a 99% similarity of the sample to YMTV. Although human disease caused by YMTV is normally mild,  it  is  recommended  that  persons  in  contact  with  non-human  primates  in  the  area  of Umkomaas who develop cutaneous lesions should inform their doctors of the possibility of this infection. The extent and significance of the virus to human and non-human primates in South Africa are not known. To the authors’ knowledge, this is the first diagnosis of YMTV in South Africa and in vervet monkeys.

  12. A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys, Cynomolgus Macaques, and Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Donald K. Nichols

    2012-10-01

    Full Text Available Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV Boniface in non-human primates (NHP belonging to three different species. Groups of cynomolgus macaques (cyno, rhesus macaques (rhesus, and African green monkeys (AGM were challenged with target doses of 50 or 500 plaque-forming units (pfu of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT and aspartate transaminase (AST concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.

  13. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

    Science.gov (United States)

    Lin, Philana Ling; Maiello, Pauline; Gideon, Hannah P; Coleman, M Teresa; Cadena, Anthony M; Rodgers, Mark A; Gregg, Robert; O'Malley, Melanie; Tomko, Jaime; Fillmore, Daniel; Frye, L James; Rutledge, Tara; DiFazio, Robert M; Janssen, Christopher; Klein, Edwin; Andersen, Peter L; Fortune, Sarah M; Flynn, JoAnne L

    2016-07-01

    Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT) of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF) neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26) before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25). Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.

  14. Behavioural profiles in captive-bred cynomolgus macaques: towards monkey models of mental disorders?

    Directory of Open Access Journals (Sweden)

    Sandrine M J Camus

    Full Text Available BACKGROUND: To date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. The laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored. METHODS: The present study, therefore, aimed at investigating the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 cynomolgus macaques in captive conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence analysis and a hierarchical clustering. RESULTS: The study identified five distinct profiles (groups A to E that significantly differed on several behaviours, body postures, body orientations, gaze directions and locations in the cage environment. We suggest that animals from the low n groups (D and E present depressive-like and anxious-like symptoms, reminiscent of depressive and generalized anxiety disorders. Inter-individual differences were highlighted through unbiased ethological observations of spontaneous behaviours and associated parameters, although these were not associated with differences in plasma or cerebrospinal fluid levels of either stress-related hormones or monoamines, i.e. in accordance with the human situation. CONCLUSIONS: No interventional behavioural testing was required to discriminate between 3 typical and 2 atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like and anxiety-like symptoms. The use of unbiased behavioural observations might, thus, allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.

  15. Behavioural Profiles in Captive-Bred Cynomolgus Macaques: Towards Monkey Models of Mental Disorders?

    Science.gov (United States)

    Camus, Sandrine M. J.; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

    2013-01-01

    Background To date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. The laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored. Methods The present study, therefore, aimed at investigating the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 cynomolgus macaques in captive conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence analysis and a hierarchical clustering. Results The study identified five distinct profiles (groups A to E) that significantly differed on several behaviours, body postures, body orientations, gaze directions and locations in the cage environment. We suggest that animals from the low n groups (D and E) present depressive-like and anxious-like symptoms, reminiscent of depressive and generalized anxiety disorders. Inter-individual differences were highlighted through unbiased ethological observations of spontaneous behaviours and associated parameters, although these were not associated with differences in plasma or cerebrospinal fluid levels of either stress-related hormones or monoamines, i.e. in accordance with the human situation. Conclusions No interventional behavioural testing was required to discriminate between 3 typical and 2 atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like and anxiety-like symptoms. The use of unbiased behavioural observations might, thus, allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups. PMID:23658620

  16. Chronic Ketamine Exposure Causes White Matter Microstructural Abnormalities in Adolescent Cynomolgus Monkeys

    Directory of Open Access Journals (Sweden)

    Qi Li

    2017-05-01

    Full Text Available Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control was administered intravenously for 3 months to male adolescent cynomolgus monkeys (n = 5/group. Diffusion tensor imaging (DTI experiments were performed and tract-based spatial statistics (TBSS was used for data analysis. Fractional anisotropy (FA was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR, retrolenticular limb of the internal capsule (RLIC and superior longitudinal fasciculus (SLF, and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.

  17. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis

    Science.gov (United States)

    Lin, Philana Ling; Maiello, Pauline; Gideon, Hannah P.; Cadena, Anthony M.; Rodgers, Mark A.; Gregg, Robert; O’Malley, Melanie; Fillmore, Daniel; Frye, L. James; Rutledge, Tara; DiFazio, Robert M.; Janssen, Christopher; Klein, Edwin; Andersen, Peter L.; Fortune, Sarah M.; Flynn, JoAnne L.

    2016-01-01

    Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT) of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF) neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26) before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25). Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection. PMID:27379816

  18. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Philana Ling Lin

    2016-07-01

    Full Text Available Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26 before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25. Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.

  19. Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

    Science.gov (United States)

    Fellows, Patricia; Price, Jessica; Martin, Shannon; Metcalfe, Karen; Krile, Robert; Barnewall, Roy; Hart, Mary Kate; Lockman, Hank

    2015-09-01

    The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 μg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Construction of an integrated welfare assessment system (MacWel) for Macaques (Macaca spp.) in human husbandry

    DEFF Research Database (Denmark)

    Kirchner, Marlene; Bakker, Jaco

    2015-01-01

    The paper describes the construction procedure of an assessment protocol for Macaques (Macaca spp.). The authors have chosen an integrative approach, currently frequently used for the construction of such protocols with a clear preference for animal-based parameters to assess the welfare states o...

  1. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

    Science.gov (United States)

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g. dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially-housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration (180 words). PMID:25488714

  2. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kelly, K R; Pypendop, B H; Christe, K L

    2015-08-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post-tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration.

  3. Effects of age and sex on the hematology and blood chemistry of Tibetan macaques (Macaca thibetana).

    Science.gov (United States)

    Wu, Di; Yi, Yong; Sun, Fei; Zhou, Liang; Yang, Feng; Wang, Hongxing; Zhang, Guodong; Zhang, Yu Alex; Yue, Feng

    2014-01-01

    Tibetan macaques (Macaca thibetana), also known as Chinese stump-tailed macaques, are a threatened primate species. Although Tibetan macaques are Old World monkeys in the genus of Macaca, limited age- and sex-related physiologic data are available for this particular species. We used 69 apparently healthy Tibetan male and female macaques to explore the effect of age and sex on physiologic parameters. Somatometric measurements, biochemistry, and hematologic parameters were analyzed. Significant age-related differences were found for weight, BMI, RBC count, Hgb, Hct, neutrophils, eosinophil count, ALT, AST, ALP, GGT, creatine kinase (muscle and brain subtypes), LDH, α-amylase, creatinine, apolipoprotein A1, total protein, albumin, cholesterol, HDL, and potassium. Significant differences by sex were noted for weight, BMI, ALT, total bilirubin, and indirect bilirubin. An interaction between age and sex accounted for statistically significant differences in the values for weight, BMI, and lymphocyte and eosinophil counts. These physiologic data will provide veterinarians and researchers with important age- and sex-specific reference ranges for evaluating experimental results from Tibetan macaques.

  4. Neurons in the brain of the male cynomolgus monkey accumulate /sup 3/H-medroxyprogesterone acetate (MPA)

    Energy Technology Data Exchange (ETDEWEB)

    Michael, R.P.; Bonsall, R.W.; Rees, H.D.

    1986-03-01

    MPA is a synthetic progestin with androgen-depleting activity. It is used clinically to reduce sexual motivation and aggression in male sex offenders. The mechanisms for its behavioral effects are not known. The authors used steroid autoradiography to help identify sites where MPA may act in the brain of male primates. Twenty-four hours after castration, two adult male cynomolgus macaques, weighing 4.9 and 6.6 kg, were administered 5 mCi /sup 3/H-MPA (NEN, 47.7 Ci/mmol) i.v., and were killed 1 h later. Left sides of the brains and samples of pituitary glands were frozen and 4-micron sections were cut and processed for thaw-mount autoradiography. Radioactivity was concentrated in the nuclei of many neutrons in the ventromedial hypothalamic nucleus (n.), arcuate n., medial preoptic n., and anterior hypothalamic area. Virtually no labeled cells were seen in the bed n. of stria terminalis, lateral septal n., amygdala, or pituitary gland. Right sides of the brains were analyzed by HPLC which demonstrated that 98% of the radioactivity in cell nuclei from the hypothalamus was in the form of unmetabolized /sup 3/H-MPA. The distribution of labelling in the brain following /sup 3/H-MPA administration resembled that previously seen following /sup 3/H-ORG 2058 in female cynomolgus monkeys. These data indicate that MPA has a circumscribed localization in the brain.

  5. The Success Rate in a Complicated Spatial Memory Test Is Determined by Age, Sex, Life History and Search Strategies in Cynomolgus Monkeys

    DEFF Research Database (Denmark)

    Darusman, Huda S; Kalliokoski, Otto; Sajuthi, Dondin

    2014-01-01

    In a retrospective analysis of data from three studies using a delayed response task in cynomolgus monkeys, we examined the subjects' search patterns and success rates. Twenty-seven monkeys of both sexes, divided into three age groups, were tasked with retrieving two food items hidden in an array...

  6. NCBI nr-aa BLAST: CBRC-MDOM-05-0060 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-05-0060 ref|NP_001123902.1| toll-like receptor 6 [Macaca mulatta] dbj|BAG55054.1| toll...-like receptor 6 [Macaca fascicularis] dbj|BAG55055.1| toll-like receptor 6 [Macaca mulatta] NP_001123902.1 0.0 62% ...

  7. NCBI nr-aa BLAST: CBRC-MMUR-01-1015 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-1015 ref|NP_001123902.1| toll-like receptor 6 [Macaca mulatta] dbj|BAG55054.1| toll...-like receptor 6 [Macaca fascicularis] dbj|BAG55055.1| toll-like receptor 6 [Macaca mulatta] NP_001123902.1 0.0 85% ...

  8. NCBI nr-aa BLAST: CBRC-OPRI-01-0286 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-0286 ref|NP_001123902.1| toll-like receptor 6 [Macaca mulatta] dbj|BAG55054.1| toll...-like receptor 6 [Macaca fascicularis] dbj|BAG55055.1| toll-like receptor 6 [Macaca mulatta] NP_001123902.1 0.0 72% ...

  9. NCBI nr-aa BLAST: CBRC-MLUC-01-0960 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0960 ref|NP_001123902.1| toll-like receptor 6 [Macaca mulatta] dbj|BAG55054.1| toll...-like receptor 6 [Macaca fascicularis] dbj|BAG55055.1| toll-like receptor 6 [Macaca mulatta] NP_001123902.1 0.0 82% ...

  10. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques.

    Science.gov (United States)

    Schwartz, Jennifer A; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K; Gallo, Robert C; DeVico, Anthony L; Fouts, Timothy R

    2016-07-01

    A promising concept for human immunodeficiency virus (HIV) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the HIV glycoprotein gp120 binds to its receptor, CD4. We are developing chimeric antigens (full-length single chain, or FLSC) in which gp120 and CD4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (A. DeVico et al., Proc Natl Acad Sci U S A 104:17477-17482, 2007, doi:10.1073/pnas.0707399104; T. R. Fouts et al., J Virol 74:11427-11436, 2000, doi:10.1128/JVI.74.24.11427-11436.2000). Proof of concept studies with nonhuman primates show that FLSC elicited heterologous protection against simian-human immunodeficiency virus (SHIV)/simian immunodeficiency virus (SIV) (T. R. Fouts et al., Proc Natl Acad Sci U S A 112:E992-E999, 2016, doi:10.1073/pnas.1423669112), which correlated with antibodies against transition state gp120 epitopes. Nevertheless, advancement of any vaccine that comprises gp120-CD4 complexes must consider whether the CD4 component breaks tolerance and becomes immunogenic in the autologous host. To address this, we performed an immunotoxicology study with cynomolgus macaques vaccinated with either FLSC or a rhesus variant of FLSC containing macaque CD4 sequences (rhFLSC). Enzyme-linked immunosorbent assay (ELISA) binding titers, primary CD3(+) T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4(+) T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures

  11. Pharmacokinetics and biodistribution of a human monoclonal antibody to oxidized LDL in cynomolgus monkey using PET imaging.

    Directory of Open Access Journals (Sweden)

    Amrita V Kamath

    Full Text Available PURPOSE: Oxidized low-density lipoprotein (LDL plays an essential role in the pathogenesis of atherosclerosis. The purpose of this study was to characterize the pharmacokinetics (PK of a human recombinant IgG1 antibody to oxidized LDL (anti-oxLDL in cynomolgus monkey. The tissue biodistribution of anti-oxLDL was also investigated using positron emission tomography (PET imaging. METHODS: Anti-oxLDL was conjugated with the N-hydroxysuccinimide ester of DOTA (1,4,7,10-tetraazacyclododecane 1,4,7,10-tetraacetic acid and radiolabeled by chelation of radioactive copper-64 ((64Cu for detection by PET. Anti-oxLDL was administered as a single intravenous (IV dose of 10 mg/kg (as a mixture of radiolabeled and non-labeled material to two male and two female cynomolgus monkeys. Serum samples were collected over 29 days. Two ELISA methods were used to measure serum concentrations of anti-oxLDL; Assay A was a ligand binding assay that measured free anti-oxLDL (unbound and partially bound forms and Assay B measured total anti-oxLDL. The biodistribution was observed over a 48-hour period following dose administration using PET imaging. RESULTS: Anti-oxLDL serum concentration-time profiles showed a biphasic elimination pattern that could be best described by a two-compartment elimination model. The serum concentrations obtained using the two ELISA methods were comparable. Clearance values ranged from 8 to 17 ml/day/kg, while beta half-life ranged from 8 to 12 days. The initial volume of distribution and volume of distribution at steady state were approximately 55 mL/kg and 150 mL/kg, respectively. PET imaging showed distribution predominantly to the blood pool, visible as the heart and great vessels in the trunk and limbs, plus diffuse signals in the liver, kidney, spleen, and bone marrow. CONCLUSIONS: The clearance of anti-oxLDL is slightly higher than typical IgG1 antibodies in cynomolgus monkeys. The biodistribution pattern appears to be consistent with an

  12. Recruitment and monitoring behaviors by leaders predict following in wild Barbary macaques (Macaca sylvanus

    Directory of Open Access Journals (Sweden)

    A. Seltmann

    2016-07-01

    collective movements in a group of wild Barbary macaques (Macaca sylvanus in the Middle Atlas, Morocco. The number of individuals displaying pre-departure behavior predicted the success of an initiation of a collective movement. Pauses of the first departing individual after departure enhanced following behavior and might have served as recruitment signal. However, the opposite was the case for back-glancing, which functions as a monitoring signal in other species. Because in our study frequently back-glancing individuals were also less socially integrated, back glances may better be interpreted as indicators of hesitation and insecurity. To successfully initiate a collective movement, it seemed to be sufficient for a socially integrated group member to take action when other group members signal their willingness prior to departure and to occasionally wait for the group while moving.

  13. Rosalie: the brazilian female monkey of Charcot Rosalie: a pequenina macaca brasileira de Charcot

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    Hélio A.G. Teive

    2005-09-01

    Full Text Available Jean-Martin Charcot, the father of Neurology, a very austere and reserved man that did not express affection freely for human being, had a profound affection to animals, particularly to a small female monkey, called "Rosalie", which came from Brazil and was a gift of Dom Pedro II to Charcot.Jean-Martin Charcot, considerado o pai da Neurologia, foi um homem de aspecto austero e reservado, que tinha dificuldades de expressar os seus sentimentos para outros seres humanos. Contudo ele tinha profunda afeição por animais, particularmente por uma pequena macaca, chamada de "Rosalie", oriunda do Brasil e que foi um presente dado a ele por Dom Pedro II.

  14. Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta)

    Science.gov (United States)

    Stone, W. H.; Saphire, D. G.; Hackleman, S. M.; Braun, A. M.; Pennington, P.; Scheffler, J.; Wigle, J. C.; Cox, A. B.

    1994-01-01

    We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure to protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age.

  15. Effects of feeding selenium deficient diets to rhesus monkeys (Macaca Mulatta)

    Energy Technology Data Exchange (ETDEWEB)

    Butler, J.A.; Whanger, P.D.; Patton, N.M.

    1988-02-01

    Pregnant rhesus monkeys (Macaca mulatta) were fed either selenium (Se) deficient or Se supplemented diets with adequate vitamin E. Except for some cardiac irregularities in the first babies born to these females, no physiological disorders due to Se deficiency were seen in a subsequent offspring. Plasma and erythrocyte glutathione peroxidase activities and blood Se levels increased in the Se supplemented monkeys but decreased in the deficient ones. The data indicated that hair Se levels reflect long term exposure to this element. In a very preliminary experiment, evidence was obtained to indicate that dietary protein deficiency along with Se deficiency will generate cardiomyopathic lesions characteristic of Se deficiency. It is hypothesized that, in addition to Se deficiency, another dietary deficiency (or abnormality) is necessary to produce Se deficiency lesions in higher primates. Higher glutathione transferase (or non-Se glutathione peroxidase) activity in tissues of rhesus monkeys may account for this resistance.

  16. Campylobacter pylori isolated from the stomach of the monkey, Macaca nemestrina.

    Science.gov (United States)

    Bronsdon, M A; Schoenknecht, F D

    1988-09-01

    Campylobacter pylori was isolated from the gastric mucosa in 6 of 24 pigtailed macaques (Macaca nemestrina) examined by gastric biopsy and culture; 3 isolates were recovered during gastroendoscopy, and 3 were recovered at necropsy. The isolates were morphologically and biochemically similar to the human type strain NCTC 11638, differing only in colony diameter, pigmentation, and rate of growth. Identity of the isolates was confirmed by whole-genomic DNA-DNA hybridization with the type strain. Colonization of the monkey stomachs was associated with hypochlorhydria and histologic features resembling type B chronic gastritis in humans. Host animals exhibited no morbid clinical effects of colonization, although endoscopy revealed inflammation, erythema, and friable tissue in some animals. The discovery of C. pylori occurring spontaneously in M. nemestrina extends the known range of the hosts of the organism and offers the possibility of a natural or experimental model of the infection in monkeys.

  17. The spatiotemporal expression changes of 16 epididymis-specific genes induced by testosterone, heat, and combination treatment in cynomolgus monkey

    Institute of Scientific and Technical Information of China (English)

    Xiangqi Li; Qiang Liu; Shigui Liu; Xuesen Zhang; Yixun Liu; Yonglian Zhang

    2008-01-01

    The experimental infertility model of treatments involving testicular warming, testosterone implant, and a combination of the two was developed to confirm a synergistic action induced by the combination treatment on germ cell apoptosis in cynomolgus monkey testis. Using this model, the spatio-temporal expression changes of 16 reported or novel genes in epididymis were investigated to examine the treatment's effect on epididymal genes.It was demonstrated that these region-specific genes,some of which were not regionally fixed,changed greatly with these treatments.The expression levels of these epididymal gemes fluctuated,and the expression of most of the genes returned to nearly normal level at the end of treatments.Moreover,the expression changes resulting from the combination treatment has an antagonistic action on the expression of epididymal genes and that is effect is not as adverse on epididy mis as that of the two single treatments.

  18. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges.

    Science.gov (United States)

    Grant-Klein, Rebecca J; Altamura, Louis A; Badger, Catherine V; Bounds, Callie E; Van Deusen, Nicole M; Kwilas, Steven A; Vu, Hong A; Warfield, Kelly L; Hooper, Jay W; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2015-01-01

    Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed.

  19. Impact of human pressure and forest fragmentation on the Endangered Barbary macaque Macaca sylvanus in the Middle Atlas of Morocco

    OpenAIRE

    Ménard, Nelly; Rantier, Yann; Foulquier, Adrien; Qarro, Mohamed; Chillasse, Lahcen; Vallet, Dominique; Pierre, Jean-Sébastien; Butet, Alain

    2014-01-01

    International audience; Overexploitation of forests by humans can lead to highly fragmented populations of forest-dependent species that have poor dispersal abilities. We tested the influence of habitat quality, landscape structure and human pressure on densities of the Barbary macaque Macaca sylvanus in the largest wild population, in the Middle Atlas of Morocco. We surveyed 14 forest fragments of 5-142 km2 that are separated from each other by an inhospitable matrix. We estimated the habita...

  20. Depressive-like behavioural profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

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    Sandrine MJ Camus

    2014-02-01

    Full Text Available Background: To unravel the causes of major depressive disorder (MDD, the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored.Methods: Behavioural data (including body postures, orientations, gaze directions, inter-individual distances and locations in the cage were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys.Results: Consistent with our previous studies, we found depressive-like characteristics (e.g. inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles.Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a spontaneous model of depressive disorders.

  1. Depressive-like behavioral profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

    Science.gov (United States)

    Camus, Sandrine M. J.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

    2014-01-01

    Background: To unravel the causes of major depressive disorder (MDD), the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament, or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored. Methods: Behavioral data (including body postures, orientations, gaze directions, inter-individual distances, and locations in the cage) were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys. Results: Consistent with our previous studies, we found depressive-like characteristics (e.g., inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall) among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles. Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a “spontaneous” model of depressive disorders. PMID:24600363

  2. Pre-incubation with cyclosporine A potentiates its inhibitory effects on pitavastatin uptake mediated by recombinantly expressed cynomolgus monkey hepatic organic anion transporting polypeptide.

    Science.gov (United States)

    Takahashi, Tsuyoshi; Ohtsuka, Tatsuyuki; Uno, Yasuhiro; Utoh, Masahiro; Yamazaki, Hiroshi; Kume, Toshiyuki

    2016-11-01

    Cyclosporine A, an inhibitor of hepatic organic anion transporting polypeptides (OATPs), reportedly increased plasma concentrations of probe substrates, although its maximum unbound blood concentrations were lower than the experimental half-maximal inhibitory (IC50 ) concentrations. Pre-incubation with cyclosporine A in vitro before simultaneous incubation with probes has been reported to potentiate its inhibitory effects on recombinant human OATP-mediated probe uptake. In the present study, the effects of cyclosporine A and rifampicin on recombinant cynomolgus monkey OATP-mediated pitavastatin uptake were investigated in pre- and simultaneous incubation systems. Pre-incubation with cyclosporine A, but not with rifampicin, decreased the apparent IC50 values on recombinant cynomolgus monkey OATP1B1- and OATP1B3-mediated pitavastatin uptake. Application of the co-incubated IC50 values toward R values (1 + [unbound inhibitor]inlet to the liver, theoretically maximum /inhibition constant) in static models, 1.1 in monkeys and 1.3 in humans, for recombinant cynomolgus monkey and human OATP1B1-mediated pitavastatin uptake might result in the poor prediction of drug interaction magnitudes. In contrast, the lowered IC50 values after pre-incubation with cyclosporine A provided better prediction with R values of 3.9 for monkeys and 2.7 for humans when the estimated maximum cyclosporine A concentrations at the inlet to the liver were used. These results suggest that the enhanced inhibitory potential of perpetrator medicines by pre-incubation on cynomolgus monkey OATP-mediated pitavastatin uptake in vitro could be of value for the precise estimation of drug interaction magnitudes in silico, in accordance with the findings from pre-administration of inhibitors on pitavastatin pharmacokinetics validated in monkeys. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Akira Yano

    2015-01-01

    Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

  4. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Patricia C., E-mail: ryanp@medimmune.com [MedImmune, LLC, Gaithersburg, MD (United States); Sleeman, Matthew A. [MedImmune, LLC, Cambridge (United Kingdom); Rebelatto, Marlon [MedImmune, LLC, Gaithersburg, MD (United States); Wang, Bing; Lu, Hong [MedImmune, LLC, Moutain View, CA (United States); Chen, Xiaomin [Novartis, East Hanover, NJ (United States); Wu, Chi-Yuan [MedImmune, LLC, Moutain View, CA (United States); Hinrichs, Mary Jane; Roskos, Lorin [MedImmune, LLC, Gaithersburg, MD (United States); Towers, Heidi [MedImmune, LLC, Cambridge (United Kingdom); McKeever, Kathleen; Dixit, Rakesh [MedImmune, LLC, Gaithersburg, MD (United States)

    2014-09-01

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys.

  5. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Hill, F.S.; Cantu, A.O.; Lucas, J.N. (Lawrence Livermore National Lab., CA (United States)); Cox, A.B.; Salmon, Y.L. (Air Force Armstrong Lab., Brookes AFB, TX (United States))

    1994-10-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 [mu]g/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) that that produced by PHA (M1<0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture. (author).

  6. Surgical correction of an arteriovenous fistula in a ring-tailed lemur (Lemur catta).

    Science.gov (United States)

    Boedeker, Nancy C; Guzzetta, Philip; Rosenthal, Steven L; Padilla, Luis R; Murray, Suzan; Newman, Kurt

    2014-02-01

    A 10-y-old ovariohysterectomized ring-tailed lemur (Lemur catta) was presented for exacerbation of respiratory signs. The lemur had a history of multiple examinations for various problems, including traumatic lacerations and recurrent perivulvar dermatitis. Examination revealed abnormal lung sounds and a femoral arteriovenous fistula with a palpable thrill and auscultable bruit in the right inguinal area. A diagnosis of congestive heart failure was made on the basis of exam findings, radiography, abdominal ultrasonography, and echocardiography. The lemur was maintained on furosemide until surgical ligation of the fistula was performed. Postoperative examination confirmed successful closure of the fistula and resolution of the signs of heart failure. Arteriovenous fistulas are abnormal connections between an artery and a vein that bypass the capillary bed. Large arteriovenous fistulas may result in decreased peripheral resistance and an increase in cardiac output with consequent cardiomegaly and high output heart failure. This lemur's high-flow arteriovenous fistula with secondary heart failure may have been iatrogenically induced during blood collection by prior femoral venipuncture. To our knowledge, this report is the first description of an arteriovenous fistula in a prosimian. Successful surgical correction of suspected iatrogenic femoral arteriovenous fistulas in a cynomolgus monkey (Macaca fascicularis) and a rhesus macaque (Macaca mulatta) have been reported previously. Arteriovenous fistula formation should be considered as a rare potential complication of venipuncture and as a treatable cause of congestive heart failure in lemurs.

  7. Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.

    Science.gov (United States)

    Daniel, M D; Letvin, N L; Sehgal, P K; Schmidt, D K; Silva, D P; Solomon, K R; Hodi, F S; Ringler, D J; Hunt, R D; King, N W

    1988-04-15

    The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme-linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero-positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease.

  8. Co-localization of histamine and norepinephrine in sympathetic ganglia and exocytosis of endogenous histamine from cardiac sympathetic nerve endings of macaca mulatto monkey

    Institute of Scientific and Technical Information of China (English)

    Ming-kaiLI; Xiao-xingLUO; Liang-weiCHEN; ZhongCHEN; JiaMENG; JingHU; Yu-meiWU; Jing-ruMENG; ZhengHOU; XueMA

    2005-01-01

    AIM To provide the evidence about localization, biosynthesis, metabolism and release of histamine from the cardiac sympathetic nerve terminals, and endogenous sympathetic histamine could inhibit itsel frelease from the nerve terminal through the presynaptic histamine H3 receptor. METHODS Using double-labeled immunohistochemistry to observe the co-localization of histamine and NE in the superior cer-vical ganglia (SCG) of macaca mulatto monkey; Different-speed centrifugation to obtain the cardiac sympathetic nerve terminal model (the cardiac synaptosomes), spectrofluorometer and ELISA techniques to detect the release of histamine from the cardiacsynaptosomes. RESULTS ( 1 ) The coexistence of histamine and norepinephrine immunoreactivities was identified in the same neuron within SCG of macaca mulatto monkey. (2) Depolarization of macaca mulatto monkey cardiac synaptosomes with 50 mmol/L potassium caused the release of endogenous histamine,

  9. Efficacy of antibiotic-impregnated polymethylmethacrylate beads in a rhesus macaque (Macaca mulatta) with osteomyelitis.

    Science.gov (United States)

    Kelly, Kristi R; Kapatkin, Amy R; Zwingenberger, Allison L; Christe, Kari L

    2012-08-01

    Here we describe the successful surgical implementation of antibiotic-impregnated polymethylmethacrylate beads in a rhesus macaque (Macaca mulatta) with marked osteomyelitis. The macaque presented to the veterinary clinic with grossly contaminated bite wounds in the left ankle secondary to conspecific trauma. Radiographic findings were highly suggestive of osteomyelitis. Additional differential diagnoses included bony infarct, fracture, and cellulitis. In light of the location of the lesion and extensive tissue trauma, the animal had a poor prognosis. Systemic, broad-spectrum antibiotics were instituted. After 2 wk of care, lesions did not respond to empirical therapies. On consultation, a veterinary orthopedic surgeon at another facility recommended placement of antibiotic-impregnated polymethylmethacrylate beads at the sites of osteomyelitis. The animal underwent minor surgery in which beads were introduced into the wound. The monkey had a positive response to therapy. The animal regained full function and was returned to outdoor social housing. Veterinarians are encouraged to consider using antibiotic-impregnated polymethylmethacrylate beads when treating osteomyelitis in other nonhuman primates and in other traditional laboratory animal species.

  10. Troop Takeover and Reproductive Success of Wild Male Japanese Macaques on Yakushima Island (Macaca fuscata yakui

    Directory of Open Access Journals (Sweden)

    Sachiko Hayakawa

    2011-01-01

    Full Text Available Troop takeover is common in one-male primate groups, but there are few reports in multimale groups. Japanese macaques (Macaca fuscata form multimale groups and males commonly join troops at the bottom rank. On Yakushima island, however, where group size is relatively small, entrance into groups at the alpha position is also observed. This paper reports on the general features of troop takeover, on the predictors of takeover events, and on the reproductive success of takeover males. Troop takeovers occurred only in the mating season; nontroop males (NTMs did not cooperate with each other; former alpha males were rarely expelled from the troop; new alpha males did not commit infanticide; new alpha male tenure in the group was usually less than two years. Logistic regression analysis showed that the number of NTMs associating with a troop predicted the occurrence of troop takeover. Paternity discrimination revealed that 33.3% (3/9 of takeover males succeeded in siring offspring. Contrary to this low success rate, binary logistic regression analysis revealed that the takeover males can expect higher reproductive success compared to troop males. Entering a troop and out-competing the alpha male is one of many available strategies to attain reproductive success in male Japanese macaques.

  11. Male mate choice in Tibetan macaques Macaca thibetana at Mt. Huangshan, China

    Directory of Open Access Journals (Sweden)

    Min ZHANG, Jinhua LI, Yong ZHU, Xi WANG, Su WANG

    2010-04-01

    Full Text Available Though females are generally more selective in mate choice, males may also benefit from mate choice if male reproductive success is limited by factors other than simply the number of female mates, and if females differ in short-term reproductive potential. We studied male mate choice in a free-ranging troop of Tibetan macaques Macaca thibetana at Mt. Huangshan, China, from August 2007 to April 2008. We employed focal animal sampling and all occurrence sampling to record sexual related behaviors. Eight adult females were divided into three female quality categories according to the females’ age, rank and parity. Using male mating effort as a proxy for male mate choice, we found that males do distinguish female quality and show time-variant mating strategies. Specifically, females with dominant rank, high fecundity, and middle age attracted significantly more males. Our results suggest that female short-term reproductive potential appears to be an important variable in determining male mating effort. Male Tibetan macaques do exercise mate choice for higher quality females as well as reduce useless reproductive cost, which is consistent with the direct benefits theory of mate choice [Current Zoology 56 (2: 213–221, 2010].

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

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    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.

  13. Training pair-housed Rhesus macaques (Macaca mulatta) using a combination of negative and positive reinforcement.

    Science.gov (United States)

    Wergård, Eva-Marie; Temrin, Hans; Forkman, Björn; Spångberg, Mats; Fredlund, Hélène; Westlund, Karolina

    2015-04-01

    When training animals, time is sometimes a limiting factor hampering the use of positive reinforcement training (PRT) exclusively. The aim of this study was to evaluate the effects of a combination of negative and positive reinforcement training (NPRT). Twenty naïve female Rhesus macaques (Macaca mulatta) were trained in 30 sessions with either PRT (n=8) or NPRT (n=12) to respond to a signal, move into a selected cage section and accept confinement. In the NPRT-group a signal preceded the presentation of one or several novel, and thus aversive, stimuli. When the correct behaviour was performed, the novel stimulus was removed and treats were given. As the animal learned to perform the correct behaviour, the use of novel stimuli was decreased and finally phased out completely. None of the PRT-trained animals finished the task. Ten out of 12 monkeys in the NPRT-group succeeded to perform the task within the 30 training sessions, a significant difference from the PRT-group (p=0.0007). A modified approach test showed no significant difference between the groups (p=0.67) in how they reacted to the trainer. The results from this study suggest that carefully conducted NPRT can be an alternative training method to consider, especially when under a time constraint.

  14. Facial width-to-height ratio relates to dominance style in the genus Macaca

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    Marta Borgi

    2016-03-01

    Full Text Available Background. Physical, visual, chemical, and auditory cues signalling fighting ability have independently evolved in many animal taxa as a means to resolve conflicts without escalating to physical aggression. Facial width-to-height ratio (fWHR, i.e., the relative width to height of the face has been associated with dominance-related phenotypes both in humans and in other primates. In humans, faces with a larger fWHR are perceived as more aggressive. Methods. We examined fWHR variation among 11 species of the genus Macaca. Macaques have been grouped into four distinct categories, from despotic to tolerant, based on their female dominance style. Female dominance style is related to intra- and inter-sexual competition in both males and females and is the result of different evolutionary pressure across species. We used female dominance style as a proxy of intra-/inter-sexual competition to test the occurrence of correlated evolution between competitive regimes and dominance-related phenotypes. fWHR was calculated from 145 2D photographs of male and female adult macaques. Results. We found no phylogenetic signal on the differences in fWHR across species in the two sexes. However, fWHR was greater, in females and males, in species characterised by despotic female dominance style than in tolerant species. Discussion. Our results suggest that dominance-related phenotypes are related to differences in competitive regimes and intensity of inter- and intra-sexual selection across species.

  15. Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Dettmer, Amanda M; Ruggiero, Angela M; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2008-05-01

    A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates.

  16. Toxic shock due to Streptococcus pyogenes in a rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    García, Anapatricia; Paul, Katherine; Beall, Bernard; McClure, Harold

    2006-09-01

    Recent years have seen a worldwide resurgence in serious infections caused by group A streptococci. This group includes Streptococcus pyogenes, one of the most common pathogens among children which causes diverse suppurative infections, such as pharyngitis, as well as nonsuppurative infections with sequelae, such as rheumatoid fever and rheumatic heart disease. S. pyogenes produces several superantigen-like erythrogenic toxins, which are believed to be associated with pyrogenicity, erythromatous skin reactions, and various immunologic and cytotoxic effects. These toxins also can cause myocardial necrosis. In addition, recently reported streptococcal infections in obstetric human patients appear to be clinically different from classic puerperal sepsis. Here, we report a case of spontaneous streptococcal infection in a pregnant female rhesus monkey (Macaca mulatta). In addition to lesions consistent with bacteremia and toxic shock, this animal had severe cardiac lesions resembling those described in humans with rheumatic heart disease. S. pyogenes was isolated from intracardiac blood, liver, placenta, and fetal tissues. This isolate also had a unique M protein gene.

  17. Exploring the components, asymmetry and distribution of relationship quality in wild Barbary macaques (Macaca sylvanus.

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    Richard McFarland

    Full Text Available Social relationships between group members are a key feature of many animal societies. The quality of social relationships has been described by three main components: value, compatibility and security, based on the benefits, tenure and stability of social exchanges. We aimed to analyse whether this three component structure could be used to describe the quality of social relationships in wild Barbary macaques (Macaca sylvanus. Moreover, we examined whether relationship quality was affected by the sex, age and rank differences between social partners, and investigated the asymmetric nature of social relationships. We collected over 1,900 hours of focal data on seven behavioural variables measuring relationship quality, and used principal component analysis to investigate how these variables clustered together. We found that relationship quality in wild Barbary macaques can be described by a three component structure that represents the value, compatibility and security of a relationship. Female-female dyads had more valuable relationships and same-age dyads more compatible relationships than any other dyad. Rank difference had no effect on the quality of a social relationship. Finally, we found a high degree of asymmetry in how members of a dyad exchange social behaviour. We argue that the asymmetry of social relationships should be taken into account when exploring the pattern and function of social behaviour in animal societies.

  18. Diet of the Assamese macaque Macaca assamensis in lime-stone habitats of Nonggang, China

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    Qihai ZHOU, Hua WEI, Zhonghao HUANG, Chengming HUANG

    2011-02-01

    Full Text Available To enhance our understanding of dietary adaptations in macaques we studied the diet of the Assamese macaque Macaca assamensis in limestone seasonal rain forests at Nonggang Nature Reserve, China from September 2005 to August 2006. Our results show that although macaques fed on many plant species, 85.2% of the diet came from only 12 species, of which a bamboo species, Indocalamus calcicolus contributed to 62% of the diet. Young leaves were staple food items (74.1% of the diet for Assamese macaques at Nonggang, and constituted the bulk of monthly diets almost year-round, ranging from 44.9% (July to 92.9% (May. Young parts of Indocalamus calcicolus unexpanded leaves contributed to a large proportion of the young leaf diet in most months. Fruit accounted for only 17.4% of the diet, with a peak of consumption in July. We suggest that this highly folivorous diet may be related to the long lean season of fruit availability in limestone habitats as well as the utilization of cliffs of low fruit availability [Current Zoology 57 (1: 18–25, 2011].

  19. Body signals during social play in free-ranging rhesus macaques (Macaca mulatta): A systematic analysis.

    Science.gov (United States)

    Yanagi, Akie; Berman, Carol M

    2014-02-01

    Social play involves one of the most sophisticated types of communication, that is, the use of play signals. Most primate research on play signals has focused on the use of the play face. However, some species appear to exhibit a variety of play signals. For example, rhesus monkeys (Macaca mulatta) have been reported to use body movements or postures that might have signal value during social play, in addition to the play face. However, it is not clear whether these body signals actually meet several criteria necessary to label them as "play signals." Here we examine the forms and possible functions of seven candidate signals that we observed exclusively during social play contexts among free-ranging rhesus monkeys on Cayo Santiago. We aim to (1) distinguish them from actual play behavior (play involving contact or chasing) using loglinear analysis and (2) determine whether they predict playful behavior using modified PC-MC methods. Two candidate signals did not resemble any behaviors used in actual play. The other five signals contained elements that lasted longer or increased their conspicuousness over similar play behaviors, suggesting ritualized characteristics. Youngsters were likely to initiate contact or chasing play significantly sooner after candidate signals than in their absence. Thus, these candidate signals appear to meet critical criteria of signals that promote, moderate or facilitate play. As such, these findings open the door to questions about why multiple play signals have evolved. © 2013 Wiley Periodicals, Inc.

  20. A non-invasive study of alopecia in Japanese macaques Macaca fuscata

    Institute of Scientific and Technical Information of China (English)

    Peng ZHANG

    2011-01-01

    This article provides information on the phenomenon of alopecia in Japanese macaques, Macaca fuscata, in various environments and proposes a 3-step scoring system for a quantitative assessment of hair loss. Results suggest that alopecia is commonly observed in Japanese macaques, with 20.5% of individuals showing head alopecia and 4.7% showing back alopecia across eight study groups. Alopecia was more commonly observed in adult females (30.8% individuals showing head alopecia and 15.3% showing back alopecia) than in other age-sex classes. Seasonal variation of back alopecia was noted, in particular, individuals with patchy back hair were more frequently observed in winter than in summer. Seasonal variation was not observed in head hair. The distribution of alopecia was also different among study groups. The wild population generally had better hair condition than provisioned populations and captive populations. The present study used a non-invasive alopecia scoring system which can be a useful, rapid and non-invasive tool to monitor animal health and well-being at a population level.

  1. Positive reinforcement training as enrichment for singly housed rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Baker, K C; Bloomsmith, M A; Neu, K; Griffis, C; Maloney, M

    2010-08-01

    Positive reinforcement training is one component of behavioural management employed to improve psychological well-being. There has been regulatory promotion to compensate for restricted social housing in part by providing human interaction to singly caged primates, implying an efficacy standard for evaluating human interaction. The effect of positive reinforcement training on the behaviour of 61 singly housed laboratory rhesus macaques (Macaca mulatta) was evaluated at two large primate facilities. Training involved body part presentation and basic control behaviours. Baseline data were compared to two treatment phases presented in varying order across individuals, six minutes per week of positive reinforcement training and six minutes per week of unstructured human interaction. While a MANOVA involving behavioural categories and study conditions across study subjects was significant, univariate ANOVAs found no effect of phase within any behavioural category. Categorising subjects according to rearing, housing facility, or baseline levels of abnormal behaviour did not reveal changes in behaviour with positive reinforcement training or human interaction. This study failed to detect, to any degree, the types of behavioural changes documented in the scientific literature to result from pairing singly housed monkeys. Implementing short durations of positive reinforcement training across large numbers of singly housed animals may not be the most effective manner for incorporating positive reinforcement training in the behavioural management of laboratory macaques. Rather, directing efforts toward individuals with specific behavioural, management, clinical, research or therapeutic needs may represent a more fruitful approach to improving psychological well-being with this technique.

  2. Buton macaques (Macaca ochreata brunnescens): crops, conflict, and behavior on farms.

    Science.gov (United States)

    Priston, Nancy E C; Wyper, Rebecca M; Lee, Phyllis C

    2012-01-01

    One consequence of anthropogenic habitat alteration is that many nonhuman primates are forced into conflict interactions with humans and their livelihood activities, especially through crop raiding. These problems are particularly acute for the endemic and threatened Buton Island macaque (Macaca ochreata brunnescens), in southeast Sulawesi, Indonesia. Our study investigated the crop raiding behavior of this species over time. Foods eaten and the behavioral repertoire exhibited by macaques during crop raiding at and inside farm perimeters were observed over a period of 8 years (2002-2009). Storage organ crops (e.g. sweet potato) were abundant and most frequently raided by macaques. Individual macaques were most commonly observed to raid close (0-10 m) to farm perimeters. Activities such as feeding, resting, moving, and social interaction varied significantly as a function of penetration distance into the farm, but only marginally between age-sex classes. The annual average raid frequency per farm decreased over the latter years of the study period, raising questions about changes in macaque foraging and ranging behavior over time and their response to farm management and mitigation strategies.

  3. Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation.

    Science.gov (United States)

    Ueno, Masataka; Nakamichi, Masayuki

    2016-08-01

    It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation.

  4. Alterations in the upper facial growth of Macaca mulatta resulting from high-pull headgear.

    Science.gov (United States)

    Meldrum, R J

    1975-04-01

    Four prepubertal Macaca mulatta monkeys, ranging in age from 13 to 24 months, were used in an investigation of the effects of high-pull headgear (to a face-bow) therapy on the growth of the upper facial skeleton. Amalgam bone implants were placed across the frontomaxillary, frontozygomatic, zygomaticomaxillary, and zygomaticotemporal sutures in each animal. Three of the monkeys wore appliances consisting of a maxillary dental spling, a face-bow, two coil springs, and an acrylic helmet. The fourth monkey (control) wore only a dental splint and a face-bow. A continuous high-pull headgear force of 300 grams per side was applied to the three monkeys for 81, 87 and 89 days, respectively, before death. Procion brilliant red 8-HBS vital stain was administered to all four animals at the start of and 3 days before the end of the treatment period. The facial growth patterns were determined from lateral cephalograms taken before and after treatment, from direct measurement of implant separation at the sutures, and from histologic sections of the four mentioned facial sutures.

  5. Role of vocal tract characteristics in individual discrimination by Japanese macaques (Macaca fuscata)

    Science.gov (United States)

    Furuyama, Takafumi; Kobayasi, Kohta I.; Riquimaroux, Hiroshi

    2016-01-01

    The Japanese macaque (Macaca fuscata) exhibits a species-specific communication sound called the “coo call” to locate group members and maintain within-group contact. Monkeys have been demonstrated to be capable of discriminating between individuals based only on their voices, but there is still debate regarding how the fundamental frequencies (F0) and filter properties of the vocal tract characteristics (VTC) contribute to individual discrimination in nonhuman primates. This study was performed to investigate the acoustic keys used by Japanese macaques in individual discrimination. Two animals were trained with standard Go/NoGo operant conditioning to distinguish the coo calls of two unfamiliar monkeys. The subjects were required to continue depressing a lever until the stimulus changed from one monkey to the other. The test stimuli were synthesized by combining the F0s and VTC from each individual. Both subjects released the lever when the VTC changed, whereas they did not when the F0 changed. The reaction times to the test stimuli were not significantly different from that to the training stimuli that shared the same VTC. Our data suggest that vocal tract characteristics are important for the identification of individuals by Japanese macaques. PMID:27550840

  6. Thromboelastography values from pigtail macaques ( Macaca nemestrina): effects of age and sex.

    Science.gov (United States)

    Fong, Derek L; Ha, James C; Hotchkiss, Charlotte E

    2012-01-01

    Thromboelastography is a clinical laboratory test used to assess global hemostasis. With technologic advances and the test's reemergence in human medicine, its utility in veterinary medicine is being explored. Because assays for PT, aPTT, and d-dimers require platelet-poor plasma, whereas thromboelastography is performed on whole blood, thromboelastography provides a more accurate representation of coagulation and allows the identification of hypocoagulable, hypercoagulable, and hyperfibrinolytic states. Conflicting information has been reported about the effects of age and sex on thromboelastog- raphy in humans and animals. Human studies have reported significant effects of age and sex on thromboelastography more often than have animal studies, but few publications are available about thromboelastography in the nonhuman primate and laboratory animal literature. We used a sample of 50 pigtail macaques (Macaca nemestrina) to determine whether age or sex influence thromboelastography values. Of 5 measured and 2 calculated variables produced by thromboelastography, sex had a significant effect only on the lysis-30 parameter, which also showed significant interaction between age and sex; values increased with age in male macaques but decreased with age in female macaques. In addition, we used the data to define reference intervals for thromboelastography parameters in pigtail macaques.

  7. Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.

    Science.gov (United States)

    Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

    2010-12-15

    Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning.

  8. Impact of intravenous infusion time on AAV8 vector pharmacokinetics, safety, and liver transduction in cynomolgus macaques

    Directory of Open Access Journals (Sweden)

    Jenny A Greig

    2016-01-01

    Full Text Available Systemically delivered adeno-associated viral (AAV vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system. The dose of AAV8 vector in terms of genome copies per kilogram body weight and its concentration were fixed, while the rate of infusion varied to deliver the entire dose over different time periods, including 1, 10, or 90 minutes. Analyses during the in-life phase of the experiment included sequential evaluation of whole blood for vector genomes and appearance of proinflammatory cytokines. Liver tissues were analyzed at the time of necropsy for enhanced green fluorescent protein (eGFP expression and vector genomes. The data were remarkable with a relative absence of any statistically significant effect of infusion time on vector transduction, safety, and clearance. However, some interesting and unexpected trends did emerge.

  9. Widespread gene transfer in the central nervous system of cynomolgus macaques following delivery of AAV9 into the cisterna magna

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    Christian Hinderer

    2014-01-01

    Full Text Available Adeno-associated virus serotype 9 (AAV9 vectors have recently been shown to transduce cells throughout the central nervous system of nonhuman primates when injected into the cerebrospinal fluid (CSF, a finding which could lead to a minimally invasive approach to treat genetic and acquired diseases affecting the entire CNS. We characterized the transduction efficiency of two routes of vector administration into the CSF of cynomolgus macaques—lumbar puncture, which is typically used in clinical practice, and suboccipital puncture, which is more commonly used in veterinary medicine. We found that delivery of vector into the cisterna magna via suboccipital puncture is up to 100-fold more efficient for achieving gene transfer to the brain. In addition, we evaluated the inflammatory response to AAV9-mediated GFP expression in the nonhuman primate CNS. We found that while CSF lymphocyte counts increased following gene transfer, there were no clinical or histological signs of immune toxicity. Together these data indicate that delivery of AAV9 into the cisterna magna is an effective method for achieving gene transfer in the CNS, and suggest that adapting this uncommon injection method for human trials could vastly increase the efficiency of gene delivery.

  10. A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques.

    Science.gov (United States)

    Safronetz, David; Strong, James E; Feldmann, Friederike; Haddock, Elaine; Sogoba, Nafomon; Brining, Douglas; Geisbert, Thomas W; Scott, Dana P; Feldmann, Heinz

    2013-04-15

    The virulence of Soromba-R, a Lassa virus strain recently isolated from southern Mali, was assessed in 2 animal models of Lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. In both models, the Malian isolate demonstrated tissue tropism and viral titers similar to those of historical Lassa virus isolates from Sierra Leone (Josiah) and Liberia (Z-132); however, the Soromba-R isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanasia in macaques. Interestingly, in addition to the classic indicators of Lassa fever, Soromba-R infection presented with moderate to severe pulmonary manifestations in the macaque model. Analysis of host responses demonstrated increased immune activation in Soromba-R-infected macaques, particularly in neutrophil-activating or -potentiating proinflammatory cytokines or growth factors, including tumor necrosis factor α, macrophage inflammatory protein 1α, interleukin 1β, and granulocyte colony-stimulating factor, as well as interleukin 5, which may be responsible for the decreased lethality and uncharacteristic clinical presentation. These results suggest that the strain of Lassa virus circulating in Mali might be less pathogenic than strains circulating in the historical region of endemicity and may result in an atypical presentation for Lassa fever, which could complicate clinical diagnosis.

  11. Lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge.

    Science.gov (United States)

    Hutt, Julie A; Lovchik, Julie A; Drysdale, Melissa; Sherwood, Robert L; Brasel, Trevor; Lipscomb, Mary F; Lyons, C Rick

    2014-12-01

    Inhalational anthrax is caused by inhalation of Bacillus anthracis spores. The ability of B. anthracis to cause anthrax is attributed to the plasmid-encoded A/B-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. To better understand the contribution of these toxins to the disease pathophysiology in vivo, we used B. anthracis Ames strain and isogenic toxin deletion mutants derived from the Ames strain to examine the role of lethal toxin and edema toxin after pulmonary spore challenge of cynomolgus macaques. Lethal toxin, but not edema toxin, was required to induce sustained bacteremia and death after pulmonary challenge with spores delivered via bronchoscopy. After intravenous challenge with bacilli to model the systemic phase of infection, lethal toxin contributed to bacterial proliferation and subsequent host death to a greater extent than edema toxin. Deletion of protective antigen resulted in greater loss of virulence after intravenous challenge with bacilli than deletion of lethal toxin or edema toxin alone. These findings are consistent with the ability of anti-protective antigen antibodies to prevent anthrax and suggest that lethal factor is the dominant toxin that contributes to the escape of significant numbers of bacilli from the thoracic cavity to cause anthrax after inhalation challenge with spores.

  12. A New Phenylpyrazoleanilide, Y-320, Inhibits Interleukin 17 Production and Ameliorates Collagen-Induced Arthritis in Mice and Cynomolgus Monkeys

    Directory of Open Access Journals (Sweden)

    Hiroyuki Ushio

    2013-12-01

    Full Text Available Interleukin (IL-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC50 values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-α monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA.

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

    Science.gov (United States)

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

    2011-01-01

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

  14. Effects of ICOS+ T cell depletion via afucosylated monoclonal antibody MEDI-570 on pregnant cynomolgus monkeys and the developing offspring.

    Science.gov (United States)

    Nicholson, Simone M; Carlesso, Gianluca; Cheng, Lily I; Cook, Halie; DaCosta, Karma; Leininger, Joel; McKeever, Kathleen; Scott, Stephen Weasel; Taylor, Devon; Streicher, Katie; Eck, Steve; Reed, Molly; Faggioni, Raffaella; Herbst, Ronald; Dixit, Rakesh; Ryan, Patricia C

    2017-09-13

    MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (TFH) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did not cause any abortifacient effects. Changes in hematology and peripheral blood T lymphocyte subsets in maternal animals and infants and the attenuated infant IgG immune response to keyhole limpet hemocyanin (KLH) were attributed to MEDI-570 pharmacology. Adverse findings included aggressive fibromatosis in one dam and two infant losses in the high dose group with anatomic pathology findings suggestive of atypical lymphoid hyperplasia. The margin of safety relative to the no observed adverse effect level (NOAEL) for the highest planned clinical dose in the Phase 1a study was 7. This study suggests that women of child bearing potential employ effective methods of contraception while being treated with MEDI-570. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques.

    Science.gov (United States)

    Ellis, Amy; Balgeman, Alexis; Rodgers, Mark; Updike, Cassaundra; Tomko, Jaime; Maiello, Pauline; Scanga, Charles A; O'Connor, Shelby L

    2017-04-01

    Nonhuman primates can be used to study host immune responses to Mycobacterium tuberculosis Mauritian cynomolgus macaques (MCMs) are a unique group of animals that have limited major histocompatibility complex (MHC) genetic diversity, such that MHC-identical animals can be infected with M. tuberculosis Two MCMs homozygous for the relatively common M1 MHC haplotype were bronchoscopically infected with 41 CFU of the M. tuberculosis Erdman strain. Four other MCMs, which had at least one copy of the M1 MHC haplotype, were infected with a lower dose of 3 CFU M. tuberculosis All animals mounted similar T-cell responses to CFP-10 and ESAT-6. Two epitopes in CFP-10 were characterized, and the MHC class II alleles restricting them were determined. A third epitope in CFP-10 was identified but exhibited promiscuous restriction. The CFP-10 and ESAT-6 antigenic regions targeted by T cells in MCMs were comparable to those seen in cases of human M. tuberculosis infection. Our data lay the foundation for generating tetrameric molecules to study epitope-specific CD4 T cells in M. tuberculosis-infected MCMs, which may guide future testing of tuberculosis vaccines in nonhuman primates. Copyright © 2017 American Society for Microbiology.

  16. Individual differences in the effects of environmental stimuli on cocaine choice in socially housed male cynomolgus monkeys.

    Science.gov (United States)

    Czoty, Paul W; Nader, Michael A

    2012-11-01

    Studies in laboratory animals have demonstrated an influence of environmentally derived stress and enrichment on the reinforcing effects of stimulants. To characterize the effects of acute exposure to ethologically valid environmental stimuli on the reinforcing strength of cocaine relative to food in socially housed monkeys. Choice between cocaine and food was assessed in subsets of 16 socially housed (4/pen) male cynomolgus monkeys immediately after the following manipulations: (1) treats placed in home cage, (2) a 10-min exposure to a rubber snake, or (3) 3 to 7 days of living in a larger environment without cage mates. Placing treats in the home cage shifted the cocaine dose-response curve to the left in five monkeys tested and to the right in 4 of 12 animals. The rubber snake significantly shifted the cocaine choice curve to the left in dominant monkeys. Exposure to an enlarged environment decreased cocaine choice in 9 of 15 monkeys; this effect was transient and not related to social rank. Repeated testing did not affect cocaine choice. Brief exposure to environmental events hypothesized to be stressors or enrichment altered cocaine choice, although not all individuals were affected and the effects were transient. Importantly, the data suggest that implementing positive changes in the environment produced effects that are clinically desirable. Understanding the behavioral and neurobiological mechanisms mediating sensitivity to environmental events in socially housed animals will lead to better treatment strategies for drug addiction.

  17. Preparation of highly specific radioactivity [{sup 18}F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ryzhikov, Nikolaj N. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Seneca, Nicholas [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD 20892 (United States); Krasikova, Raisa N. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Gomzina, Natalia A. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Shchukin, Evgeny [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Fedorova, Olga S. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Vassiliev, Dmitrij A. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Gulyas, Balazs [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Hall, Hakan [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Savic, Ivanka [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Halldin, Christer [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)]. E-mail: christer.halldin@cns.ki.se

    2005-02-01

    A straightforward method for the preparation of no-carrier-added (n.c.a.) [{sup 18}F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K{sup 18}F/kryptofix complex in DMF at 160 deg. C for 30 min and equimolar ratio [K/K2.2.2]{sup +18}F{sup -}/precursor. Under these conditions, an {sup 18}F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [{sup 18}F]flumazenil as for [{sup 11}C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [{sup 18}F]Flumazenil is a suitable radioligand for PET assessment of the BZR.

  18. Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys.

    Science.gov (United States)

    Czoty, Paul W; Nader, Michael A

    2015-03-13

    Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

  19. Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques.

    Science.gov (United States)

    Warren, Travis K; Whitehouse, Chris A; Wells, Jay; Welch, Lisa; Charleston, Jay S; Heald, Alison; Nichols, Donald K; Mattix, Marc E; Palacios, Gustavo; Kugleman, Jeffrey R; Iversen, Patrick L; Bavari, Sina

    2016-02-01

    Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.

  20. Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques.

    Directory of Open Access Journals (Sweden)

    Travis K Warren

    2016-02-01

    Full Text Available Marburg virus (MARV is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6 of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI. The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.

  1. A 52-week safety study in cynomolgus macaques for genetically modified rice expressing Cry1Ab/1Ac protein.

    Science.gov (United States)

    Mao, Jie; Sun, Xing; Cheng, Jian-Hua; Shi, Yong-Jie; Wang, Xin-Zheng; Qin, Jun-Jie; Sang, Zhi-Hong; He, Kun; Xia, Qing

    2016-09-01

    A 52-week feeding study in cynomolgus macaques was carried out to evaluate the safety of Bt rice Huahui 1 (HH1), a transgenic rice line expressing Cry1Ab/1Ac protein. Monkeys were fed a diet with 20% or 60% HH1 rice, 20% or 60% parental rice (Minghui 63, MH63), normal diet, normal diet spiked with purified recombinant Cry1Ab/1Ac fusion protein or bovine serum albumin (BSA) respectively. During the feeding trail, clinical observations were conducted daily, and multiple parameters, including body weight, body temperature, electrocardiogram, hematology, blood biochemistry, serum metabolome and gut microbiome were examined at regular intervals. Upon sacrifice, the organs were weighted, and the macroscopic, microscopic and electron microscopic examinations were performed. The results show no adverse or toxic effects of Bt rice HH1 or Cry1Ab/1Ac fusion protein on monkeys. Therefore, the present 52-week primate feeding study suggests that the transgenic rice containing Cry 1Ab/1Ac is equivalent to its parental rice line MH63.

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

    Directory of Open Access Journals (Sweden)

    Alfonso Galván-Montaño

    2010-06-01

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

  3. Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

    Science.gov (United States)

    Wade, C. E.; Ortiz, R. M.

    1997-01-01

    Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

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

    Directory of Open Access Journals (Sweden)

    Ines Fürtbauer

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

  5. Microvasculature of the Olfactory Organ in the Japanese Monkey (Macaca fuscata fuscata)

    Science.gov (United States)

    Okada, Shigenori; Schraufnagel, Dean E.

    2002-06-01

    Olfaction is an important and primitive sense. As its importance has changed with evolution, anatomic adjustments have occurred in its structure and vasculature. Primates are a family of vertebrates that have had to develop their visual system to adapt to the arboreal environment and have evolved from a macrosmatic to a microsmatic species as the optic system has enlarged. This has resulted in anatomic changes of a small but critical area at the base of the brain. This paper describes the three-dimensional vascular anatomy of the olfactory organ of the Japanese monkey (Macaca fuscata fuscata). This is best understood by dividing the organ into three parts: the olfactory tract, olfactory bulb, and olfactory nerves in the nasal mucosa. The bulb can be partitioned into an outer or cortical part and inner or medullary part. The vasculature and tissue were examined grossly and with light microscopy and scanning electron microscopy of vascular corrosion casts. The olfactory tract and bulb were supplied by an arteriole from the anterior cerebral artery on each side. The tract was supplied by capillaries running spirally with a coarse network. At the olfactory bulb, the arteriole ramified into the intracortical and medullary branches that formed capillary networks. The bulbar intracortical capillaries were divided into two layers with different densities and vascular patterns. The capillaries of the superficial layer had a ladder-like pattern. The branches that ran into the medulla of the olfactory bulb were more widely spaced. Twigs from the posterior ethmoidal artery ran along the nerve fiber and formed intra- and extrafascicular networks. Each region of the olfactory organ had characteristic three-dimensional vascular patterns that were related to their cellular architecture.

  6. Whom to groom and for what? Patterns of grooming in female Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Roubová, Veronika; Konečná, Martina; Šmilauer, Petr; Wallner, Bernard

    2015-01-01

    Grooming is one of the most conspicuous social interactions among nonhuman primates. The selection of grooming partners can provide important clues about factors relevant for the distribution of grooming within a social group. We analyzed grooming behavior among 17 semi-free ranging female Barbary macaques (Macaca sylvanus). We tested whether grooming is related to kinship, rank and friendship. Furthermore, we tested whether grooming is reciprocated or exchanged for rank related benefits (i.e. lower aggression and increased tolerance whilst feeding). We found that in general grooming was reciprocally exchanged, directed up the hierarchy and at the same time affected by friendship and kinship. Grooming was more frequent among individuals with higher friendship values as well as amongst related individuals. We also divided our data set on the basis of rank difference and tested if different power asymmetries between individuals affected the tendency to exchange grooming for rank related benefits and grooming reciprocation. In support of our initial hypothesis our results show that the reciprocation of grooming was a significant predictor of grooming interactions between individuals of similar rank, but not between those individuals more distantly separated in the social hierarchy. However, we did not find any evidence for grooming being exchanged for rank related benefits in either data set. Our results, together with previously published studies, illustrate the behavioral flexibility of macaques. It is clear that multiple studies of the same species are necessary to gather the data required for the solid comparative studies needed to shed light on patterns of grooming behavior in primates.

  7. Feeding behavior and aggression in wild Siberut macaques (Macaca siberu) living under low predation risk.

    Science.gov (United States)

    Richter, Christin; Gras, Pierre; Hodges, Keith; Ostner, Julia; Schülke, Oliver

    2015-07-01

    Investigating which factors influence feeding competition is crucial for our understanding of the diversity of social relationships. Socio-ecological models differ in their predictions whether predation risk directly influences feeding competition and which factors exactly predict contest competition. We investigated feeding competition in Siberut macaques (Macaca siberu), a species endemic to Siberut Island (West Sumatra, Indonesia). Siberut macaques experience low predation risk, as major predators (felids, raptors) are absent. They are therefore appropriate subjects to test the prediction that low predation risk reduces feeding competition. To estimate contest potential, we quantified size, spatial distribution and density of food plants, and the availability of alternative resources. We recorded behavior in food patches using a modified focal tree method. Food patches, sorted by decreasing average feeding group size, included large trees (40% of focal plant observations), lianas/strangler (16%), medium trees (9%), small (palm) trees (20%), and rattan (15%). Most food patches were clumped but occurred at low densities relative to the area of average group spread. Thus, availability of alternative food patches was low. Although food patch characteristics indicate high contest potential, the observed aggression rate (0.13 bouts between adults/h) was low relative to other primates. Average feeding group size was small relative to total group size, and feeding group size matched crown volume. Perceived predation risk was low, based on spatial and feeding behavior of juveniles. Together, these results suggest that predation risk may influence feeding competition. Social and temporal factors (patch feeding time), but not ecological factors (fruit abundance in patch and forest, alternative resources) predicted aggression frequency in food patches. Overall, comparative data are still relatively scarce, and researchers should collect more data on group spread, sub

  8. Pyrosequencing as a method for SNP identification in the rhesus macaque (Macaca mulatta

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    Kanthaswamy S

    2008-05-01

    Full Text Available Abstract Background Rhesus macaques (Macaca mulatta are the primate most used for biomedical research, but phenotypic differences between Indian-origin and Chinese rhesus macaques have encouraged genetic methods for identifying genetic differences between these two populations. The completion of the rhesus genome has led to the identification of many single nucleotide polymorphisms (SNPs in this species. These single nucleotide polymorphisms have many advantages over the short tandem repeat (STR loci currently used to assay genetic variation. However, the number of currently identified polymorphisms is too small for whole genome analysis or studies of quantitative trait loci. To that end, we tested a combination of methods to identify large numbers of high-confidence SNPs, and screen those with high minor allele frequencies (MAF. Results By testing our previously reported single nucleotide polymorphisms, we identified a subset of high-confidence, high-MAF polymorphisms. Resequencing revealed a large number of regionally specific SNPs not identified through a single pyrosequencing run. By resequencing a pooled sample of four individuals, we reliably identified loci with a MAF of at least 12.5%. Finally, we found that when applied to a larger, geographically variable sample of rhesus, a large proportion of our loci were variable in both populations, and very few loci were ancestry informative. Despite this fact, the SNP loci were more effective at discriminating Indian and Chinese rhesus than STR loci. Conclusion Pyrosequencing and pooled resequencing are viable methods for the identification of high-MAF SNP loci in rhesus macaques. These SNP loci are appropriate for screening both the inter- and intra-population genetic variation.

  9. When dispersal fails: unexpected genetic separation in Gibraltar macaques (Macaca sylvanus).

    Science.gov (United States)

    Modolo, Lara; Martin, Robert D; van Schaik, Carel P; van Noordwijk, Maria A; Krũtzen, Michael

    2008-09-01

    Barbary macaques (Macaca sylvanus), now restricted in the wild to a few isolated forested areas of Morocco and Algeria, are present in a free-ranging colony on Gibraltar. For many decades, the Gibraltar colony was exposed to multiple bottlenecks due to highly nonrandom removal of animals, followed by repeated introductions of animals from North Africa. Moreover, because of complete isolation, Gibraltar's several social groups of macaques provide an ideal system to study the genetic consequences of dispersal in cercopithecines in situ. Predictions of genetic consequences due to male-biased dispersal in cercopithecines will be different for autosomal and maternally inherited genetic markers, such as the control region of the mitochondrial DNA. We used a panel of 14 highly polymorphic microsatellite loci and part of the hypervariable region I of the mitochondrial control region to estimate genetic structure between five social groups in Gibraltar. Surprisingly, for autosomal markers, both classical summary statistics and an individual-based method using a Bayesian framework detected significant genetic structure between social groups in Gibraltar, despite much closer proximity than wild Algerian and Moroccan populations. Mitochondrial data support this finding, as a very substantial portion of the total genetic variation (70.2%) was found between social groups. Using two Bayesian approaches, we likewise identified not only a small number of male first-generation immigrants (albeit less than expected for cercopithecines) but also unexpectedly a few females. We hypothesize that the culling of males that are more likely to disperse might slow down genetic homogenization among neighbouring groups, but may also and more perversely produce selection on certain behavioural traits. This may have important repercussions for conservation, as it could lead to evolutionary changes that are not due to inbreeding or genetic drift.

  10. Patterns of infant handling and relatedness in Barbary macaques (Macaca sylvanus) on Gibraltar.

    Science.gov (United States)

    Kümmerli, Rolf; Martin, Robert D

    2008-10-01

    Among papionin primates, the Barbary macaque (Macaca sylvanus) shows the most extensive interactions between infants and group members other than the mother. Two different types of interactions occur: (1) long-lasting dyadic interactions between a handler and an infant, and (2) brief triadic interactions between two handlers involving an infant. Previous investigations showed that infant handling by males is best explained as use of infants to manage relationships with other males. In contrast, no adaptive explanation for infant handling by females emerged. Here, we compared the infant-handling pattern between subadult/adult males and subadult/adult females in a free-ranging group of 46 Barbary macaques on Gibraltar to test whether the relationship management hypothesis also applies to female handlers. We further investigated the infant-handling pattern of juveniles and used microsatellite markers to estimate relatedness between infant handlers and the infant's mother. We found that males, females and juveniles all participated extensively in triadic interactions using infants of above-average related females. In contrast, only males and juveniles were highly involved in dyadic interactions with infants of related females, while females rarely handled infants other than their own. The pattern of infant handling was entirely compatible with the predictions of the relationship management hypothesis for males and mostly so for females. Moreover, our genetic analysis revealed that males and females differ in their partner choice: while females preferred to interact with related females, males had no significant preference to interact with related males. We further discuss the observed above-average relatedness values between infant handlers and the infant's mother in the light of kin-selection theory.

  11. Factors increasing snake detection and perceived threat in captive rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Etting, Stephanie F; Isbell, Lynne A; Grote, Mark N

    2014-02-01

    The primary predators of primates are all ambush hunters, and yet felids, raptors, and snakes differ in aspects of their ecology that affect the evasive strategies of their primate prey. Felids and raptors can traverse long distances quickly, thus the urgency of threat they present increases as they come closer in proximity to primates. In contrast, snakes do not move rapidly over long distances, and so primates may be reasonably safe even at close distances provided snakes can be detected and monitored. We investigated the ability of captive rhesus macaques (Macaca mulatta) to detect snakes at distances ranging from 15 to 1.5 m. We also examined variation in intensity of perceived threat by applying a Hidden Markov Model to infer changes in underlying state from observable behaviors, that is, increased attention and mobbing. We found that the macaques often failed to detect snake models but that closer proximity improved snake detection, which is necessary before threat can be perceived. We also found that having only one individual in fairly close proximity (≤ 7.5 m) was sufficient to alert the rest of the group and so the chances of detection did not increase with increasing group size. Finally, we found that when the snakes were perceived, they did not elicit greater intensity of response with closer proximity. These results provide evidence that the threat from snakes is greatest when they are in proximity to primates but are unseen. When snakes are seen, however, distance appears not to affect primates' perceived risk, in contrast to their perceived risk from raptors and felids.

  12. Auditory Rehabilitation in Rhesus Macaque Monkeys (Macaca mulatta) with Auditory Brainstem Implants

    Institute of Scientific and Technical Information of China (English)

    Zhen-Min Wang; Zhi-Jun Yang; Fu Zhao; Bo Wang; Xing-Chao Wang; Pei-Ran Qu; Pi-Nan Liu

    2015-01-01

    Background:The auditory brainstem implants (ABIs) have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients.The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device.This study aimed to establish an animal model of ABI in adult rhesus macaque monkey (Macaca mulatta).Methods:Six adult rhesus macaque monkeys (M.mulatta) were included.Under general anesthesia,a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid (RS) approach.The electrical auditory brainstem response (EABR) waves were tested to ensure the optimal implant site.After the operation,the EABR and computed tomography (CT) were used to test and verify the effectiveness via electrophysiology and anatomy,respectively.The subjects underwent behavioral observation for 6 months,and the postoperative EABR was tested every two weeks from the 1st month after implant surgery.Result:The implant surgery lasted an average of 5.2 h,and no monkey died or sacrificed.The averaged latencies of peaks Ⅰ,Ⅱ and Ⅳ were 1.27,2.34 and 3.98 ms,respectively in the ABR.One-peak EABR wave was elicited in the operation,and one-or two-peak waves were elicited during the postoperative period.The EABR wave latencies appeared to be constant under different stimulus intensities;however,the amplitudes increased as the stimulus increased within a certain scope.Conclusions:It is feasible and safe to implant ABIs in rhesus macaque monkeys (M.mulatta) through a modified suboccipital RS approach,and EABR and CT are valid tools for animal model establishment.In addition,this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.

  13. No-scalpel vasectomy by electrocauterization in free range rhesus macaques (Macaca mulatta

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    A. Raj

    2012-02-01

    Full Text Available The objective of the study was to standardize a new method of vasectomy in male rhesus macaques (Macaca mulatta. A total of 208 free range male rhesus macaques captured from different locations in Shivalik Hills in a population control programme of the rhesus macaques in India. General anaesthesia was achieved by using a combination of ketamine hydrochloride at 8 mg/kg body weight and xylazine hydrochloride at 2mg/kg body weight intramuscularly in squeeze cage. Surgical procedure of vasectomy was carried out by single-hole no-scalpel technique using a single pre-scrotal skin incision above the median raphae. Spermatic cord was grasped with ringed forceps and was pulled out through the single-hole incision. Vas deferens was separated from the artery-vein complexus and about 3-4 cm portion of vas deferens was resected. Cauterization of both ends of the vas deferens was achieved with electrocautery. The induction time for anaesthesia was 1.40±0.18 min while surgical time for vasectomy was found to be 5.09±0.22 min. Recovery from general anaesthesia was without side-effects after a mean duration of 36.07±1.22 min, whereas the duration of anaesthesia was observed to be 82.27±4.96 min. There were no major complications following the surgery and recovery of animals was smooth. Animals were kept in postoperative care for five days and released at the same capturing site.

  14. Diversity and molecular phylogeny of mitochondrial DNA of rhesus macaques (Macaca mulatta) in Bangladesh.

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    Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Kanthaswamy, Sree; Smith, David Glenn

    2014-11-01

    While studies of rhesus macaques (Macaca mulatta) in the eastern (e.g., China) and western (e.g., India) parts of their geographic range have revealed major genetic differences that warrant the recognition of two different subspecies, little is known about genetic characteristics of rhesus macaques in the transitional zone extending from eastern India and Bangladesh through the northern part of Indo-China, the probable original homeland of the species. We analyzed genetic variation of 762 base pairs of mitochondrial DNA from 86 fecal swab samples and 19 blood samples from 25 local populations of rhesus macaque in Bangladesh collected from January 2010 to August 2012. These sequences were compared with those of rhesus macaques from India, China, and Myanmar. Forty-six haplotypes defined by 200 (26%) polymorphic nucleotide sites were detected. Estimates of gene diversity, expected heterozygosity, and nucleotide diversity for the total population were 0.9599 ± 0.0097, 0.0193 ± 0.0582, and 0.0196 ± 0.0098, respectively. A mismatch distribution of paired nucleotide differences yielded a statistically significantly negative value of Tajima's D, reflecting a population that rapidly expanded after the terminal Pleistocene. Most haplotypes throughout regions of Bangladesh, including an isolated region in the southwestern area (Sundarbans), clustered with haplotypes assigned to the minor haplogroup Ind-2 from India reflecting an east to west dispersal of rhesus macaques to India. Haplotypes from the southeast region of Bangladesh formed a cluster with those from Myanmar, and represent the oldest rhesus macaque haplotypes of Bangladesh. These results are consistent with the hypothesis that rhesus macaques first entered Bangladesh from the southeast, probably from Indo-China, then dispersed westward throughout eastern and central India.

  15. Using biological markets principles to examine patterns of grooming exchange in Macaca thibetana.

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    Balasubramaniam, K N; Berman, C M; Ogawa, H; Li, J

    2011-12-01

    Biological markets principles offer testable hypotheses to explain variation in grooming exchange patterns among nonhuman primates. They predict that when within-group contest competition (WGC) is high and dominance hierarchies steep, grooming interchange with other "commodity" behaviors (such as agonistic support) should prevail. In contrast, when WGC is low and gradients shallow, market theory predicts that grooming reciprocity should prevail. We tested these predictions in a wild, provisioned Tibetan macaque (Macaca thibetana) group across six time periods during which the group had been subjected to varying degrees of range restriction. Data on female-female aggression, grooming, and support were collected using all-occurrences and focal animal sampling techniques, and analyzed using ANCOVA methods and correlation analyses. We found that hierarchical steepness varied significantly across periods, but did not correlate with two indirect indicators of WGC (group size and range restriction) in predicted directions. Contrary to expectations, we found a negative correlation between steepness and group size, perhaps because the responses of group members to external risks (i.e. prolonged and unavoidable exposure to humans) may have overshadowed the effects of WGC. As predicted, grooming reciprocity was significant in each period and negatively correlated with steepness, even after we controlled group size, kinship, rank differences, and proximity. In contrast, there was no evidence for grooming interchange with agonistic support or for a positive relationship between interchange and steepness. We hypothesize that stressful conditions and/or the presence of stable hierarchies during each period may have led to a greater market demand for grooming than support. We suggest that future studies testing these predictions consider more direct measures of WGC and commodities in addition to support, such as feeding tolerance and access to infants.

  16. Rhesus monkeys (Macaca mulatta detect rhythmic groups in music, but not the beat.

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    Henkjan Honing

    Full Text Available It was recently shown that rhythmic entrainment, long considered a human-specific mechanism, can be demonstrated in a selected group of bird species, and, somewhat surprisingly, not in more closely related species such as nonhuman primates. This observation supports the vocal learning hypothesis that suggests rhythmic entrainment to be a by-product of the vocal learning mechanisms that are shared by several bird and mammal species, including humans, but that are only weakly developed, or missing entirely, in nonhuman primates. To test this hypothesis we measured auditory event-related potentials (ERPs in two rhesus monkeys (Macaca mulatta, probing a well-documented component in humans, the mismatch negativity (MMN to study rhythmic expectation. We demonstrate for the first time in rhesus monkeys that, in response to infrequent deviants in pitch that were presented in a continuous sound stream using an oddball paradigm, a comparable ERP component can be detected with negative deflections in early latencies (Experiment 1. Subsequently we tested whether rhesus monkeys can detect gaps (omissions at random positions in the sound stream; Experiment 2 and, using more complex stimuli, also the beat (omissions at the first position of a musical unit, i.e. the 'downbeat'; Experiment 3. In contrast to what has been shown in human adults and newborns (using identical stimuli and experimental paradigm, the results suggest that rhesus monkeys are not able to detect the beat in music. These findings are in support of the hypothesis that beat induction (the cognitive mechanism that supports the perception of a regular pulse from a varying rhythm is species-specific and absent in nonhuman primates. In addition, the findings support the auditory timing dissociation hypothesis, with rhesus monkeys being sensitive to rhythmic grouping (detecting the start of a rhythmic group, but not to the induced beat (detecting a regularity from a varying rhythm.

  17. A behavioral taxonomy of loneliness in humans and rhesus monkeys (Macaca mulatta.

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    John P Capitanio

    Full Text Available Social relationships endow health and fitness benefits, but considerable variation exists in the extent to which individuals form and maintain salutary social relationships. The mental and physical health effects of social bonds are more strongly related to perceived isolation (loneliness than to objective social network characteristics. We sought to develop an animal model to facilitate the experimental analysis of the development of, and the behavioral and biological consequences of, loneliness. In Study 1, using a population-based sample of older adults, we examined how loneliness was influenced both by social network size and by the extent to which individuals believed that their daily social interactions reflected their own choice. Results revealed three distinct clusters of individuals: (i individuals with large networks who believed they had high choice were lowest in loneliness, (ii individuals with small social networks who believed they had low choice were highest in loneliness, and (iii the remaining two groups were intermediate and equivalent in loneliness. In Study 2, a similar three-group structure was identified in two separate samples of adult male rhesus monkeys (Macaca mulatta living in large social groups: (i those high in sociability who had complex social interaction with a broad range of social partners (putatively low in loneliness, (ii those low in sociability who showed tentative interactions with certain classes of social partners (putatively high in loneliness, and (iii those low in sociability who interacted overall at low levels with a broad range of social partners (putatively low or intermediate in loneliness. This taxonomy in monkeys was validated in subsequent experimental social probe studies. These results suggest that, in highly social nonhuman primate species, some animals may show a mismatch between social interest and social attainment that could serve as a useful animal model for experimental and

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

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

    2011-01-01

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

  19. Choriodecidual infection downregulates angiogenesis and morphogenesis pathways in fetal lungs from Macaca nemestrina.

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    Ryan M McAdams

    Full Text Available BACKGROUND: Intrauterine exposure to amniotic fluid (AF cytokines is thought to predispose to bronchopulmonary dysplasia (BPD. We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD. METHODS: Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term = 172 days received choriodecidual inoculation of either: 1 Group B Streptococcus (n = 5 or 2 saline (n = 5. Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry. RESULTS: Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening and one control (peri-mortem hemorrhage. Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6 were detected in GBS versus controls (p<0.05. Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05 with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development. CONCLUSIONS: A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in

  20. Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

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    Anson Donald S

    2011-09-01

    Full Text Available Abstract Background There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-γ ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl β-galactosidase assay with primary isolates of HIV-1. Results This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques

  1. Facial paralysis and lymphocytic facial neuritis in a rhesus macaque (Macaca mulatta) positive for simian retrovirus type D2.

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    Hampton, Anna L; Colby, Lesley A; Bergin, Ingrid L

    2011-12-01

    Simian retrovirus type D (SRVD) is a naturally occurring betaretrovirus in nonhuman primates of the genus Macaca. Infection can lead to a variety of clinical, hematologic, and histopathologic abnormalities. We report an unusual clinical presentation of facial paralysis and histologic lymphocytic neuritis in an SRVD type 2 (SRVD2)-infected rhesus macaque (Macaca mulatta) with a catheter-associated vena caval thrombus, anemia, thrombocytopenia, and multisystemic lymphoid hyperplasia. At initial presentation, a right atrial mass was detected by echocardiography. The macaque was clinically asymptomatic but had persistent anemia, thrombocytopenia, hyperglobulinemia, and later neutropenia. It was seropositive for SRV and PCR-positive for SRVD 2. Approximately 1 mo after initial presentation, the macaque developed right facial paralysis and was euthanized. Histologic lesions included lymphoplasmacytic aggregates affecting multiple organs, consistent with SRV-related lymphoid hyperplasia. The right facial nerve showed lymphoplasmacytic inflammation. The nerve itself was negative immunohistochemically for SRV antigen, but antigen was present infrequently in pericapillary lymphoid cells within the facial nerve and abundantly within lymphoid aggregates in the adjacent parotid salivary gland, bone marrow, and soft tissue. Known neurotropic viruses could not be identified. Given the widespread inflammation in this macaque, particularly in the area surrounding the facial nerve, lymphocytic neuritis and facial paralysis likely were an indirect effect of SRV infection due to local extension of SRV-related inflammation in the surrounding tissue.

  2. Passive antibody therapy of Lassa fever in cynomolgus monkeys: importance of neutralizing antibody and Lassa virus strain.

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    Jahrling, P B; Peters, C J

    1984-05-01

    Lassa virus-infected cynomolgus monkeys were passively immunized with immune plasma of primate or human origin to gain insight into criteria for plasma selection and administration to human Lassa fever patients. Protective efficacy was correlated with neutralizing antibody concentrations, expressed as a log10 neutralization index (LNI). Convalescent Lassa-immune monkey plasma was titrated for protective efficacy in monkeys by intravenous inoculation with dilutions of plasma on the day of subcutaneous Lassa virus inoculation (day 0) and again on days 3 and 6. Monkeys that received undiluted plasma (LNI = 4.1) (1 ml/kg per treatment) survived a lethal viral dose, whereas those given a 1:3 dilution (LNI = 2.6) of this same plasma (1 ml/kg per treatment) died. Protection was restored when the volume of the 1:3 plasma dilution was increased to 3 ml/kg per treatment. Plasma diluted 1:9 or more (LNI = 1.5 or less) delayed onset and suppressed the magnitude of viremia but failed to confer protection at 3 ml/kg per treatment. Immunological enhancement, defined as increased viremia or accelerated death, did not occur following inadequate treatment. Human convalescent plasma also protected recipient monkeys; reductions in mortality and viremia were accurately predicted by the LNI of the plasma. Plasma of Liberian origin neutralized a Liberian Lassa strain more effectively than a Sierra Leone strain in vitro (LNI = 2.8 and 1.6, respectively) and protected monkeys more effectively against the Liberian strain. Geographic origin is thus a factor in the selection of optimal plasma for treatment of human Lassa fever, since geographically matched plasma is more likely to contain adequate LNI titers against homologous Lassa virus strains.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Early potent protection against heterologous SIVsmE660 challenge following live attenuated SIV vaccination in Mauritian cynomolgus macaques.

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    Neil Berry

    Full Text Available BACKGROUND: Live attenuated simian immunodeficiency virus (SIV vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I/II haplotype or TRIM5α polymorphism and study outcome was identified. CONCLUSION/SIGNIFICANCE: This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system.

  4. Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

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    Glen eAcosta

    2012-01-01

    Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

  5. A novel fully human anti-CD40 monoclonal antibody, 4D11, for kidney transplantation in cynomolgus monkeys.

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    Imai, Atsushi; Suzuki, Tomomi; Sugitani, Atsushi; Itoh, Tomoo; Ueki, Shinya; Aoyagi, Takeshi; Yamashita, Kenichiro; Taniguchi, Masahiko; Takahashi, Nobuaki; Miura, Toru; Shimamura, Tsuyoshi; Furukawa, Hiroyuki; Todo, Satoru

    2007-10-27

    CD40-CD154 pathway blockade by anti-CD154 monoclonal antibodies (mAbs) significantly prolongs allograft survival in nonhuman primates. However, thromboembolic complications have prevented clinical application. Thus, blockade of the counter molecule by a novel fully human anti-CD40 mAb, 4D11, is an attractive alternative. Kidney transplantations were performed between outbred cynomolgus monkeys (stimulation index >3 in a mixed lymphocyte reaction). The animals were divided into five groups: nontreatment control (Group 1, n=3), 10-week treatment with either 10 mg/kg (Group 2, n=3), 20 mg/kg (Group 3, n=3), or 40 mg/kg (Group 4, n=1), and 4-week treatment (Group 5, n=1 each) with 10 mg/kg, 20 mg/kg, or 40 mg/kg followed by monthly administration. Graft survival, biochemistry, complete blood counts, lymphocyte phenotypes, blood drug levels, antidonor and antidrug antibodies, and renal histology were examined. Survival (days) was as follows: Group 1 (5, 6, 7), Group 2 (150, 108, 108), Group 3 (84, 108, 379), Group 4 (147), and Group 5 (147, 102, 112). Two animals in Group 3 with normal graft function were killed upon development of hydronephrosis and cerebral infarction. B lymphocytes fell to one-third of the preoperative value at 4 weeks after transplantation in all animals. Antidonor antibodies developed in most of the animals after stopping drug treatment or at the time of death. No animals except for one formed anti-4D11 antibody. 4D11 appears to be a promising agent for antirejection treatment in clinical organ transplantation.

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

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    Renato Sathler-Avelar

    2016-01-01

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

  7. Studies of tolerance induction through mixed chimerism in cynomolgus monkeys. Method for detection of chimeric cells and effect of thymic irradiation on induction of tolerance

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    Hoshino, Tomoaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    To establish the method for the detection of chimerism in cynomologus monkeys, we tested cross reactivity of various anti-HLA monoclonal antibodies (mAb) to cynomolgus monkeys. In 29 mAb we tested, only three monoclonal anti-HLA antibodies crossreacted with lymphocytes of monkeys. With these mAb, chimeric cell can be detected up to 1% by flow cytometric analysis (study 1). Utilizing the method we developed in study 1, we applied the regimen that induces mixed chimerism and skin graft tolerance in mice to renal allotransplantation of cynomolgus monkey. Regimen A includes non-lethal dose of total body irradiation (TBI), administration of anti-thymocyte globulin (ATG) for 3 days, donor bone marrow infusion and 45 days course of cyclosporine (CYA) administration. We added 7 Gy of thymic irradiation on day-6 in regimen B and on day-1 in regimen C. Although all monkeys in regimen A and B consistently developed chimerism, they rejected kidney allografts soon after stopping CYA. In contrast, 4 monkeys out of 5 failed to develop chimerism in regimen C, but renal allograft tolerance was induced in one monkey who developed chimerism in regimen C. In conclusion, the induction of chimerism is considered necessary but not sufficient for tolerance induction. (author)

  8. Establishment of heterotopic intestinal xenotransplantation model from pig to cynomolgus%猪到食蟹猴异位小肠移植模型的建立

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    姚丹华; 李幼生; 王剑; 毛琦; 郭明晓; 张少一; 孔文成; 任乐乐; 黎介寿

    2015-01-01

    Objective To investigate the procedures for establishing a stable model of intestinal xenotransplantation from pig to cynomolgus, with the purpose of providing a good experimental tool for the xenograft rejection study in intestinal xenotransplantation. Methods White wild-type pigs were used as donor and cynomolguses used as recipients. The procedure of segmental heterotopic intestinal xenotransplantation in recipients was performed as following: the donor`s anterior mesenteric artery was anastomosed end-to-side to the recipient`s infrarenal abdominal aorta, and the donor`s tributary of anterior mesenteric venous was anastomosed end-to-side to the recipient`s infrarenal inferior vena cave. Subsequently, both the proximal and distant ends of the graft intestine were stayed ligated. Results Segmental intestinal xenotransplantation was performed in 5 cynomolguses, with an average graft intestine length of (52.0 ± 5.7) cm. The success rate of vascular anastomosis was 100%, and the intestinal xenograft survival was 152±72(55~245) minutes. Conclusions A stable, repeatable model of segmental intestinal xenotransplantation from pig to cynomolgus was established, which would provide an ideal tool for further research on intestinal xenotransplantation from transgenic pig to cynomolgus.%目的:探讨稳定的猪到食蟹猴异位小肠移植模型建立方法,为异种小肠移植排斥反应的研究提供良好的实验工具。方法分别以白色杂种猪和食蟹猴做供、受体,采用供体小肠的肠系膜前动、静脉分别与受体肾下腹主动脉和肾下下腔静脉行端侧吻合,供体远、近端肠管结扎的方式建立异种节段性小肠移植模型。结果共行猪到食蟹猴异种节段小肠移植5例,移植肠肠长度为(52.0±5.7) cm,血管吻合成功率为100%,移植肠存活时间为(152±72) min(55~245 min)。结论本研究建立了猪到食蟹猴的异位小肠移植模型,模型稳定,可复性强,为进一步

  9. Modes of transmission and genetic diversity of foamy viruses in a Macaca tonkeana colony

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    Saib Ali

    2006-04-01

    Full Text Available Abstract Background Foamy viruses are exogenous complex retroviruses that are highly endemic in several animal species, including monkeys and apes, where they cause persistent infection. Simian foamy viral (SFV infection has been reported in few persons occupationally exposed to non-human primates (NHP in zoos, primate centers and laboratories, and recently in few hunters from central Africa. Most of the epidemiological works performed among NHP populations concern cross-sectional studies without long-term follow-up. Therefore, the exact timing and the modes of transmission of SFVs remain not well known, although sexual and oral transmissions have been suspected. We have conducted a longitudinal study in a free-breeding colony of Macaca tonkeana in order (1 to determine the prevalence of the infection by foamy viruses, (2 to characterize molecularly the viruses infecting such animals, (3 to study their genetic variability overtime by long-term follow-up of several DNA samples in a series of specific animals, and (4 to get new insights concerning the timing and the modes of SFVs primary infection in these monkeys by combining serology and molecular means, as well as studies of familial structures and long-term behavioral observations. Results/conclusion We first demonstrated that this colony was highly endemic for SFVs, with a clear increase of seroprevalence with age. Only 4.7% of immatures, and 43,7% of sub-adults were found seropositive, while 89.5% of adults exhibited antibodies directed against SFV. We further showed that 6 different strains of foamy viruses (exhibiting a very low intra-strain and overtime genetic variability in the integrase gene are circulating within this group. This suggests a possible infection by different strains within an animal. Lastly, we provide strong evidence that foamy viruses are mostly acquired through severe bites, mainly in sub-adults or young adults. Most cases of seroconversion occur after 7 years of age

  10. Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus

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    Laëtitia Maréchal

    2017-06-01

    Full Text Available Background Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. Methods The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus, affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants’ level of experience was defined as either: (1 naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2 exposed: shown pictures of the different Barbary macaques’ facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3 expert: worked with Barbary macaques for at least two months. Results Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques’ facial expressions improved the ability of inexperienced participants to better discriminate neutral

  11. Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Maréchal, Laëtitia; Levy, Xandria; Meints, Kerstin; Majolo, Bonaventura

    2017-01-01

    Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion) affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus, affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants' level of experience was defined as either: (1) naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2) exposed: shown pictures of the different Barbary macaques' facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3) expert: worked with Barbary macaques for at least two months. Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques' facial expressions improved the ability of inexperienced participants to better discriminate neutral and distressed faces, and a trend was found for

  12. Mitochondrial DNA variation in Chinese and Indian rhesus macaques (Macaca mulatta).

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    Smith, David Glenn; McDonough, John

    2005-01-01

    DNA was extracted from the buffy coats or serum of 212 rhesus macaques (Macaca mulatta) sampled throughout the species' geographic range. An 835 base pair (bp) fragment of mitochondrial DNA (mtDNA) was amplified from each sample, sequenced, aligned, and used to estimate genetic distances from which phylogenetic trees were constructed. A tree that included sequences from rhesus macaques whose exact origins in China are known was used to determine the regional origin of clusters of haplotypes, or haplogroups, defined by the trees. Indian rhesus sequences formed one large homogeneous haplogroup with very low levels of nucleotide diversity and no geographic structure, and a second much smaller haplogroup apparently derived from Burma. The sequences from Burma and eastern and western China were quite divergent from those in the major haplogroup of India. Each of these sequences formed separate clusters of haplotypes that exhibited far greater nucleotide diversity and/or population structure. Correspondingly, sequences from Indian rhesus macaques that are considered to represent different subspecies (based on morphological differences) were intermingled in the tree, while those from China reflected some, but not all, aspects of subspecific taxonomy. Regional variation contributed 72% toward the paired differences between sequences in an analysis of molecular variance (AMOVA), and the average differences between the populations of eastern and western China were also statistically significant. These results suggest that Indian and Chinese rhesus macaques were reproductively isolated during most, if not all, of the Pleistocene, during which time Indian rhesus macaques experienced a severe genetic bottleneck, and that some gene flow westward into India was subsequently reestablished. Samples from breeding centers in three different provinces of China included sequences from rhesus macaques that originated in both eastern (or southern) and western China, confirming anecdotal

  13. Modification of the Fc Region of a Human Anti-oncostatin M Monoclonal Antibody for Higher Affinity to FcRn Receptor and Extension of Half-life in Cynomolgus Monkeys.

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    Nnane, Ivo P; Han, Chao; Jiao, Qun; Tam, Susan H; Davis, Hugh M; Xu, Zhenhua

    2017-01-28

    The purpose of this study was to evaluate the pharmacokinetics (PK) of anti-oncostatin M (OSM) IgG1 monoclonal antibodies, CNTO 1119 and its Fc variant (CNTO 8212), which incorporates the LS(Xtend) mutation to extend terminal half-life (T1/2 ), after a single intravenous (IV) or subcutaneous (SC) administration in cynomolgus monkeys, and to predict human PK. In study 1, single doses of CNTO 1119 and CNTO 8212 were administered IV or SC at 3 mg/kg to cynomolgus monkeys (n = 3 per group). In study 2, single doses of CNTO 8212 were administered IV at 1, 5 or 20 mg/kg, or SC at 5 mg/kg to cynomolgus monkeys (n = 5 per group). Serial blood samples were collected for assessment of serum concentrations of CNTO 1119 and/or CNTO 8212. A two-compartment population PK model with first-order elimination was utilized to simultaneously describe the serum concentrations of CNTO 1119 and CNTO 8212 over time after IV and SC administration in cynomolgus monkeys. The typical population PK parameter estimates for CNTO 1119 in cynomolgus monkeys were clearance (CL) = 2.81 mL/day/kg, volume of distribution of central compartment (V1 ) = 31.3 mL/kg, volume of distribution of peripheral compartment (V2 ) = 23.3 mL/kg, absolute bioavailability (F) = 0.84 and T1/2 = 13.4 days. In comparison, the typical population PK parameter estimates for CNTO 8212 in cynomolgus monkeys were CL = 1.41 mL/day/kg, V1 = 39.8 mL/kg, V2 = 32.6 mL/kg, F = 0.75 and T1/2 = 35.7 days. The mean CL of CNTO 8212 was ~50% lower compared with that for CNTO 1119 in cynomolgus monkeys. The overall volume of distribution (V1 +V2 ) for CNTO 8212 was about 32% larger compared with that for CNTO 1119, but generally similar to the vascular volume in cynomolgus monkeys. The T1/2 of CNTO 8212 was significantly (p monkeys. Thus, the modification of the Fc portion of an anti-OSM IgG1 mAb for higher FcRn binding affinity resulted in lower systemic clearance and a longer terminal half-life in cynomolgus monkeys. CNTO 8212

  14. AcEST: BP921657 [AcEST

    Lifescience Database Archive (English)

    Full Text Available cul... 33 1.4 sp|Q6UY87|BEST1_MACFA Bestrophin-1 OS=Macaca fascicularis GN=BES... 30 6.7 >sp|P57999|ZAN_RABI... 812 QLVDSRGVFKTCLLHLKASSFFDNCVFDTCNFQGLQLMLCAHMS 855 >sp|Q6UY87|BEST1_MACFA Bestrophin-1 OS=Macaca fascicul

  15. Efeito do CO2 e etileno no período de dormência de minitubérculos de batata cv. Macaca Effect of CO2 and ethylene on the dormancy period of potato cv. Macaca minitubers

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    Dilson Antônio Bisognin

    2007-06-01

    Full Text Available Avaliou-se o efeito do CO2 e etileno no período de dormência de minitubérculos de batata da cultivar Macaca produzidos em telado durante duas safras. Imediatamente após a colheita, os minitubérculos foram submetidos aos tratamentos de abafamento com etileno (1000 mL L-1 por 72 h; CO2 (20% por 72 h; carbureto de cálcio (200 g m-3 por 72 h; e 1-metilciclopropeno (1-MCP (1mL L-1 por 24 h (apenas na safrinha; e imersão em solução de ethephon (840 mg L-1 por 5 s. A testemunha não recebeu nenhum tratamento. O delineamento experimental foi um fatorial (safras x tratamentos no inteiramente casualizado, com quatro repetições de 15 minitubérculos. Em intervalos semanais foram avaliadas a respiração e a produção de etileno. A cada 15 dias avaliou-se o número de brotos e a percentagem de tubérculos brotados, calculando-se a área abaixo da curva de progressão. Os minitubérculos produzidos durante a safra, comparados com os da safrinha, apresentaram menor período de dormência e aumentaram a taxa respiratória durante o período de armazenamento, claramente relacionados com a brotação dos minitubérculos. O CO2 e etileno não promoveram o encurtamento, enquanto que o 1-MCP prolongou o período de dormência de minitubérculos de batata cv. Macaca.The effect of CO2 and ethylene treatments were evaluated on the dormancy period of 'Macaca' minitubers produced in greenhouse during two growing seasons. Minitubers were treated soon after harvesting. The treatments were suffocation with ethylene (1000 mL L-1 during 72 h; CO2 (20 % during 72 h; calcium carburet (200 g m-3 during 72 h; and 1-methylcyclopropene (1-MCP (1 mL L-1 during 24 h (only for second season; and immersion with 2-cloroetil fosfonic acid (840 mg L-1 during 5 s. Control minitubers did not receive any treatment. The experiment was a factorial (seasons x treatments in a randomized design, with four replications of 15 minitubers. Respiration and ethylene production were

  16. Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus macaques following short-term early antiretroviral therapy.

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    Gülşen Ozkaya Sahin

    Full Text Available Neutralizing antibodies (NAb able to react to heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required in order to understand the factors contributing to induction of cross-reactive NAb responses. Here a well-established model of experimental pathogenic infection in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used to study the NAb response as well as the viral evolution of the highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously with SIVmac239. Antiretroviral therapy (ART was initiated ten days post-inoculation and administered daily for four months. Viral load, CD4(+ T-cell counts, total IgG levels, and breadth as well as strength of NAb in plasma were compared simultaneously over 14 months. In addition, envs from plasma samples were sequenced at three time points in all animals in order to assess viral evolution. We report here that seven of the 12 animals controlled viremia to below 10(4 copies/ml of plasma after discontinuation of ART and that this control was associated with a low level of evolutionary divergence. Macaques that controlled viral load developed broader NAb responses early on. Furthermore, escape mutations, such as V67M and R751G, were identified in virus sequenced from all animals with uncontrolled viremia. Bayesian estimation of ancestral population genetic diversity (PGD showed an increase in this value in non-controlling or transient-controlling animals during the first 5.5 months of infection, in contrast to virus-controlling animals. Similarly, non- or transient controllers displayed more positively-selected amino-acid substitutions. An early increase in PGD, resulting in the generation of positively-selected amino-acid substitutions, greater divergence and relative high viral load after ART withdrawal, may have contributed to the generation of potent NAb in several animals after SIVmac239 infection

  17. Contrasting the edge- and surface-based theories of object recognition: behavioral evidence from macaques (Macaca mulatta).

    Science.gov (United States)

    Parron, Carole; Washburn, David

    2010-01-01

    This study assessed the contribution of edge and surface cues on object representation in macaques (Macaca mulatta). In Experiments 1 and 2, 5 macaques were trained to discriminate 4 simple volumetric objects (geons) and were subsequently tested for their ability to recognize line drawings, silhouettes, and light changes of these geons. Performance was above chance in all test conditions and was similarly high for the line drawings and silhouettes of geons, suggesting the use of the outline shape to recognize the original objects. In addition, transfer for the geons seen under new lighting was greater than for the other stimuli, stressing the importance of the shading information. Experiment 3, using geons filled with new textures, showed that a radical change in the surface cues does not prevent object recognition. It is concluded that these findings support a surface-based theory of object recognition in macaques, although it does not exclude the contribution of edge cues, especially when surface details are not available.

  18. Land use in semi-free ranging Tonkean macaques Macaca tonkeana depends on environmental conditions: A geographical information system approach

    Institute of Scientific and Technical Information of China (English)

    Cédric SUEUR; Paul SALZE; Christiane WEBER; Odile PETIT

    2011-01-01

    Wild animals use their habitat according to ecological pressures such as predaton, resource availability or temperature, yet little is known about how individuals use their environment in semi free-ranging conditions. We assessed whether a semi-free ranging group of Tonkean macaques Macaca tonkeana used its wooded parkland in a heterogeneous way. GIS and GPS were used to determine whether individuals adjusted their behaviors according to variation in environmental constraints over time of day and the course of a year. We demonstrated that social and resting activities occurred in high altitude areas and areas with a high density of bushes, whereas the group foraged in areas where the density of bushes and grass was low. In general, the animals used areas exposed to the sun that were not on a slope. Semi-free ranging Tonkean macaques seemed to behave like their wild counterparts in terms of activity budget, land use per activity and thermoregulation.

  19. Evidence of Placentophagia and Mother-Infant Cannibalism in Free-Ranging Macaca mulatta tcheliensis in Mount Taihangshan, Jiyuan, China.

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    Tian, Jundong; Zhang, Shiqiang; Guo, Yongman; Garber, Paul A; Guo, Weijie; Kuang, San''ao; Lu, Jiqi

    2016-01-01

    Placentophagia or the consumption of the afterbirth is reported in many primate species, whereas cannibalism is a relatively rare event. Based on our field observations over the course of 3 years, we present evidence of placentophagia and mother-infant cannibalism in a free-ranging population of the Taihangshan macaque, Macaca mulatta tcheliensis, in the Mt. Taihangshan area, Jiyuan, Henan, China. We documented 1 case in which a mother consumed the afterbirth of her infant. In a second instance, we observed a fresh placenta discarded on the ground by an unknown individual. We also present a description of the first documented instance of mother-infant cannibalism in the same group of free-ranging rhesus macaques. © 2017 S. Karger AG, Basel.

  20. Locally infiltrative ameloblastic fibroma in a rhesus macaque (Macaca mulatta) with characterizations of its proliferating activity and biological behavior.

    Science.gov (United States)

    Liu, David X; Doyle, Lara A; Bouljihad, Mostafa T; Didier, Peter J; Gilbert, Margaret H; Wang, Xiaolei; Pahar, Bapi; Bohm, Rudolf P; Veazey, Ronald S; Lackner, Andrew A

    2012-05-01

    An 8-year-old male rhesus macaque (Macaca mulatta) presented with unilateral enlargement of the left mandible. Radiographs revealed a marked expansion of the left mandible with a multilocular radiolucent mass with abundant osteolysis. The mass was grossly firm, fleshy, and gelatinous on the cut surface. Histologically, the mass was locally infiltrative and composed of neoplastic epithelial and mesenchymal components that stained positive for cytokeratin and vimentin, respectively. Occasional densely spherical condensations of fibroblasts resembling the cap stage of odontogenesis were present in the mesenchyma. Immunohistochemical staining with Ki-67, S-100, and CD34 indicated that both epithelial and mesenchymal components of the neoplasm had low proliferation. Alcian blue, periodic acid-Schiff, and trichrome stains showed an immature stromal component with no collagen formation. Based on the clinical, histologic, and immunophenotypic features, the tumor was identified as a locally infiltrative ameloblastic fibroma.

  1. Comparison of noncontact infrared thermometry and 3 commercial subcutaneous temperature transponding microchips with rectal thermometry in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Brunell, Marla K

    2012-07-01

    This study compared a noncontact infrared laser thermometer and 3 different brands of subcutaneous temperature transponding microchips with rectal thermometry in 50 rhesus macaques (Macaca mulatta). The data were analyzed by using intraclass correlation coefficients and limits of agreement. In addition, the technical capabilities and practicality of the thermometers in the clinical setting were reviewed. None of the alternative techniques investigated was equivalent to rectal thermometry in rhesus macaques. Temperatures obtained by using microchips had higher correlation and agreed more closely with rectal temperatures than did those obtained by the noncontact infrared method. However, transponding microchips did not yield consistent results. Due to difficulty in positioning nonsedated macaques in their homecage, subcutaneous microchips were not practical in the clinical setting. Furthermore, pair-housed macaques may be able to break or remove microchips from their cagemates.

  2. Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus

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    Song Ruijiang

    2009-07-01

    Full Text Available Abstract Background Although pig-tailed macaques (Macaca nemestrina have been used in AIDS research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (Macaca mulatta. Similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (SIV, but less so for chimeric simian-human immunodeficiency viruses (SHIV, although the latter have been widely used in HIV vaccine studies. Here, we report the consequences of intrarectal infection with a CCR5-tropic clade C SHIV-1157ipd3N4 in pig-tailed macaques. Results Plasma and cell-associated virus was detectable in peripheral blood and intestinal tissues of all four pig-tailed macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed a rapid and irreversible loss of CD4+ T cells at multiple mucosal sites, resulting in a marked decrease of CD4:CD8 T cell ratios 0.5–4 weeks after inoculation. This depletion targeted subsets of CD4+ T cells expressing the CCR5 coreceptor and having a CD28-CD95+ effector memory phenotype, consistent with the R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the acute phase seroconverted as early as week 4, with two developing cross-clade neutralizing antibody responses by week 24. These two animals also demonstrated persistent plasma viremia for >48 weeks. One of these animals developed AIDS, as shown by peripheral blood CD4+ T-cell depletion starting at 20 weeks post inoculation. Conclusion These findings indicate that SHIV-1157ipd3N4-induced pathogenesis in pig-tailed macaques followed a similar course as SIV-infected rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a useful and relevant model for AIDS vaccine and pathogenesis research.

  3. Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

    Science.gov (United States)

    Burrows, Anne M; Waller, Bridget M; Micheletta, Jérôme

    2016-10-01

    Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc.

  4. Immunochemical quantification of cynomolgus CYP2J2, CYP4A and CYP4F enzymes in liver and small intestine.

    Science.gov (United States)

    Uehara, Shotaro; Murayama, Norie; Nakanishi, Yasuharu; Nakamura, Chika; Hashizume, Takanori; Zeldin, Darryl C; Yamazaki, Hiroshi; Uno, Yasuhiro

    2015-02-01

    1. An increasing number of studies have indicated the roles of CYP4 proteins in drug metabolism; however, CYP4 expression has not been measured in cynomolgus monkeys, an important animal species for drug metabolism studies. 2. In this study, cynomolgus CYP4A11, CYP4F2/3, CYP4F11 and CYP4F12, along with CYP2J2, were immunoquantified using selective antibodies in 28 livers and 35 small intestines, and their content was compared with CYP1A, CYP2A, CYP2B6, CYP2C9/19, CYP2D, CYP2E1, CYP3A4 and CYP3A5, previously quantified. 3. In livers, CYP2J2, CYP4A11, CYP4F2/3, CYP4F11 and CYP4F12, varied 1.3- to 4.3-fold, represented 11.2, 14.4, 8.0, 2.7 and 0.3% of total immunoquantified CYP1-4 proteins, respectively. 4. In small intestines, CYP2J2, CYP4F2/3, CYP4F11 and CYP4F12, varied 2.4- to 9.7-fold, represented 6.9, 36.4, 2.4 and 9.3% of total immunoquantified CYP1-4 proteins, respectively, making CYP4F the most abundant P450 subfamily in small intestines. CYP4A11 was under the detection limit in all of the samples analyzed. 5. Significant correlations were found in liver for CYP4A11 with lauric acid 11-/12-hydroxylation and for CYP4F2/3 and CYP4F11 with astemizole hydroxylation. 6. This study revealed the relatively abundant contents of cynomolgus CYP2J2, CYP4A11 and CYP4Fs in liver and/or small intestine, suggesting their potential roles for the metabolism of xenobitotics and endogenous substrates.

  5. Cynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease.

    Science.gov (United States)

    Vitelli-Avelar, Danielle Marquete; Sathler-Avelar, Renato; Mattoso-Barbosa, Armanda Moreira; Gouin, Nicolas; Perdigão-de-Oliveira, Marcelo; Valério-Dos-Reis, Leydiane; Costa, Ronaldo Peres; Elói-Santos, Silvana Maria; Gomes, Matheus de Souza; Amaral, Laurence Rodrigues do; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Dick, Edward J; Hubbard, Gene B; VandeBerg, Jane F; VandeBerg, John L

    2017-02-01

    Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease. In this cross-sectional study design, flow cytometry and systems biology approaches were used to characterize the ex vivo and in vitro T. cruzi-specific functional cytokine signature of circulating leukocytes from TcI-T. cruzi naturally infected cynomolgus macaques (CH). Results showed that CH presented an overall CD4+-derived IFN-γ pattern regulated by IL-10-derived from CD4+ T-cells and B-cells, contrasting with the baseline profile observed in non-infected hosts (NI). Homologous TcI-T. cruzi-antigen recall in vitro induced a broad pro-inflammatory cytokine response in CH, mediated by TNF from innate/adaptive cells, counterbalanced by monocyte/B-cell-derived IL-10. TcIV-antigen triggered a more selective cytokine signature mediated by NK and T-cell-derived IFN-γ with modest regulation by IL-10 from T-cells. While NI presented a cytokine network comprised of small number of neighborhood connections, CH displayed a complex cross-talk amongst network elements. Noteworthy, was the ability of TcI-antigen to drive a complex global pro-inflammatory network mediated by TNF and IFN-γ from NK-cells, CD4+ and CD8+ T-cells, regulated by IL-10+CD8+ T-cells, in contrast to the TcIV-antigens that trigger a modest network, with moderate connecting edges. Altogether, our findings demonstrated that CH present a pro-inflammatory/regulatory cytokine signature similar to that observed in human Chagas disease. These data bring additional insights that further validate these non

  6. Cynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease

    Science.gov (United States)

    Mattoso-Barbosa, Armanda Moreira; Gouin, Nicolas; Perdigão-de-Oliveira, Marcelo; Valério-dos-Reis, Leydiane; Costa, Ronaldo Peres; Elói-Santos, Silvana Maria; Gomes, Matheus de Souza; do Amaral, Laurence Rodrigues; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Dick, Edward J.; Hubbard, Gene B.; VandeBerg, Jane F.; VandeBerg, John L.

    2017-01-01

    Background Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease. Methods and findings In this cross-sectional study design, flow cytometry and systems biology approaches were used to characterize the ex vivo and in vitro T. cruzi-specific functional cytokine signature of circulating leukocytes from TcI-T. cruzi naturally infected cynomolgus macaques (CH). Results showed that CH presented an overall CD4+-derived IFN-γ pattern regulated by IL-10-derived from CD4+ T-cells and B-cells, contrasting with the baseline profile observed in non-infected hosts (NI). Homologous TcI-T. cruzi-antigen recall in vitro induced a broad pro-inflammatory cytokine response in CH, mediated by TNF from innate/adaptive cells, counterbalanced by monocyte/B-cell-derived IL-10. TcIV-antigen triggered a more selective cytokine signature mediated by NK and T-cell-derived IFN-γ with modest regulation by IL-10 from T-cells. While NI presented a cytokine network comprised of small number of neighborhood connections, CH displayed a complex cross-talk amongst network elements. Noteworthy, was the ability of TcI-antigen to drive a complex global pro-inflammatory network mediated by TNF and IFN-γ from NK-cells, CD4+ and CD8+ T-cells, regulated by IL-10+CD8+ T-cells, in contrast to the TcIV-antigens that trigger a modest network, with moderate connecting edges. Conclusions Altogether, our findings demonstrated that CH present a pro-inflammatory/regulatory cytokine signature similar to that observed in human Chagas disease. These data bring additional

  7. 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.

  8. Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy

    Science.gov (United States)

    Guimarães, Juliana Rodrigues; Melgaço, Juliana Gil; Kevorkian, Yohan Britto; Bottino, Fernanda de Oliveira; Vieira, Yasmine Rangel; da Silva, Aline Campos de Azevedo; Pinto, Douglas Pereira; da Fonseca, Laís Bastos; Vilhena, Leandro Schiavo; Uiechi, Edilson; da Silva, Maria Cristina Carlan; Moran, Julio; Marchevsky, Renato Sérgio; Cruz, Oswaldo Gonçalves; Otonel, Rodrigo Alejandro Arellano; Alfieri, Amauri Alcindo; de Oliveira, Jaqueline Mendes; Gaspar, Ana Maria Coimbra; Pinto, Marcelo Alves

    2017-01-01

    Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis

  9. Eldecalcitol, a vitamin D analog, reduces bone turnover and increases trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys.

    Science.gov (United States)

    Smith, Susan Y; Doyle, Nancy; Boyer, Marilyne; Chouinard, Luc; Saito, Hitoshi

    2013-11-01

    Vitamin D insufficiency is common in elderly people worldwide, and intake of supplementary calcium and vitamin D is recommended to those with a high risk of fracture. Several clinical studies and meta-analyses have shown that calcium and vitamin D supplementation reduces osteoporotic fractures, and a strong correlation exists between vitamin D status and fracture risk. Vitamin D supplementations improve calcium balance in the body; however, it remains unclear whether vitamin D directly affects bone metabolism. Recently, eldecalcitol (ELD), an active form of vitamin D analog, has been approved for the treatment of osteoporosis in Japan. A 3-year clinical trial showed ELD treatment increased lumbar spine bone mineral density (BMD) and reduced fracture risk in patients with osteoporosis. To evaluate the mechanism of ELD action in bone remodeling, ovariectomized cynomolgus monkeys were treated with 0.1 or 0.3μg/day of ELD for 6months. This treatment increased lumbar BMD by 4.4% and 10.2%, respectively, and suppressed ovariectomy-induced increases in bone turnover markers compared to OVX-vehicle control. Histomorphometric analysis of bone revealed that both bone formation parameters and bone resorption parameters in the trabecular bone of the lumbar vertebrae were suppressed by ELD treatment. ELD treatment also improved biomechanical properties of the lumbar vertebrae and the femoral neck in the ovariectomized cynomolgus monkeys. These results indicate that, in a bone-remodeling animal model, ELD increases BMD and improves bone biomechanical properties by normalizing bone turnover. Therefore, ELD has a direct and potentially beneficial effect on bone metabolism. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Mycobacterium tuberculosis infections in cynomolgus monkey transplant recipients and institution of a screening program for the prevention and control of tuberculosis.

    Science.gov (United States)

    Choi, Eun Wha; Lee, Kyo Won; Kim, Tae Min; Park, Hyojun; Jeon, Mi Ri; Cho, Chan Woo; Park, Jae Berm; Kim, Sungjoo

    2016-12-20

    Tuberculosis is a major health concern in not only humans, but also in non-human primates. In this paper, we report recent cases of Mycobacterium tuberculosis in cynomolgus monkeys from Cambodia used in transplantation research in a Korean facility and describe a program instituted to prevent and control subsequent infections. All monkeys were antibody negative for tuberculosis during quarantine; however, suspected tuberculosis gross lesions were observed in two cynomolgus monkeys who underwent allograft kidney transplantation. Lung tissue from one monkey was found to be weakly positive by PCR for detection of M. tuberculosis. After PCR confirmation of tuberculosis, we decided to sacrifice the remaining animals and instituted a program for preventing subsequent infections. During necropsy of the remaining monkeys, two additional suspected tuberculosis cases were observed. A total of four monkeys with nodular lesions in the respiratory tract, suspected to be tuberculosis, demonstrated no clinical signs. Acid-fast bacilli were identified on slides from the lung or liver in all four monkeys. Two of four monkeys tested PCR positive. We decided that new monkeys entering from Cambodia should undergo a single gastric aspiration PCR and tuberculin skin testing (TST) every 2 weeks until four consecutive negatives to detect latent tuberculosis are obtained before starting experiments. Monkeys should then undergo a chest X-ray monthly and TST every 6 months. Detection of latent tuberculosis by an effective preventive screening program before starting experiments is an essential process to reduce the risk of reactivation of tuberculosis, especially in studies using immunosuppressive drugs. It also serves to protect the health of captive non-human primates, their caretakers and researchers.

  11. 我国广西食蟹猴养殖场2种血液寄生原虫感染调查%Investigation of two blood parasitic protozoa infection in farmed Macaca fascicularis in Guangxi Zhuang Autonomous Region

    Institute of Scientific and Technical Information of China (English)

    路媛媛; 彭恒; 朱淮民; 李健; 薛绍礼

    2016-01-01

    目的 调查我国广西壮族自治区某食蟹猴养殖场血液寄生原虫感染状况,为人体血液寄生原虫的防控提供科学依据.方法 采集广西壮族自治区南宁市某食蟹猴养殖场猴血液样本993份,全部制作FTA卡样本,涂制薄血膜550份.将样本混合,以巢式PCR及普通PCR方法分别检测FTA卡保存的猴血样本中巴贝虫以及疟原虫.检测阳性组再分别进行单个样本检测,阳性样本对应的薄血膜进行姬姆萨染色后再镜检.结果 经巢式PCR检测,田鼠巴贝虫检出阳性率为6.95%(69/993);仅1例经PCR检出猪尾猴疟原虫阳性.22份PCR检测巴贝虫阳性的血液样本经染色镜检,共16份检出巴贝虫,其显微镜下观察到红细胞内有环状体,无疟色素.结论 我国广西地区食蟹猴的田鼠巴贝虫感染率较高,其可能在传播中起保虫宿主的作用;在筛查田鼠巴贝虫低密度感染时,巢式PCR方法敏感性较高.

  12. Comparative research of Symbiodinium diversity associated with two color morphs of reef-building coral Galaxea fascicularis%丛生盔形珊瑚的2种颜色群体共生藻组成比较

    Institute of Scientific and Technical Information of China (English)

    周国伟; 黄晖; 喻子牛; 尤丰; 李秀保

    2011-01-01

    造礁石珊瑚与共生藻 Symbiodinium spp.的互利共生对维护多样性极为丰富的珊瑚礁生态系统至关重要.在受到诸如水温异常等环境胁迫时,宿主珊瑚会排出体内共生藻而导致珊瑚白化直至死亡.造礁石珊瑚群体丰富的颜色对于珊瑚适应环境有着重要的作用,即使是同种造礁石珊瑚的不同群体,它们在颜色上也会有差异.丛生盔形珊瑚 Galaxea.fascicularis 作为印度-太平洋区系常见种广泛分布于海南三亚珊瑚礁海域,不同群体的颜色相异.对绿色和褐色2种颜色的丛生盔形珊瑚群体共生藻的28S rDNA进行限制性片段长度多态性(polymerase chainreaction-restrictionfragmentlength polymorphism,PCR-RFLP)分析,结果显示,该珊瑚可以与C和D系群共生藻分别或同时共生.此外,丛生盔形珊瑚2种颜色群体的共生藻组成并无显著差异,表明珊瑚群体的颜色差异与共生藻的组成并无直接联系.影响珊瑚表型颜色的因素复杂,包括珊瑚的绿色荧光蛋白(green fluorescent protein,GFP)、珊瑚和共生藻的各种色素等,具体机理需要进一步研究.%The symbiotic association between corals and Symbiodinium is a major contributing factor in the success of coral reef ecosystem with high biodiversity.Under stressful environmental conditions, such as abnormally high water temperatures, this symbiosis can break down and the zooxanthellae are lost in a process known as "bleaching", which can cause the death of corals if stresses are severe or persistent.Reef-building corals have diverse colors even in different colonies within the same species, and the color plays a key role in acclimation of coral to environment.Galaxea fascicularis is a common reef-building coral in the Indo-Pacific area, including the coral reef areas in Sanya, Hainan Island, and displays a variety colors even with different colonies.The authors used PCR-RFLP to investigate whether or not variation in color is associated

  13. Pandemic Swine-Origin H1N1 Influenza Virus Replicates to Higher Levels and Induces More Fever and Acute Inflammatory Cytokines in Cynomolgus versus Rhesus Monkeys and Can Replicate in Common Marmosets.

    Science.gov (United States)

    Mooij, Petra; Koopman, Gerrit; Mortier, Daniëlla; van Heteren, Melanie; Oostermeijer, Herman; Fagrouch, Zahra; de Laat, Rudy; Kobinger, Gary; Li, Yan; Remarque, Edmond J; Kondova, Ivanela; Verschoor, Ernst J; Bogers, Willy M J M

    2015-01-01

    The close immunological and physiological resemblance with humans makes non-human primates a valuable model for studying influenza virus pathogenesis and immunity and vaccine efficacy against infection. Although both cynomolgus and rhesus macaques are frequently used in influenza virus research, a direct comparison of susceptibility to infection and disease has not yet been performed. In the current study a head-to-head comparison was made between these species, by using a recently described swine-origin pandemic H1N1 strain, A/Mexico/InDRE4487/2009. In comparison to rhesus macaques, cynomolgus macaques developed significantly higher levels of virus replication in the upper airways and in the lungs, involving both peak level and duration of virus production, as well as higher increases in body temperature. In contrast, clinical symptoms, including respiratory distress, were more easily observed in rhesus macaques. Expression of sialyl-α-2,6-Gal saccharides, the main receptor for human influenza A viruses, was 50 to 73 times more abundant in trachea and bronchus of cynomolgus macaques relative to rhesus macaques. The study also shows that common marmosets, a New World non-human primate species, are susceptible to infection with pandemic H1N1. The study results favor the cynomolgus macaque as model for pandemic H1N1 influenza virus research because of the more uniform and high levels of virus replication, as well as temperature increases, which may be due to a more abundant expression of the main human influenza virus receptor in the trachea and bronchi.

  14. Eosinophilic bronchitis-like lesion as the cause of death in a Macaca mulatta: a first case report

    Science.gov (United States)

    Christal, J.L.; Hubbard, G.B.; Dick, E.J.; Brasky, K.M.; Jagirdar, J.

    2009-01-01

    Background Eosinophilic bronchitis is a recently described, relatively benign condition in humans that is characterized by a corticosteroid-responsive chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The exact cause of this condition is currently unknown, however has been associated with various occupational exposures in humans. It has also been reported to progress to irreversible airway obstruction. This disease has been reported in dogs and horses, but not in non-human primates. Methods Gross examination of an otherwise healthy 13-year-old, colony-born Macaca mulatta, which died of severe non-responsive respiratory distress revealed that the lungs were markedly inflated and moist. Results Hematoxylin and eosin-stained sections from the lungs contained widespread accumulation of eosinophils, sloughed epithelial cells, and mucus centered around bronchioles and adjacent airways. There was no evidence of mast cell infiltration of peribronchiolar smooth muscle, goblet cell hyperplasia, or basement membrane thickening. Conclusions This ruled out recurrent episodes as would be expected in asthma, favoring the diagnosis of an eosinophilic bronchitis-like lesion. We report a first case of eosinophilic bronchitis-like features in a M. mulatta. PMID:18333916

  15. Fasting induced kisspeptin signaling suppression is regulated by glutamate mediated cues in adult male rhesus macaque (Macaca mulatta).

    Science.gov (United States)

    Shamas, Shazia; Khan, Saeed-Ul-Hassan; Khan, Muhammad Yousaf; Shabbir, Nadia; Zubair, Hira; Shafqat, Saira; Wahab, Fazal; Shahab, Muhammad

    2015-08-01

    Kisspeptin signaling is suppressed by short term fasting. It has been reported that hypothalamic Kiss1 and Kiss1r mRNA expression decreased after 48h of fasting in male rhesus monkey. But the mechanism involved in the reduction of kisspeptin signaling after 48h of fasting is unknown. Recent studies have suggested the role of afferent excitatory and inhibitory pathways in the regulation of kisspeptin neurons. Therefore, this study was designed to observe the changes in the glutamate and GABA signaling during fed and 48h fasting states by performing immunofluorescence to examine the interaction of kisspeptin neurons with NR1 subunit of NMDA receptors and by performing SYBR green qRT-PCR to measure and quantify the levels of Kiss1, Kiss1r, NR1 and GAD67 mRNA in the POA and MBH of adult male rhesus macaque (Macaca mulatta) during 48h of fasting (n=2) and fed ad libitum (n=2). Plasma testosterone (pfasting. Our results clearly showed that expression of hypothalamic Kiss1, Kiss1r and NR1 mRNA was significantly (pfasting. These observations suggest that decreased kisspeptin signaling during fasting may occur due to reduction in glutamatergic inputs to kisspeptin neurons. Our results also suggest that fasting induced suppression of kisspeptin signaling is not mediated through GABAergic neurons.

  16. Neonatal imitation predicts infant rhesus macaque (Macaca mulatta) social and anxiety-related behaviours at one year

    Science.gov (United States)

    Kaburu, Stefano S. K.; Paukner, Annika; Simpson, Elizabeth A.; Suomi, Stephen J.; Ferrari, Pier F.

    2016-01-01

    The identification of early markers that predict the development of specific social trajectories is critical to understand the developmental and neurobiological underpinnings of healthy social development. We investigated, in infant rhesus macaques (Macaca mulatta), whether newborns’ capacity to imitate facial gestures is a valid predictive marker for the emergence of social competencies later in development, at one year of age. Here we first assessed whether infant macaques (N = 126) imitate lipsmacking gestures (a macaque affiliative expression) performed by a human experimenter in their first week of life. We then collected data on infants’ social interactions (aggression, grooming, and play) and self-scratching (a proxy indicator of anxiety) at 11–14 months when infants were transferred into a new enclosure with a large social group. Our results show that neonatal imitators exhibit more dominant behaviours, are less anxious, and, for males only, spend more time in play at one year old. These findings suggest that neonatal imitation may be an early predictor of infant sociality and may help identify infants at risk of neurodevelopmental social deficits. PMID:27725768

  17. Grooming-related feeding motivates macaques to groom and affects grooming reciprocity and episode duration in Japanese macaques (Macaca fuscata).

    Science.gov (United States)

    Onishi, Kenji; Yamada, Kazunori; Nakamichi, Masayuki

    2013-01-01

    Allogrooming is considered as an altruistic behavior wherein primates exchange grooming as a tradable commodity for reciprocal grooming or other commodities such as support during aggression and tolerance during co-feeding. First, we report a case of the grooming relationships of the lowest-ranking adult female in a group of Japanese macaques (Macaca fuscata). The female (Lp) had lost a portion of the fur and was groomed by higher-ranking individuals without providing reciprocal grooming or other commodities. The groomers probably fed on lice eggs from the fur of Lp more frequently than from that of other adult groomees. This suggests that grooming-related feeding (GRF) motivated many individuals to groom Lp and influenced grooming reciprocity in dyads. Second, we investigated quantitative grooming data for adult females. A high GRF rate was found to lengthen the duration of grooming, suggesting that GRF motivates groomers to groom. From these results, we proposed 2 possible reasons for groomers' sensitivity to GRF rate: (1) the nutritional benefit from GRF compensates for part of the cost of giving grooming and facilitates giving grooming and (2) groomer's sensitivity to the GRF rate maintains the efficiency of removing lice eggs and ensures the groomee's hygienic benefit in receiving grooming.

  18. Genetic variation between two Tibetan macaque (Macaca thibetana) populations in the eastern China based on mitochondrial DNA control region sequences.

    Science.gov (United States)

    Yao, Yongfang; Zhong, Lijing; Liu, Bofeng; Li, Jiayi; Ni, Qingyong; Xu, Huailiang

    2013-06-01

    Tibetan macaque (Macaca thibetana) is a threatened primate species endemic to China. Population genetic and phylogenetic analyses were conducted in 66 Tibetan individuals from Sichuan (SC), Huangshan (HS), and Fujian (FJ) based on a 477-bp fragment of mitochondrial DNA control region. Four new haplotypes were defined, and a relatively high level of genetic diversity was first observed in FJ populations (Hd = 0.7661). Notably, a continuous approximately 10 bp-fragment deletion was observed near the 5' end of the mtDNA control region of both HS and FJ populations when compared with that of SC population, and a sharing haplotype was found between the two populations, revealing a closer genetic relationship. However, significant genetic differentiation (FST = 0.8700) and more poor gene exchange (Nm < 1) had occurred among three populations. This study mainly provide a further insight into the genetic relationship between HS and FJ Tibetan macaque populations, but it may be necessary to carry out further study with extra samples from other locations in the geographic coverage of the two subspecies (M. thibetana pullus and M. thibetana huangshanensis).

  19. Influence of dominance rank and affiliation relationships on self-directed behavior in female Tibetan macaques (Macaca thibetana).

    Science.gov (United States)

    Zhang, Qi-Xin; Li, Jin-Hua; Xia, Dong-Po; Zhu, Yong; Wang, Xi; Zhang, Dao

    2014-05-01

    Self-directed behavior (SDB) is characterized as an indicator of anxiety, frustration and stress in nonhuman primates. In this study, we collected self-directed behavior data from one group of free-ranging Tibetan macaques (Macaca thibetana) at Mt. Huangshan, China (September 2012-May 2013) using a combination of behavioral sampling methods including focal animal sampling, behavioral sampling, continuous sampling and instantaneous sampling. Our results showed that females engaged in significantly higher rates of self-directed behavior when they were in proximity to dominant individuals compared to subordinate ones. Conflict losers significantly increased their SDB rates after agonistic episodes, indicating that SDB might also serve as an index of anxiety in M. thibetana. We further found that females significantly increased their SDB rates when focal individual was proximity to weakly affiliation relationship higher rank members than to strongly affiliation relationship higher rank members. If conflicts were not reconciled, the postconflict SDB rates of losers were higher when they stayed with strongly affiliation opponents; if conflicts were reconciled, victims of strongly affiliation relationships opponents engaged in more SDB rates before reconciliation than after reconciliation, while victims of moderately affiliation relationships opponents did not engaged in more SDB rates before reconciliation than after reconciliation. We conclude that both of dominance rank and affiliation relationships might both influence the SDB rates of female Tibetan macaques significantly, suggesting that SDB is not only an index of anxiety in Tibetan macaques, but also can provide a new insight into evaluation of social relationships between individuals.

  20. Analysis of immunoglobulin, complements and CRP levels in serum of captive northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Zhang, Xiao-Liang; Pang, Wei; Deng, De-Yao; Lv, Long-Bao; Feng, Yue; Zheng, Yong-Tang

    2014-05-01

    The northern pig-tailed macaque (NPM,Macaca leonina) has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northern pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age (P>0.05), while serum IgG levels increased progressively with age (r=0.202;P=0.045). Serum IgG, IgA, IgM and C3 levels were higher in females than in males (P<0.05). Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 (r=0.700; P<0.0001). This study provides basic serum immunoglobulin and complement data of captive northern pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.

  1. Intergroup variation in stable isotope ratios reflects anthropogenic impact on the Barbary macaques (Macaca sylvanus) of Gibraltar.

    Science.gov (United States)

    Schurr, Mark R; Fuentes, Agustín; Luecke, Ellen; Cortes, John; Shaw, Eric

    2012-01-01

    Interactions with humans impact many aspects of behavior and ecology in nonhuman primates. Because of the complexities of the human-nonhuman primate interface, methods are needed to quantify the effects of anthropogenic interactions, including their intensity and differential impacts between nonhuman primate groups. Stable isotopes can be used to quickly and economically assess intergroup dietary variation, and provide a framework for the development of specific hypotheses about anthropogenic impact. This study uses stable carbon and nitrogen isotope analysis to examine intraspecific variation in diet between five groups of Barbary macaques, Macaca sylvanus, in the Upper Rock Nature Reserve, Gibraltar. Analysis of hair from 135 macaques showed significant differences in δ(13)C and δ(15)N values between a group with minimal tourist contact and groups that were main tourist attractions. Because we observed no overt physiological or substantial behavioral differences between the groups, feeding ecology is the most likely cause of any differences in stable isotope ratios. Haphazard provisioning by tourists and Gibraltarians is a likely source of dietary variation between groups. Stable isotope analysis and observational data facilitate a deeper understanding of the feeding ecology of the Barbary macaques relevant to the role of an anthropogenic ecology for the species.

  2. Expression analysis of taste signal transduction molecules in the fungiform and circumvallate papillae of the rhesus macaque, Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Yoshiro Ishimaru

    Full Text Available The molecular mechanisms of the mammalian gustatory system have been examined in many studies using rodents as model organisms. In this study, we examined the mRNA expression of molecules involved in taste signal transduction in the fungiform papillae (FuP and circumvallate papillae (CvP of the rhesus macaque, Macaca mulatta, using in situ hybridization. TAS1R1, TAS1R2, TAS2Rs, and PKD1L3 were exclusively expressed in different subsets of taste receptor cells (TRCs in the FuP and CvP. This finding suggests that TRCs sensing different basic taste modalities are mutually segregated in macaque taste buds. Individual TAS2Rs exhibited a variety of expression patterns in terms of the apparent level of expression and the number of TRCs expressing these genes, as in the case of human TAS2Rs. GNAT3, but not GNA14, was expressed in TRCs of FuP, whereas GNA14 was expressed in a small population of TRCs of CvP, which were distinct from GNAT3- or TAS1R2-positive TRCs. These results demonstrate similarities and differences between primates and rodents in the expression profiles of genes involved in taste signal transduction.

  3. Individual differences in scanpaths correspond with serotonin transporter genotype and behavioral phenotype in rhesus monkeys (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Robert R Gibboni

    2009-11-01

    Full Text Available Scanpaths (the succession of fixations and saccades during spontaneous viewing contain information about the image but also about the viewer. To determine the viewer-dependent factors in the scanpaths of monkeys, we trained three adult males (Macaca mulatta to look for 3 s at images of conspecific facial expressions with either direct or averted gaze. The subjects showed significant differences on four basic scanpath parameters (number of fixations, fixation duration, saccade length, and total scanpath length when viewing the same facial expression/gaze direction combinations. Furthermore, we found differences between monkeys in feature preference and in the temporal order in which features were visited on different facial expressions. Overall, the between-subject variability was larger than the within- subject variability, suggesting that scanpaths reflect individual preferences in allocating visual attention to various features in aggressive, neutral, and appeasing facial expressions. Individual scanpath characteristics were brought into register with the genotype for the serotonin transporter regulatory gene (5-HTTLPR and with behavioral characteristics such as expression of anticipatory anxiety and impulsiveness/hesitation in approaching food in the presence of a potentially dangerous object.

  4. MaqFACS (Macaque Facial Action Coding System) can be used to document facial movements in Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Julle-Danière, Églantine; Micheletta, Jérôme; Whitehouse, Jamie; Joly, Marine; Gass, Carolin; Burrows, Anne M; Waller, Bridget M

    2015-01-01

    Human and non-human primates exhibit facial movements or displays to communicate with one another. The evolution of form and function of those displays could be better understood through multispecies comparisons. Anatomically based coding systems (Facial Action Coding Systems: FACS) are developed to enable such comparisons because they are standardized and systematic and aid identification of homologous expressions underpinned by similar muscle contractions. To date, FACS has been developed for humans, and subsequently modified for chimpanzees, rhesus macaques, orangutans, hylobatids, dogs, and cats. Here, we wanted to test whether the MaqFACS system developed in rhesus macaques (Macaca mulatta) could be used to code facial movements in Barbary macaques (M. sylvanus), a species phylogenetically close to the rhesus macaques. The findings show that the facial movement capacity of Barbary macaques can be reliably coded using the MaqFACS. We found differences in use and form of some movements, most likely due to specializations in the communicative repertoire of each species, rather than morphological differences.

  5. Associations between Parity, Hair Hormone Profiles during Pregnancy and Lactation, and Infant Development in Rhesus Monkeys (Macaca mulatta).

    Science.gov (United States)

    Dettmer, Amanda M; Rosenberg, Kendra L; Suomi, Stephen J; Meyer, Jerrold S; Novak, Melinda A

    2015-01-01

    Studies examining hormones throughout pregnancy and lactation in women have been limited to single, or a few repeated, short-term measures of endocrine activity. Furthermore, potential differences in chronic hormonal changes across pregnancy/lactation between first-time and experienced mothers are not well understood, especially as they relate to infant development. Hormone concentrations in hair provide long-term assessments of hormone production, and studying these measures in non-human primates allows for repeated sampling under controlled conditions that are difficult to achieve in humans. We studied hormonal profiles in the hair of 26 female rhesus monkeys (Macaca mulatta, n=12 primiparous), to determine the influences of parity on chronic levels of cortisol (hair cortisol concentration, HCC) and progesterone (hair progesterone concentration, HPC) during early- to mid-pregnancy (PREG1), in late pregnancy/early lactation (PREG2/LACT1), and in peak lactation (LACT2). We also assessed infants' neurobehavioral development across the first month of life. After controlling for age and stage of pregnancy at the first hair sampling period, we found that HCCs overall peaked in PREG2/LACT1 (p=0.02), but only in primiparous monkeys (ppregnancy and lactation for all monkeys (phormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in mothers with varied caretaking experience. In addition, infant exposure to relatively higher levels of maternal cortisol during the late fetal and early postnatal periods is predictive of poorer developmental outcomes.

  6. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

    Science.gov (United States)

    Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

    2015-01-01

    The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research.

  7. Cashing out: The decisional flexibility of uncertainty responses in rhesus macaques (Macaca mulatta) and humans (Homo sapiens).

    Science.gov (United States)

    Zakrzewski, Alexandria C; Perdue, Bonnie M; Beran, Michael J; Church, Barbara A; Smith, J David

    2014-10-01

    Researchers are exploring whether animals share with humans something like a metacognitive capacity. Though some results point to human-animal continuities in this domain, they face the dominant criticism that animals' performances might be associative. A persistent problem is that animal-metacognition paradigms present static environments of risk and reward that may foster inflexible and conditioned responding. Those environments do not challenge animals to show the flexibility in their decision strategies that could indicate an antecedent capacity to metacognition. Accordingly, we tested macaques and humans on an uncertainty-monitoring paradigm in which risk changed dynamically. Participants classified stimuli of different difficulties while also choosing when to use a cashout response to collect the accumulated rewards that would be forfeit on a discrimination error. Macaques (Macaca mulatta) and humans flexibly adjusted their decision criteria to achieve appropriate protection against the cost of error that could differ depending on trial difficulty and the number of rewards at risk. In particular, monkeys widened their cashout-response region as their accumulated rewards increased, providing more protection against a more costly error. These findings demonstrate a new continuity between humans' and animals' uncertainty systems. They reveal a calibration by macaques of present risk to trial difficulty tolerated. They show that animals' uncertainty-monitoring and risk-management systems have substantial trial-by-trial flexibility.

  8. Behavioural and pharmacokinetic studies in the monkey (Macaca mulatta) with diazepam, nordiazepam and related 1,4-benzodiazepines.

    Science.gov (United States)

    Curry, S H; Whelpton, R; Nicholson, A N; Wright, C M

    1977-11-01

    1. Behavioural activity (delayed differentiation and spatial delayed alternation) and pharmacokinetics of diazepam and its metabolites, N-desmethyldiazepam (nordiazepam), 3-hydroxydiazepam (temazepam) and 3-hydroxy-N-desmethyldiazepam (oxazepam), and of dipotassium clorazepate (clorazepate), were studied in the monkey (Macaca mulatta). Diazepam and its metabolites (1.8 and 3.0 mg/kg) and clorazepate (2.6 and 4.3 mg/kg) were given by intraperitoneal injection. 2. Hydroxylation of diazepam (temazepam and oxazepam) led to a loss of, or a considerable reduction in, behavioural activity, whereas activity was preserved, though modified, by demethylation (nordiazepam). It was not possible to establish change in behaviour at specific time intervals after clorazepate, but combined performance data revealed an effect. 3. The maximum mean plasma concentrations of diazepam, temazepam, oxazepam and clorazepate were observed at 0.5 h, and the maximum mean plasma concentration of nordiazepam was observed at 1 hour. Plasma concentrations of nordiazepam were the highest and decreased monoexponentially. Plasma concenqrations of the other drugs declined rapidly at first but more slowly later, and these data were analysed as biexponential models. In the analysis for metabolites, nordiazepam reached measurable levels after the injection of diazepam and clorazepate. 4. It is suggested that differences in the effects of closely related benzodiazepines may not be due solely to their plasma pharmacokinetic properties, but may arise from differences in their intrinsic activity.

  9. Rhesus monkeys (Macaca mulatta) discriminate between knowing and not knowing and collect information as needed before acting.

    Science.gov (United States)

    Hampton, Robert R; Zivin, Aaron; Murray, Elisabeth A

    2004-10-01

    Humans use memory awareness to determine whether relevant knowledge is available before acting, as when we determine whether we know a phone number before dialing. Such metacognition, or thinking about thinking, can improve selection of appropriate behavior. We investigated whether rhesus monkeys ( Macaca mulatta) are capable of a simple form of metacognitive access to the contents of short-term memory. Monkeys chose among four opaque tubes, one of which concealed food. The tube containing the reward varied randomly from trial to trial. On half the trials the monkeys observed the experimenter baiting the tube, whereas on the remaining trials their view of the baiting was blocked. On each trial, monkeys were allowed a single chance to select the tube containing the reward. During the choice period the monkeys had the opportunity to look down the length of each tube, to determine if it contained food. When they knew the location of the reward, most monkeys chose without looking. In contrast, when ignorant, monkeys often made the effort required to look, thereby learning the location of the reward before choosing. Looking improved accuracy on trials on which monkeys had not observed the baiting. The difference in looking behavior between trials on which the monkeys knew, and trials on which they were ignorant, suggests that rhesus monkeys discriminate between knowing and not knowing. This result extends similar observations made of children and apes to a species of Old World monkey, suggesting that the underlying cognitive capacities may be widely distributed among primates.

  10. Generalization hypothesis of abstract-concept learning: learning strategies and related issues in Macaca mulatta, Cebus apella, and Columba livia.

    Science.gov (United States)

    Wright, Anthony A; Katz, Jeffrey S

    2007-11-01

    The generalization hypothesis of abstract-concept learning was tested with a meta-analysis of rhesus monkeys (Macaca mulatta), capuchin monkeys (Cebus apella), and pigeons (Columba livia) learning a same/different (S/D) task with expanding training sets. The generalization hypothesis states that as the number of training items increases, generalization from the training pairs will increase and could explain the subjects' accurate novel-stimulus transfer. By contrast, concept learning is learning the relationship between each pair of items; with more training items subjects learn more exemplars of the rule and transfer better. Having to learn the stimulus pairs (the generalization hypothesis) would require more training as the set size increases, whereas learning the concept might require less training because subjects would be learning an abstract rule. The results strongly support concept or rule learning despite severely relaxing the generalization-hypothesis parameters. Thus, generalization was not a factor in the transfer from these experiments, adding to the evidence that these subjects were learning the S/D abstract concept.

  11. Effect of gonadotropin-releasing hormone antagonist on primordial follicle survival in the primate ovary.

    Science.gov (United States)

    Attaman, Jill; Arbogast, Laura K; Friedman, Chad I; Danforth, Douglas R

    2014-01-01

    To examine the effects of gonadotropin-releasing hormone (GnRH) antagonist on primordial follicle reserve in the primate ovary. A prospective basic research study in which 10 juvenile cynomolgus monkeys (Macaca fascicularis) had 1 ovary surgically removed. Six animals were then treated with the GnRH antagonist antide (1.0 mg/kg/day) for 14 days, and 4 animals were treated with vehicle. After treatment the contralateral ovary was removed and both ovaries were prepared for assessment of primordial, primary, and secondary follicle numbers. Antide treatment resulted in a modest (13%) but significant decrease in primordial follicle number in juvenile macaques (p = 0.048, n = 6). Three animals demonstrated a marked reduction in primordial follicles (19%, 25%, 36%) and 3 animals had no (primordial follicles after antide treatment. Control animals demonstrated no change in primordial follicle number following vehicle treatment. Antide had no effect on primary, secondary, or early antral follicle numbers and did not affect circulating estradiol concentrations. In contrast to mice, in which GnRH antagonist treatment markedly reduces primordial follicle reserve, the effect of antide in nonhuman primates was less dramatic and somewhat variable. These data suggest there may be a subset of animals susceptible to the adverse effects of GnRH antagonist on primordial follicle survival.

  12. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Anna de Lang

    2007-08-01

    Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

  13. Studies on the effect of 4-methylpyrazole on methanol poisoning using the monkey as an animal model: with particular reference to the ocular toxicity.

    Science.gov (United States)

    Blomstrand, R; Ingemansson, S O

    1984-07-01

    Young cynomolgus monkeys (Macaca fascicularis) were chosen as a model to investigate the ocular toxicity in animals poisoned with methanol and treated with 4-methylpyrazole (4-MP). The metabolism of methanol in the monkey was investigated after administration of 4-MP. Plasma levels of methanol, formic acid, 4-MP and 4-hydroxy-MP (4-OH-MP) were determined. After intramuscular injection, 4-MP was rapidly absorbed and depressed the elimination rate of methanol as well as the accumulation of formate in the blood. The results show the same great individual variations in monkeys as in humans regarding the susceptibility to methanol poisoning. Administration of a single dose of 5 g/kg induces a serious intoxication in most monkeys, causing death to some of them. Two monkeys receiving a single dose of 6 g/kg of methanol developed a serious initial inebriation and were treated with 4-MP. These monkeys survived and showed no signs of toxicity on ocular examinations which included ophtalmoscopy and electroretinogram (ERG) recordings.

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

    Directory of Open Access Journals (Sweden)

    Alexander Strom

    Full Text Available Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE-infected female cynomolgus monkeys (Macaca fascicularis. The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c. infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001 which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  15. Quantitation and localization of regional body fat distribution--a comparison between magnetic resonance imaging and somatometry.

    Science.gov (United States)

    Sharma, R C; Kramsch, D M; Lee, P L; Colletti, P; Jiao, Q

    1996-03-01

    The emerging concept that various fat compartments are metabolically active and play separate and decisive roles in the pathogenesis of coronary atherosclerosis, hypertension, insulin resistance, diabetes and stroke, has given obesity research a new direction. Of particular interest is the relative amount of intra-abdominal fat thought to be responsible for the metabolic complications. We studied the precise fat distribution and its correlations with the metabolic parameters in 44 non-human primates (Macaca fascicularis). Intra-abdominal, subcutaneous, and total abdominal fat (IAF, SAF, TAF) were assessed by magnetic resonance imaging (MRI) and somatometry. Quantitative computer analyses of abdominal MRI scans revealed predominant IAF distribution. Box plot analysis of IAF and SAF revealed wide diversity in the amounts of fat, especially in monkeys with body mass index (BMI) < 30 kg/m2. Primates with similar BMI in each quartile revealed an extensive heterogeneity in IAF as well as SAF. Numerous significant correlations within site-specific somatometric measurements as well as within the MRI determinants of abdominal fat were seen. However, only body weight correlated with IAF and skinfolds could predict SAF. After adjusting for body weight, partial correlation analysis showed a significant correlation (P < 0.05) between total cholesterol and IAF. MRI revealed considerable heterogeneity of IAF, SAF and TAF in cohort of primates believed to be homogeneous by somatometric definition. Male cynomolgus monkeys appear to be a valuable model for a systematic evaluation of fat. Individuals with identical body weight and height may show a diverse pattern of fat distribution.

  16. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Holland, G.N.; O' Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

    1988-06-01

    To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease.

  17. Squirrel monkeys (Saimiri sciureus) infected with the agent of bovine spongiform encephalopathy develop tau pathology.

    Science.gov (United States)

    Piccardo, P; Cervenak, J; Yakovleva, O; Gregori, L; Pomeroy, K; Cook, A; Muhammad, F S; Seuberlich, T; Cervenakova, L; Asher, D M

    2012-07-01

    Squirrel monkeys (Saimiri sciureus) were infected experimentally with the agent of classical bovine spongiform encephalopathy (BSE). Two to four years later, six of the monkeys developed alterations in interactive behaviour and cognition and other neurological signs typical of transmissible spongiform encephalopathy (TSE). At necropsy examination, the brains from all of the monkeys showed pathological changes similar to those described in variant Creutzfeldt-Jakob disease (vCJD) of man, except that the squirrel monkey brains contained no PrP-amyloid plaques typical of that disease. Constant neuropathological features included spongiform degeneration, gliosis, deposition of abnormal prion protein (PrP(TSE)) and many deposits of abnormally phosphorylated tau protein (p-Tau) in several areas of the cerebrum and cerebellum. Western blots showed large amounts of proteinase K-resistant prion protein in the central nervous system. The striking absence of PrP plaques (prominent in brains of cynomolgus macaques [Macaca fascicularis] with experimentally-induced BSE and vCJD and in human patients with vCJD) reinforces the conclusion that the host plays a major role in determining the neuropathology of TSEs. Results of this study suggest that p-Tau, found in the brains of all BSE-infected monkeys, might play a role in the pathogenesis of TSEs. Whether p-Tau contributes to development of disease or appears as a secondary change late in the course of illness remains to be determined.

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

    Science.gov (United States)

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

    2014-01-01

    Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  19. 太行山猕猴掌面肤纹三角分布%Distribution of the triradius on the palms in Taihang Macaca mulatta

    Institute of Scientific and Technical Information of China (English)

    赵晓进; 范红军; 靳想

    2012-01-01

    Objective:To report the characteristic of the triradius on the palms in the Taihang Macaca mulatto.. Methods: The sample comprised 31 individuals (8 males and 23 females) whose dermatoglyphics were completed and clear. The triradii on palms were taken with a digital camera or direct observation. Results : There constantly existed ten triradii on the palms in Macaca mulatto , and the average number of the triradius was 9. 1, and they ranged from 8 to 11. Conclusion: There is a significant difference in the position of palmar triradii between Macaca mulatto and other primates. Sex difference and bi-manual difference were not significant. The difference is mainly due to the evolution degree of primates, the development of palmar pad, the dermatoglyphic patterns and the printing procedure.%目的:了解太行山猕猴掌面三角的分布特征.方法:直接观察太行山猕猴掌面肤纹标本31例.结果:太行山猕猴掌面三角常出现的三角有10个,三角数目在8~11个之间,平均9.1个.结论:太行山猕猴掌面三角分布模式与其他灵长类掌面三角相比有差异.掌面三角性差和侧差无差异.造成这些差异的主要原因与灵长类动物进化程度、掌垫发育、花纹类型以及观察方法有关.

  20. Drug-induced expansion and differentiation of V gamma 9V delta 2 T cells in vivo: the role of exogenous IL-2.

    Science.gov (United States)

    Casetti, Rita; Perretta, Gemma; Taglioni, Alessandra; Mattei, Maurizio; Colizzi, Vittorio; Dieli, Francesco; D'Offizi, Gianpiero; Malkovsky, Miroslav; Poccia, Fabrizio

    2005-08-01

    Human Vgamma9Vdelta2 T cells recognize nonpeptidic Ags generated by the 1-deoxy-d-xylulose 5-phosphate (many eubacteria, algae, plants, and Apicomplexa) and mevalonate (eukaryotes, archaebacteria, and certain eubacteria) pathways of isoprenoid synthesis. The potent Vgamma9Vdelta2 T cell reactivity 1) against certain cancer cells or 2) induced by infectious agents indicates that therapeutic augmentations of Vgamma9Vdelta2 T cell activities may be clinically beneficial. The functional characteristics of Vgamma9Vdelta2 T cells from Macaca fascicularis (cynomolgus monkey) are very similar to those from Homo sapiens. We have found that the i.v. administration of nitrogen-containing bisphosphonate or pyrophosphomonoester drugs into cynomolgus monkeys combined with s.c. low-dose (6 x 10(5) U/animal) IL-2 induces a large pool of CD27+ and CD27- effector/memory T cells in the peripheral blood of treated animals. The administration of these drugs in the absence of IL-2 is substantially less effective, indicating the importance of additional exogenous costimuli. Shortly after the costimulatory IL-2 treatment, only gammadelta (but not alphabeta) T cells expressed the CD69 activation marker, indicating that Vgamma9Vdelta2 T lymphocytes are more responsive to low-dose IL-2 than alphabeta T cells. Up to 100-fold increases in the numbers of peripheral blood Vgamma9Vdelta2 T cells were observed in animals receiving the gammadelta stimulatory drug plus IL-2. Moreover, the expanded Vgamma9Vdelta2 T cells were potent Th1 effectors capable of releasing large amounts of IFN-gamma. These results may be relevant for designing novel (or modifying current) immunotherapeutic trials with nitrogen-containing bisphosphonate or pyrophosphomonoester drugs.

  1. 猕猴脱毛的营养学因素分析%Analysis on the Nutriology Parameters of Shed in Macaca mulatta

    Institute of Scientific and Technical Information of China (English)

    鲁帅尧; 和占龙; 陈丽雄; 赵远; 禹文海; 王俊斌; 杨凤梅

    2011-01-01

    Objective To improve and prevent shed of Macaca mulatta by comparison and analysis the nutriology parameters. Methods Macaca mulatta was divided into A, B and C group according to condition of their hair. Hair and serum were collected to determine trace elements, amino acid and mineral in serum. Results The content of Mn, Zn, Pb and As in hair show extremely significant difference (P <0. 01 ), but no significant change in the content of Cu and Fe (P >0. 05). The content of Pro, Val, NH3, Arg, Tyr, Gystine, Phe, Lys, His and total amino acids in hair show extremely significant difference (P <0. 01 ). The content of trace element in serum was no big change, except Mg, P, Cu and Ca in A and B groups were higher than C group. Conclusion The quantity of Mn and Zn in addition maybe the reason caused Macaca mulatta shed. Gystine may improve and enhance the hair quantity; Ca, Mg, P and Cu possibly can affect the hair quantity in artificial raising Macaca mulatta when fed in high nutritional level.%目的 通过对猕猴脱毛的相关营养学指标的比较分析,为改善人工饲养猕猴脱毛状况及其防治提供参考数据.方法 根据被毛状况分组A、B、C,采集试验猴被毛和血清,测定其微量元素和氨基酸以及血清矿物元素,对各组相应指标进行比较分析.结果 各组试验猴被毛Cu、Fe含量无显著性差异(P>0.05),但Mn、Zn、Pb、As则均有极显著性差异(P0.05).A、B组的血清Mg、P、Cu和Ca的含量高于C组,其余矿物元素的含量基本一致.结论 Mn过量、Zn的供给不足可能是影响人工饲养猕猴被毛质量的因素;胱氨酸对改善猕猴被毛品质、提高被毛质量应该有一定作用;高营养水平的Ca、Mg、P和Cu可能会影响人工饲养的猕猴的被毛质量.

  2. Identification of putative substrates for cynomolgus monkey cytochrome P450 2C8 by substrate depletion assays with 22 human P450 substrates and inhibitors.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2016-07-01

    Cynomolgus monkeys are widely used in drug developmental stages as non-human primate models. Previous studies used 89 compounds to investigate species differences associated with cytochrome P450 (P450 or CYP) function that reported monkey specific CYP2C76 cleared 19 chemicals, and homologous CYP2C9 and CYP2C19 metabolized 17 and 30 human CYP2C9 and/or CYP2C19 substrates/inhibitors, respectively. In the present study, 22 compounds selected from viewpoints of global drug interaction guidances and guidelines were further evaluated to seek potential substrates for monkey CYP2C8, which is highly homologous to human CYP2C8 (92%). Amodiaquine, montelukast, quercetin and rosiglitazone, known as substrates or competitive inhibitors of human CYP2C8, were metabolically depleted by recombinant monkey CYP2C8 at relatively high rates. Taken together with our reported findings of the slow eliminations of amodiaquine and montelukast by monkey CYP2C9, CYP2C19 and CYP2C76, the present results suggest that these at least four chemicals may be good marker substrates for monkey CYP2C8. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Birth origin differentially affects depressive-like behaviours: are captive-born cynomolgus monkeys more vulnerable to depression than their wild-born counterparts?

    Directory of Open Access Journals (Sweden)

    Sandrine M J Camus

    Full Text Available BACKGROUND: Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. METHODS: The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. RESULTS: We identified 10 distinct profiles (groups A to J that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. CONCLUSIONS: Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.

  4. Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34(+) bone marrow cells, following gamma irradiation in cynomolgus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [CEA, DSV, Serv Immunovirol, Inst Maladies Emergentes et Therapies Innovantes, Fontenay Aux Roses (France); Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [Univ Paris 11, UMR E01, Orsay (France); Negre, D.; Cosset, F. [Univ Lyon, UCB Lyon 1, IFR 128, F-69007 Lyon (France); Negre, D.; Cosset, F. [INSERM, U758, F-69007 Lyon (France); Negre, D.; Cosset, F.L. [Ecole NormaleSuper Lyon, F-69007 Lyon (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Lab Radiobiol, F-78352 Jouy En Josas (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Etude Genome, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Radiobiol Lab, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Etude Genome, F-78352 Jouy En Josas (France)

    2008-07-01

    Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myelo-ablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34{sup +} bone marrow cells following gamma irradiation in cynomolgus macaques. The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% {+-} 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudo-typed and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% {+-} 10%). A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producing eGFP were detected as early as three days after transplantation,and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion: The transplantation of CD34{sup +} bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T-and B-lymphocyte, thrombocyte and red blood cell compartments. (authors)

  5. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load.

    Directory of Open Access Journals (Sweden)

    Collin R Diedrich

    Full Text Available HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb infection are at significantly greater risk of reactivation tuberculosis (TB than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV. Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection.

  6. Prophylactic orthosteric inhibition of leukocyte integrin CD11b/CD18 prevents long-term fibrotic kidney failure in cynomolgus monkeys

    Science.gov (United States)

    Dehnadi, Abbas; Benedict Cosimi, A.; Neal Smith, Rex; Li, Xiangen; Alonso, José L.; Means, Terry K.; Arnaout, M. Amin

    2017-01-01

    Ischaemic acute kidney injury (AKI), an inflammatory disease process, often progresses to chronic kidney disease (CKD), with no available effective prophylaxis. This is in part due to lack of clinically relevant CKD models in non-human primates. Here we demonstrate that inhibition of the archetypal innate immune receptor CD11b/CD18 prevents progression of AKI to CKD in cynomolgus monkeys. Severe ischaemia-reperfusion injury of the right kidney, with subsequent periods of the left ureter ligation, causes irreversible right kidney failure 3, 6 or 9 months after AKI. Moreover, prophylactic inactivation of CD11b/CD18, using the orthosteric CD11b/CD18 inhibitor mAb107, improves microvascular perfusion and histopathology, reduces intrarenal pro-inflammatory mediators and salvages kidney function long term. These studies reveal an important early role of CD11b+ leukocytes in post-ischaemic kidney fibrosis and failure, and suggest a potential early therapeutic intervention to mitigate progression of ischaemic AKI to CKD in humans. PMID:28071653

  7. Birth Origin Differentially Affects Depressive-Like Behaviours: Are Captive-Born Cynomolgus Monkeys More Vulnerable to Depression than Their Wild-Born Counterparts?

    Science.gov (United States)

    Camus, Sandrine MJ.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

    2013-01-01

    Background Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder) in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. Methods The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. Results We identified 10 distinct profiles (groups A to J) that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J) present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. Conclusions Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups. PMID:23861787

  8. Subchronic safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis stimulating agent, after 5-week subcutaneous injection in Cynomolgus monkeys and Sprague-Dawley rats.

    Science.gov (United States)

    Gong, Xue-Lian; Zhang, Xiao-Dong; Li, Juan; Zhang, Xiao-Fang; Zong, Ying; Lu, Guo-Cai; Yuan, Bo-Jun

    2013-10-01

    EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is coupled to polyethylene glycol (PEG) and designed to specifically bind and activate the erythropoietin (EPO) receptor to result in production of red blood cells. This study was designed to evaluate the potential subchronic toxicity of EPO-018B for Cynomolgus monkeys and Sprague-Dawley rats both at 0, 0.5, 5 and 50 mg/kg every week for 5 weeks, followed by 6-week recovery for rats and 12-week recovery for monkeys. The No Observed Adverse Effect Level (NOAEL) for rats and monkeys were both considered to be at least 0.5 mg/kg/day, the minimum toxic dose to be 5.0 mg/kg/day and the severe toxic dose to be more than 50.0 mg/kg/day. The toxicological effects included the exaggerated pharmacology and secondary sequelae that resulted from an erythropoiesis-stimulating agent treatment to healthy animals. Most treatment induced effects were reversible or showed ongoing recovery upon discontinuation of treatment. The anticipated patient population for EPO-018B treatment is targeted to be the anemia patients caused by chronic renal failure or chemotherapy against to cancer and is expected to have an ideal clinical application prospect.

  9. Barusiban, a new highly potent and long-acting oxytocin antagonist: pharmacokinetic and pharmacodynamic comparison with atosiban in a cynomolgus monkey model of preterm labor.

    Science.gov (United States)

    Reinheimer, Torsten M; Bee, Walter H; Resendez, John C; Meyer, Julie K; Haluska, George J; Chellman, Gary J

    2005-04-01

    Preterm labor (PTL) represents a significant unmet clinical need that affects up to 20% of all pregnancies and is a leading cause of preterm delivery and associated neonatal morbidity and mortality. Therapeutic options are limited, with existing drug therapy (tocolytics) compromised by side effects and limited efficacy. Because oxytocin (OT) is likely to be involved causally in PTL, this study compared two OT receptor antagonists, barusiban and atosiban, for their tocolytic effects. OT was given to instrumented pregnant cynomolgus monkeys to induce contractions and simulate PTL. Barusiban or atosiban was then given iv (bolus or infusion) to evaluate inhibitory effects on uterine contractions, measured by telemetric recording of intrauterine pressure. Both antagonists had high efficacy (96-98% inhibition of intrauterine pressure) and rapid onset of action (0.5-1.5 h). Barusiban was three to four times more potent than atosiban, which was attributed to its higher affinity and selectivity for the OT receptor. Barusiban also had a much longer duration of action (>13-15 h, compared with 1-3 h for atosiban). The inhibitory effects of barusiban were reversible within 1.5-2.5 h by high-dose OT infusion. Overall, barusiban's improved potency, long duration of action, and reversibility may provide an improved tocolytic for treatment of PTL.

  10. Daily application of alprostadil topical cream (Vitaros) does not impact vaginal pH, flora, or histology in female cynomolgus monkeys.

    Science.gov (United States)

    Meier-Davis, Susan R; Debar, Salma; Siddoway, Jacob; Rabe, Mark

    2015-01-01

    Topical alprostadil cream (Vitaros) is approved in Canada and Europe for the treatment of erectile dysfunction. To determine the effects on the female urogenital tract with repeated administration of the entire dose (300 μg alprostadil containing 2.5% dodecyl-2-n,n-dimethylaminopropionate hydrochloride), the vaginal pH, flora, and histology were assessed as a model for 100% transference from male to the female during unprotected sexual intercourse. Female cynomolgus monkeys were administered the entire dose of Vitaros for 14 days with a 7-day recovery. Relative to vehicle and placebo cream, the vaginal pH and microflora were determined at baseline and weekly, thereafter. Vaginal biopsies were evaluated at the end of dosing and recovery. All animals were clinically normal for the study duration, and the vaginal pH was consistent between dose groups and the dosing period. Vaginal microflora and histopathology findings of mild inflammation were generally similar across treatment groups. In conclusion, repeated vaginal exposure to Vitaros did not alter the pH, microflora, or histology after 14 daily doses, supporting the safety of Vitaros transference to the female partner.

  11. Repeat-dose toxicology evaluation in cynomolgus monkeys of AVI-4658, a phosphorodiamidate morpholino oligomer (PMO) drug for the treatment of duchenne muscular dystrophy.

    Science.gov (United States)

    Sazani, Peter; Ness, Kirk P Van; Weller, Doreen L; Poage, Duane W; Palyada, Kiran; Shrewsbury, Stephen B

    2011-05-01

    AVI-4658 is a phosphorodiamidate morpholino oligomer (PMO) drug designed to restore dystrophin expression in a subset of patients with Duchenne muscular dystrophy (DMD). Previous reports demonstrated this clinical proof-of-principle in patients with DMD following intramuscular injection of AVI-4658. This preclinical study evaluated the toxicity and toxicokinetic profile of AVI-4658 when administered either intravenously (IV) or subcutaneously (SC) to cynomolgus monkeys once weekly over 12 weeks, at doses up to the maximum feasible dose of 320 mg/kg per injection. No drug-related effects were noted on survival, clinical observations, body weight, food consumption, opthalmoscopic or electrocardiographic evaluations, hematology, clinical chemistry, urinalysis, organ weights, and macroscopic evaluations. Drug-related microscopic renal effects were dose-dependent, apparently reversible, and included basophilic granules (minimal), basophilic tubules (minimal to moderate), and tubular vacuolation (minimal to mild). These data establish the tolerability of AVI-4658 at doses up to and including the maximum feasible dose of 320 mg/kg by IV bolus or SC injection.

  12. A heterologous DNA prime-Venezuelan equine encephalitis virus replicon particle boost dengue vaccine regimen affords complete protection from virus challenge in cynomolgus macaques.

    Science.gov (United States)

    Chen, Lan; Ewing, Dan; Subramanian, Hemavathy; Block, Karla; Rayner, Jonathan; Alterson, Kimberly D; Sedegah, Martha; Hayes, Curtis; Porter, Kevin; Raviprakash, Kanakatte

    2007-11-01

    A candidate vaccine (D1ME-VRP) expressing dengue virus type 1 premembrane and envelope proteins in a Venezuelan equine encephalitis (VEE) virus replicon particle (VRP) system was constructed and tested in conjunction with a plasmid DNA vaccine (D1ME-DNA) expressing identical dengue virus sequences. Cynomolgus macaques were vaccinated with three doses of DNA (DDD), three doses of VRP (VVV group), or a heterologous DNA prime-VRP boost regimen (DDV) using two doses of DNA vaccine and a third dose of VRP vaccine. Four weeks after the final immunization, the DDV group produced the highest dengue virus type 1-specific immunoglobulin G antibody responses and virus-neutralizing antibody titers. Moderate T-cell responses were demonstrated only in DDD- and DDV-vaccinated animals. When vaccinated animals were challenged with live virus, all vaccination regimens showed significant protection from viremia. DDV-immunized animals were completely protected from viremia (mean time of viremia = 0 days), whereas DDD- and VVV-vaccinated animals had mean times of viremia of 0.66 and 0.75 day, respectively, compared to 6.33 days for the control group of animals.

  13. Leveraging human genomic information to identify nonhuman primate sequences for expression array development

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    Boyle Nicholas F

    2005-11-01

    Full Text Available Abstract Background Nonhuman primates (NHPs are essential for biomedical research due to their similarities to humans. The utility of NHPs will be greatly increased by the application of genomics-based approaches such as gene expression profiling. Sequence information from the 3' end of genes is the key resource needed to create oligonucleotide expression arrays. Results We have developed the algorithms and procedures necessary to quickly acquire sequence information from the 3' end of nonhuman primate orthologs of human genes. To accomplish this, we identified terminal exons of over 15,000 human genes by aligning mRNA sequences with genomic sequence. We found the mean length of complete last exons to be approximately 1,400 bp, significantly longer than previous estimates. We designed primers to amplify genomic DNA, which included at least 300 bp of the terminal exon. We cloned and sequenced the PCR products representing over 5,500 Macaca mulatta (rhesus monkey orthologs of human genes. This sequence information has been used to select probes for rhesus gene expression profiling. We have also tested 10 sets of primers with genomic DNA from Macaca fascicularis (Cynomolgus monkey, Papio hamadryas (Baboon, and Chlorocebus aethiops (African green monkey, vervet. The results indicate that the primers developed for this study will be useful for acquiring sequence from the 3' end of genes for other nonhuman primate species. Conclusion This study demonstrates that human genomic DNA sequence can be leveraged to obtain sequence from the 3' end of NHP orthologs and that this sequence can then be used to generate NHP oligonucleotide microarrays. Affymetrix and Agilent used sequences obtained with this approach in the design of their rhesus macaque oligonucleotide microarrays.

  14. A Comparison of the Pathogenesis of Marburg Virus Disease in Humans and Nonhuman Primates and Evaluation of the Suitability of These Animal Models for Predicting Clinical Efficacy under the 'Animal Rule'.

    Science.gov (United States)

    Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

    2015-06-01

    Marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. In addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. Healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as Marburg virus in order to test the efficacy of a therapy or preventive prior to licensure. When human efficacy studies are neither ethical nor feasible, the US Food and Drug Administration may grant marketing approval of a drug or biologic product under the 'Animal Rule,' through which demonstration of the efficacy of a product can be 'based on adequate and well-controlled animal efficacy studies when the results of those studies establish that the drug is reasonably likely to produce clinical benefit in humans.' This process requires that the pathogenic determinants of the disease in the animal model are similar to those that have been identified in humans. After reviewing primarily English-language, peer-reviewed journal articles, we here summarize the clinical manifestations of Marburg virus disease and the results of studies in NHP showing the characteristics and progression of the disease. We also include a detailed comparison of the characteristics of the human disease relative to those for NHP. This review reveals that the disease characteristics of Marburg virus disease are generally similar for humans and 3 NHP species: cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and African green monkeys (Chlorocebus aethiops).

  15. Early involvement in friendships predicts later plasma concentrations of oxytocin and vasopressin in juvenile rhesus macaques (Macaca mulatta

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    Tamara Aliza Rachel Weinstein

    2014-08-01

    Full Text Available The neuropeptides oxytocin (OT and vasopressin (AVP are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques’ (Macaca mulatta friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center. Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay. Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject, multiplex friendships (friendships displayed in more than one behavioral domain, and total number of friendships. Females’ number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males’ plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual’s psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in

  16. High-fat diet combined with low-dose streptozotocin injections induces metabolic syndrome in Macaca mulatta.

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    Li, Linzhao; Liao, Guangneng; Yang, Guang; Lu, Yanrong; Du, Xiaojiong; Liu, Jingping; Li, Lan; Wang, Chengshi; Li, Li; Ren, Yan; Zhong, Zhihui; Cheng, Jingqiu; Chen, Younan

    2015-08-01

    Metabolic syndrome (MetS) is associated with abdominal obesity, hyperlipidemia, insulin resistance, and type 2 diabetes mellitus, and increases the risk of cardiovascular disease. Given the complex multifactorial pathogenesis of MetS, qualified animal models are currently seriously limited for researchers. The aim of our study was to develop a MetS model in juvenile rhesus monkeys (Macaca mulatta). Rhesus monkeys (1-year-old) fed a high-fat diet (15 % fat, 2 % cholesterol) were used as the HF group (n = 6), and those on a normal diet (5 % fat) were used as the control group (n = 4). After being fed a high-fat diet for approximately 12 months, 2 monkeys (HF + STZ group) were injected with low-dose streptozotocin (STZ, 25 mg/kg) twice, with a 7 days interval, and were then fed the same diet continuously for another 24 months. After 36 months of treatment, the high-fat diet monkeys, including the HF and HF + STZ groups, had acquired increased body weights, abnormal serum lipids, and impaired glucose tolerance compared to the control group. In addition, much more marked metabolic changes were observed in the two monkeys of the HF + STZ group, particularly in terms of high-blood glucose level and insulin resistance. Morphological observation of biopsies of liver and pancreatic tissues showed decreased islet number and mass and decreased insulin staining in the monkeys of the HF + STZ group. In addition, Oil red O staining suggested remarkable accumulation of lipid droplets in the hepatocytes. Our study suggested that a long-term high-fat diet followed with a low-dose STZ was able to induce MetS in juvenile rhesus monkeys with faster pathophysiological progress compared with high-fat diet induction alone. Our primary data showed that this method may have potentials to develop MetS animal model in non-human primates.

  17. Response of Rhesus Macaques (Macaca mulatta) to the Body of a Group Member That Died from a Fatal Attack

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    Buhl, Jacqueline S.; Aure, Bonn; Ruiz-Lambides, Angelina; Gonzalez-Martinez, Janis; Platt, Michael L.; Brent, Lauren J. N.

    2013-01-01

    Among animals that form social bonds, the death of a conspecific may be a significant social event, representing the loss of an ally and resulting in disruptions to the dominance hierarchy. Despite this potential biological importance, we have only limited knowledge of animals' reactions to the death of a group member. This is particularly true of responses to dead adults, as most reports describe the responses of mothers to dead infants. Here, we describe in detail and provide video evidence of the behavioral responses of a group of free-ranging rhesus macaques (Macaca mulatta) immediately after the death of a mid-ranking adult male as a result of a fatal attack. High-ranking male members of the group, suspected to have carried out the attack, dragged and bit the dead body, exhibiting a rate of aggression 20 times greater than baseline levels. Lower-ranking individuals approached and inspected the body by looking closely, smelling, and grooming the fur. There was inconclusive evidence that these rhesus macaques found the death of a conspecific stressful: Levels of grooming between group members after the fatal attack were significantly higher than baseline levels, and higher than levels of grooming after nonfatal attacks. However, when grooming levels were adjusted based on the assumption that individuals positioned close to the body, i.e., those visible to researchers, were more likely to be engaged in grooming than those positioned farther away, this difference from baseline was no longer significant. The rate of self-directed behaviors after the fatal attack was also not different from baseline. Many of the behaviors we observed directed toward the body (aggression, inspection) have been previously reported in chimpanzees and geladas, and are similar to reactions sometimes displayed by humans. As such, this report represents a potentially valuable contribution the nascent field of nonhuman primate thanatology. PMID:23459587

  18. Endozoochorous seed dispersal by Japanese macaques (Macaca fuscata): Effects of temporal variation in ranging and seed characteristics on seed shadows.

    Science.gov (United States)

    Tsuji, Yamato; Morimoto, Mayumi

    2016-02-01

    Variation in seed shadows generated by frugivores is caused by daily, seasonal, and inter-annual variation in ranging, as well as inter-specific variability in gut passage times according to seed characteristics. We studied the extent to which seed weight, specific gravity, and daily (morning, afternoon, and evening) and inter-annual (2004 vs. 2005) variation in ranging affected seed shadows generated by wild Japanese macaques (Macaca fuscata) in northern Japan. The macaques ingested fleshy fruits of 11 species during the two year study period; Viburnum dilatatum (Caprifoliaceae: heavier seeds with higher specific gravity) and Rosa multiflora (Rosaceae: lighter seeds with lower specific gravity) were eaten frequently in both years. The travel distances of macaques after feeding on V. dilatatum and R. multiflora fruits were estimated by combining feeding locations and ranging patterns measured in the field with gut passage times of model seeds in captive animals. Median travel distances after fruit feeding were 431 (quantile range: 277-654) and 478 m (265-646), respectively, with a maximum of 1,261 m. Neither year nor time of day affected travel distances. The gut passage time of model V. dilatatum seeds was longer than that of model R. multiflora seed, but this did not affect dispersal distances. Seed shadows for both species over 2 years showed unimodal distribution (peak: 101-500 m) and more than 90%, 20%, and 3% of ingested seeds were estimated to be dispersed >100, >500, and >1000 m, respectively, the longest known distances among macaque species. R. multiflora seeds tended to be dispersed further in 2004 than 2005, but V. dilatatum seeds were not, implying that inter-annual variations in ranging pattern due to the distribution and abundance of nut fruiting could affect dispersal distance.

  19. Cloning and high level expression of the biologically active extracellular domain of Macaca mulatta CD40 in Pichia pastoris.

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    Zhu, Shengyun; Wan, Lin; Yang, Hao; Cheng, Jingqiu; Lu, Xiaofeng

    2016-03-01

    The CD40-mediated immune response contributes to a wide variety of chronic inflammatory diseases. CD40 antagonists have potential as novel therapies for immune disorders. However, the CD40 pathway has not been well characterized in the rhesus monkey Macaca mulatta, which is a valuable animal model for human immune disease. An 834 bp transcript was cloned from peripheral blood mononuclear cells (PBMCs) of rhesus monkey using specific primers designed according to the predicted sequence of M. mulatta CD40 (mmCD40) in GenBank. Sequence analysis demonstrated that mmCD40 is highly homologous to human CD40 (hCD40), with an amino acid sequence identity of 94%. Genes encoding the extracellular domain of mmCD40 and the Fc fragment of the hIgG1 were inserted into a pPIC9K plasmid to produce mmCD40Ig by Pichia pastoris. Approximately 15-20 mg of the mmCD40Ig protein with ∼90% purity could be recovered from 1 L of culture. The purified mmCD40Ig protein can form dimers and can specifically bind CD40L-positive cells. Additionally, the mmCD40Ig protein can bind hCD40L protein in phosphate buffered saline and form a stable combination in a size-exclusion chromatography assay using a Superdex 200 column. Moreover, mmCD40Ig is as efficient as M. mulatta CTLA4Ig (mmCTLA4Ig) to suppress Con A-stimulated lymphocyte proliferation. Additionally, mmCD40Ig only showed mild immunosuppressive activity in a one-way mixed lymphocyte reaction (MLR) system. These results suggest that mmCD40Ig secreted by P. pastoris was productive and functional, and it could be used as a tool for pathogenesis and therapies for chronic inflammatory diseases in a M. mulatta model.

  20. Comparison of Indoor Air Quality between 2 Ventilation Strategies in a Facility Housing Rhesus Macaques (Macaca mulatta).

    Science.gov (United States)

    Monts de Oca, Nicole A; Laughlin, Mitzi; Jenkins, John; Lockworth, Cynthia R; Bolton, Iris D; Brammer, David W

    2015-09-01

    Adequate indoor-air quality (IAQ)--defined by the temperature, relative humidity, and the levels of carbon dioxide, small particles, and total volatile organic compounds (TVOC)--is crucial in laboratory animal facilities. The ventilation standards for controlling these parameters are not well defined. This study assessed the effect of 2 ventilation strategies on IAQ in 2 rooms housing rhesus macaques (Macaca mulatta). We hypothesized that using a demand-controlled ventilation (DCV) system with a baseline ventilation rate of less than 3 fresh-air changes per hour (ACH) would maintain IAQ comparable to or better than the traditional constant flow rate (CFR) system at 12 fresh ACH. During a 60-d study period, each of the 2 rooms operated 30 d on DCV and 30 d on CFR ventilation. In both rooms, temperatures remained more consistently within the established setpoint during the DCV phase than during the CFR phase. Relative humidity did not differ significantly between rooms or strategies. CO₂ was lower during the CFR phase than DCV phase. Small-particle and TVOC levels were lower during CFR in the larger (3060 ft(3)) room but not the smaller (2340 ft(3)) room. During the DCV phase, the larger room was at the baseline airflow rate over 99% of the time and the smaller room over 96% of the time. The DCV strategy resulted in a baseline airflow rate of less than 3 ACH, which in turn provided acceptable IAQ over 96% of the time; higher ventilation rates were warranted only during sanitation periods.

  1. A comparative of G-banded chromosome of Assam Macaque (Macaca assamensis and relationship to human (Homo sapiens

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    Bunjongrat, R.

    2006-05-01

    Full Text Available This research was the first to report a comparative analysis of G-banded chromosome of Assam macaque, Macaca assamensis (Primate, Cercopithecidae and relationship to human, Homo sapiens (Primate, Hominidae. Blood samples were taken from two males and two females held captive in Nakhonratchasima Zoo and Songkla Zoo. After the standard whole blood lymphocyte culture at 37ºC for 72 hr in presence of colchicine, metaphase spreads were performed on microscopic slides and air-dried. G-banding technique was applied to stain the chromosomes. The results showed that the number of diploid chromosomes of Assam macaque was 2n = 42. The type of autosomes are 18 metacentric and 22 submetacentric chromosomes. In addition, a pair of short arm chromosome 13 showed clearly observable satellite chromosome. X-chromosome was the submetacentric and Y chromosome was the smallest telocentric chromosome. We found that chromosome 5, 12, 13, 19 and X had the same G-banding patterns as those of human chromosomes. The short arm of chromosome 13 is similar to the chromosome 22 of human as indicated by G-banding techniques. In addition, the long arm of chromosome 13 is similar to the chromosome 15 of human. These results indicate that the chromosome 13 of the Assam macaque was split into 2 chromosomes. Chromosome 1, 3, 6, 7, 8, 9, 10, 11, 14, 17 and 20 are similar to those of human chromosomes. This study suggest that the chromosome 1 is a pericentric inversion of human chromosome 1. Chromosomes 2, 4, 15, 16, 18 and Y are different from those of human chromosomes. These results show the evolutionary relationship between the Assam macaque and human.

  2. Ordered recall in rhesus macaques (Macaca mulatta: Can monkeys recall the correct order of sequentially presented images?

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    Heather E O'Neil

    2006-01-01

    Full Text Available Previous research has demonstrated that rhesus monkeys (Macaca mulatta are capable of identifying sequentially shown images in any order among distractors (i.e. images not part of the list sequence. We investigated ordered recall in rhesus monkeys in which subjects were expected to recognize the correct order of images during a “test” phase (simultaneous presentation of images after they had seen the images presented sequentially in a “presentation” phase (sequential presentation of images. If subjects were successfully able to execute the ordered recall task, the first trial accuracy data would appear close to 100% accuracy and it would only take one day to learn the list since the lists used were short, 3-item lists. While this study did not conclusively demonstrate monkeys are capable of ordered recall of sequentially presented, trial unique images (i.e. a list sequence presented only once per session, the data suggests that when the stimuli are not trial unique the monkeys treat each sequence as a simultaneous chaining task. A simultaneous chaining paradigm entails simultaneous presentation of all items without any previous sequential presentation of the images. It is unclear whether results resembling simultaneous chaining are seen because these animals have previous experience with simultaneous chaining, if the training procedure needs to be modified for the monkeys to understand the task, or if the task is beyond their cognitive abilities. Further research with serial learning will clarify this finding and also seek to prove whether rhesus monkeys are in fact capable of such ordered recall tasks.

  3. Nucleotide sequence of the BamHI repetitive sequence, including the HindIII fundamental unit, as a possible mobile element from the Japanese monkey Macaca fuscata.

    Science.gov (United States)

    Prassolov, V S; Kuchino, Y; Nemoto, K; Nishimura, S

    1986-01-01

    Clustered repeat units produced by BamHI digestion of genomic DNA from the Japanese monkey Macaca fuscata [JMr(BamHI)] were sequenced by dideoxy DNA sequencing. The nucleotide sequences of several individual repeats showed that the BamHI repeat contains the 170-bp HindIII element as an integral part, and that it has more than 90% homology with the HindIII repeat element [AGMr(HindIII)] found in the genomic DNA of the African green monkey. In the JMr(BamHI) repeat unit, the 170-bp HindIII element is flanked by a 6-bp inverted repeat, which is part of a 22-bp direct repeat. This latter repeat of 22-bp asymmetrically overlaps the border between the internal AGMr(HindIII)-like region and adjacent regions of the JMr(BamHI) repeat. A similar structural feature of the BamHI repeat unit has been found in the genomic DNA of the baboon, but not in that of the African green monkey. These results show clearly that the BamHI repeat of the modern Japanese monkey originated as a result of insertion of an AGMr(HindIII) element into a certain site(s) of the genomic DNA of an ancestor of the modern Japanese monkey before Macaca-Cercocebus divergence.

  4. Development of a PET radioligand for the central 5-HT{sub 1B} receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds

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    Andersson, Jan D., E-mail: j.d.andersson@ki.s [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Pierson, M. Edward [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Finnema, Sjoerd J.; Gulyas, Balazs [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Heys, Richard; Elmore, Charles S. [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Farde, Lars [AstraZeneca Pharmaceuticals, Neuroscience Clinical, SE-15185 Soedertaelje (Sweden); Halldin, Christer [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden)

    2011-02-15

    Introduction: The serotonin 1B (5-HT{sub 1B}) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT{sub 1B} receptor in the primate brain in vivo. Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [{sup 11}C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography. Results: In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/{mu}mol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [{sup 11}C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT{sub 1B} receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics. Conclusion: Candidate [{sup 11}C]6, i.e., [{sup 11}C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT{sub 1B} receptors and was nominated for further preclinical characterization and PET examination in human subjects.

  5. Proteomic basis of the antibody response to monkeypox virus infection examined in cynomolgus macaques and a comparison to human smallpox vaccination.

    Directory of Open Access Journals (Sweden)

    Sarah Keasey

    Full Text Available Monkeypox is a zoonotic viral disease that occurs primarily in Central and West Africa. A recent outbreak in the United States heightened public health concerns for susceptible human populations. Vaccinating with vaccinia virus to prevent smallpox is also effective for monkeypox due to a high degree of sequence conservation. Yet, the identity of antigens within the monkeypox virus proteome contributing to immune responses has not been described in detail. We compared antibody responses to monkeypox virus infection and human smallpox vaccination by using a protein microarray covering 92-95% (166-192 proteins of representative proteomes from monkeypox viral clades of Central and West Africa, including 92% coverage (250 proteins of the vaccinia virus proteome as a reference orthopox vaccine. All viral gene clones were verified by sequencing and purified recombinant proteins were used to construct the microarray. Serum IgG of cynomolgus macaques that recovered from monkeypox recognized at least 23 separate proteins within the orthopox proteome, while only 14 of these proteins were recognized by IgG from vaccinated humans. There were 12 of 14 antigens detected by sera of human vaccinees that were also recognized by IgG from convalescent macaques. The greatest level of IgG binding for macaques occurred with the structural proteins F13L and A33R, and the membrane scaffold protein D13L. Significant IgM responses directed towards A44R, F13L and A33R of monkeypox virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with pathogenic virus strains, while recovery from infection also involved humoral responses to antigens uniquely recognized within the monkeypox virus proteome.

  6. Promoted differentiation of cynomolgus monkey ES cells into hepatocyte-like cells by co-culture with mouse fetal liver-derived cells

    Institute of Scientific and Technical Information of China (English)

    Ko Saito; Masahide Yoshikawa; Yukiteru Ouji; Kei Moriya; Mariko Nishiofuku; Shigehiko Ueda; Noriko Hayashi; Shigeaki Ishizaka; Hiroshi Fukui

    2006-01-01

    AIM:To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes.METHODS:Mouse fetal liver-derived cells (MFLCs) were prepared as adherent cells from mouse embryos on embryonic d (ED) 14, after which undifferentiated cES cells were co-cultured with MFLCs. The induction of cES cells along a hepatic lineage was examined in MFLCassisted differentiation, spontaneous differentiation,and growth factors (GF) and chemicals-induced differentiations (GF-induced differentiation) using retinoic acid, leukemia inhibitory factor (LIF), FGF2, FGF4,hepatocyte growth factor (HGF), oncostatin M (OSM),and dexamethasone.RESULTS:The mRNA expression of α-fetoprotein,albumin (ALB), α-1-antitrypsin, and hepatocyte nuclear factor 4α was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation. The expression of cytochrome P450 7a1, a possible marker for embryonic endoderm-derived mature hepatocytes,was only observed in cES cells that had differentiated in a co-culture with MFLCs. Further, the disappearance of Oct3/4, a representative marker of an undifferentiated state, was noted in cells co-cultured with MFLCs, but not in those undergoing spontaneous or GF-induced differentiation. Tmmunocytochemical analysis revealed an increased ratio of ALS-immunopositive cells among cES cells co-cultured with MFLCs, while glycogen storage and urea synthesis were also demonstrated.CONCLUSION:MFLCs showed an ability to induce cES cells to differentiate toward hepatocytes. The co-culture system with MFLCs is a useful method for induction of hepatocyte-like cells from undifferentiated cES cells.

  7. In vivo safety and persistence of endoribonuclease gene-transduced CD4+ T cells in cynomolgus macaques for HIV-1 gene therapy model.

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    Hideto Chono

    Full Text Available BACKGROUND: MazF is an endoribonuclease encoded by Escherichia coli that specifically cleaves the ACA sequence of mRNA. In our previous report, conditional expression of MazF in the HIV-1 LTR rendered CD4+ T lymphocytes resistant to HIV-1 replication. In this study, we examined the in vivo safety and persistence of MazF-transduced cynomolgus macaque CD4+ T cells infused into autologous monkeys. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo persistence of the gene-modified CD4+ T cells in the peripheral blood was monitored for more than half a year using quantitative real-time PCR and flow cytometry, followed by experimental autopsy in order to examine the safety and distribution pattern of the infused cells in several organs. Although the levels of the MazF-transduced CD4+ T cells gradually decreased in the peripheral blood, they were clearly detected throughout the experimental period. Moreover, the infused cells were detected in the distal lymphoid tissues, such as several lymph nodes and the spleen. Histopathological analyses of tissues revealed that there were no lesions related to the infused gene modified cells. Antibodies against MazF were not detected. These data suggest the safety and the low immunogenicity of MazF-transduced CD4+ T cells. Finally, gene modified cells harvested from the monkey more than half a year post-infusion suppressed the replication of SHIV 89.6P. CONCLUSIONS/SIGNIFICANCE: The long-term persistence, safety and continuous HIV replication resistance of the mazF gene-modified CD4+ T cells in the non-human primate model suggests that autologous transplantation of mazF gene-modified cells is an attractive strategy for HIV gene therapy.

  8. 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

    2017-06-12

    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.

  9. Effects of denosumab, alendronate, or denosumab following alendronate on bone turnover, calcium homeostasis, bone mass and bone strength in ovariectomized cynomolgus monkeys.

    Science.gov (United States)

    Kostenuik, Paul J; Smith, Susan Y; Samadfam, Rana; Jolette, Jacquelin; Zhou, Lei; Ominsky, Michael S

    2015-04-01

    Postmenopausal osteoporosis is a chronic disease wherein increased bone remodeling reduces bone mass and bone strength. Antiresorptive agents including bisphosphonates are commonly used to mitigate bone loss and fracture risk. Osteoclast inhibition via denosumab (DMAb), a RANKL inhibitor, is a newer approach for reducing fracture risk in patients at increased risk for fracture. The safety of transitioning from bisphosphonate therapy (alendronate; ALN) to DMAb was examined in mature ovariectomized (OVX) cynomolgus monkeys (cynos). One day after OVX, cynos (7-10/group) were treated with vehicle (VEH, s.c.), ALN (50 μg/kg, i.v., twice monthly) or DMAb (25 mg/kg/month, s.c.) for 12 months. Other animals received VEH or ALN for 6 months and then transitioned to 6 months of DMAb. DMAb caused significantly greater reductions in serum CTx than ALN, and transition from ALN to DMAb caused further reductions relative to continued ALN. DMAb and ALN decreased serum calcium (Ca), and transition from ALN to DMAb resulted in a lesser decline in Ca relative to DMAb or to VEH-DMAb transition. Bone histomorphometry indicated significantly reduced trabecular and cortical remodeling with DMAb or ALN. Compared with ALN, DMAb caused greater reductions in osteoclast surface, eroded surface, cortical porosity and fluorochrome labeling, and transition from ALN to DMAb reduced these parameters relative to continued ALN. Bone mineral density increased in all active treatment groups relative to VEH controls. Destructive biomechanical testing revealed significantly greater vertebral strength in all three groups receiving DMAb, including those receiving DMAb after ALN, relative to VEH controls. Bone mass and strength remained highly correlated in all groups at all tested skeletal sites, consistent with normal bone quality. These data indicate that cynos transitioned from ALN to DMAb exhibited reduced bone resorption and cortical porosity, and increased BMD and bone strength, without

  10. Non-clinical safety evaluation of repeated intramuscular administration of the AS15 immunostimulant combined with various antigens in rabbits and cynomolgus monkeys.

    Science.gov (United States)

    Garçon, N; Silvano, J; Kuper, C F; Baudson, N; Gérard, C; Forster, R; Segal, L

    2016-02-01

    Combination of tumor antigens with immunostimulants is a promising approach in cancer immunotherapy. We assessed animal model toxicity of AS15 combined with various tumor antigens: WT1 (rabbits), or p501, dHER2 and recPRAME (cynomolgus monkeys), administered in seven or 20 dose regimens versus a saline control. Clinical and ophthalmological examinations, followed by extensive post-mortem pathological examinations, were performed on all animals. Blood hematology and biochemistry parameters were also assessed. Antigen-specific antibody titers were determined by enzyme-linked immunosorbent assay. Additional assessments in monkeys included electrocardiography and immunohistochemical evaluations of the p501 expression pattern. Transient increases in body temperature were observed 4 h or 24 h after injections of recPRAME + AS15 and dHER2 + AS15. Edema and erythema were observed up to 1 week after most injections of recPRAME + AS15 and all injections of dHER2 + AS15. No treatment-related effects were observed for electrocardiography parameters. Mean fibrinogen levels were significantly higher in all treated groups compared to controls, but no differences could be observed at the end of the treatment-free period. Transient but significant differences in biochemistry parameters were observed post-injection: lower albumin/globulin ratios (p501 + AS15), and higher bilirubin, urea and creatinine (dHER2 + AS15). Pathology examinations revealed significant increases in axillary lymph node mean weights (recPRAME + AS15) compared to controls. A 100% seroconversion rate was observed in all treated groups, but not in controls. p501 protein expression was observed in prostates of all monkeys from studies assessing p501 + AS15. These results suggest a favorable safety profile of the AS15-containing candidate vaccines, supporting the use of AS15 for clinical development of potential anticancer vaccines.

  11. Non-clinical safety evaluation of single and repeated intramuscular administrations of MAGE-A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys.

    Science.gov (United States)

    Destexhe, Eric; Grosdidier, Emilie; Baudson, Nathalie; Forster, Roy; Gerard, Catherine; Garçon, Nathalie; Segal, Lawrence

    2015-07-01

    The MAGE-A3 recombinant protein combined with AS15 immunostimulant (MAGE-A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non-clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE-A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE-A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post-injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3-month treatment-free period (2/5 per gender per group). Local and systemic reactions and MAGE-A3-specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post-mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post-injection), but returned to normal after 1-8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment-related macroscopic findings were recorded after the treatment-free period. MAGE-A3-specific antibody and T-cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE-A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys.

  12. 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.

  13. MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3 in cynomolgus macaques.

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    Nathalie Dereuddre-Bosquet

    Full Text Available In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP model of mucosal challenge with SHIV(162P3 after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control, the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50 of SHIV(162P3. All control animals were infected with a peak plasma viral load of 10(5-10(6 viral RNA (vRNA copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.

  14. Evaluation of the PhysioTel™ Digital M11 cardiovascular telemetry implant in socially housed cynomolgus monkeys up to 16weeks after surgery.

    Science.gov (United States)

    Andersen, Ninette K; Meyer, Olivier; Bradley, Alys; Dragsted, Nils; Lassen, Anders B; Sjögren, Ingrid; Larsen, Julie M; Harvey, Warren; Bator, Rastislav; Milne, Aileen

    2017-09-01

    The novel PhysioTel™ Digital M11 telemetry implant was evaluated in socially housed monkeys with respect to both safety pharmacological cardiovascular (arterial blood pressure (BP), heart rate (HR) and electrocardiogram (ECG)) and toxicological (clinical pathology and histopathology) endpoints. Telemetry and clinical pathology data were obtained repeatedly up to 16weeks after surgery in four female cynomolgus monkeys, followed by necropsy. Due to postsurgical complications, one spare animal was included and only toxicological endpoints from the affected (fifth animal) were reported. Continuous telemetry recordings were conducted at periods without dosing and after ascending doses of moxifloxacin (0, 10, 30, 100mg/kg) and L-NAME (0, 0.1, 1, 10mg/kg). Additionally, a retrospective power analysis was conducted based on baseline M11 implant data from 32 other animals. During periods without dosing, the cardiovascular endpoints were stable over time and within normal ranges. Moxifloxacin and L-NAME elicited the expected pharmacological responses with dose-dependent increase in QTca (8, 17, 22ms) and BP (mean BP: 12, 21, 34mmHg), respectively. Expected intravascular and tissue reactions were observed at the sites of the BP catheter and the transmitter. Signs of infection (localised to the transmitter implantation site with associated systemic effects) was noted in the fifth animal. No systemic pathologies were seen in any animals. Power analysis (80% power) indicated that the minimal differences which can be detected in a parallel group design (n=6) are 7mmHg (mean BP), 16bpm (HR), 12ms (QTca). The M11 implant provided stable, high quality ECG and BP data for a duration covering the length of sub-chronic repeated dose toxicity studies without important impact on toxicological endpoints. Adequate power in order to elucidate major treatment-related cardiovascular effects was demonstrated. However to avoid post-surgical complications the implantation procedures should be

  15. New {alpha}{sub 1}-adrenoceptor antagonists derived from the antipsychotic sertindole - carbon-11 labelling and pet examination of brain uptake in the cynomolgus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Balle, Thomas E-mail: tb@dfuni.dk; Halldin, Christer; Andersen, Linus; Hjorth Alifrangis, Lene; Badolo, Lassina; Gjervig Jensen, Klaus; Chou, Y.-W.; Andersen, Kim; Perregaard, Jens; Farde, Lars

    2004-04-01

    Central {alpha}{sub 1}-adrenergic receptors are potential targets for recently developed antipsychotic drugs. Two new 11C labeled potent and selective {alpha}{sub 1}-adrenoceptor antagonists, 1- [2- [4-[1-(4-fluorophenyl)-5-(2-[{sup 11}C]methyl-tetrazol-5-yl)-1H-indol-3-yl]-1- pipridinyl]ethyl]-imidazolidin-2-one ([{sup 11}C]2) and 1- [2- [4-[1-(4-fluorophenyl)-5-(1-[{sup 11}C]methyl-(1,2,3-triazol-4-yl) -1H-indol-3-yl]- 1-piperidinyl]ethyl]-imidazolidin-2-one ([{sup 11}C]3) were prepared and evaluated for imaging of central {alpha}{sub 1}-adrenergic receptors in the cynomolgus monkey brain. For both compounds, the total brain radioactivity was only about 0.6% of the radioactivity injected i.v. There was no evident binding in regions known to contain {alpha}{sub 1}-adrenoceptors. This observation suggests that the affinity of the radioligands in primates in vivo is not sufficient to provide a signal for specific binding that can be differentiated from the background. In addition, active efflux by P-glycoprotein may be responsible for the low total brain-uptake of the two radioligands. Both compounds showed a highly polarised and verapamile sensitive transport across monolayers of Caco-2 cells. The total brain-uptake of [{sup 3}H]2 was 6 times higher in mdr1a(-/-) knock-out mice lacking the gene encoding P-glycoprotein compared to wild type mice. Pretreatment of one monkey with Cyclosporin A (15 mg/kg) resulted in 40% higher brain uptake for [{sup 11}C]3 when compared with baseline. These observations support the view that efflux by P-glycoprotein can be of quantitative importance for the total brain-uptake of some PET radioligands.

  16. Uterine autologous transplantation in cynomolgus monkeys:a preliminary report of 6 case%食蟹猴自体子宫原位再植研究

    Institute of Scientific and Technical Information of China (English)

    王沂峰; 钟丽娟; 饶军华; 祝颖; 余萍; 陈高文; 蔡保塔; 章正广; 刘娜; 吕晓刚; 熊菊香

    2014-01-01

    目的:探讨雌性食蟹猴自体子宫原位再植的手术学方法和其可行性,并评估显微外科技术在子宫再植中的作用。方法2011年5月至2014年3月,将6只7~12岁育龄期雌性食蟹猴,行自体子宫原位再植术。具体方法:随机分为两组,每组3只,A组为非显微镜组,在肉眼直视下进行深部盆腔血管吻合操作;B组为显微镜辅助操作组,采用10倍放大镜显微外科技术辅助手术操作。比较两组食蟹猴内生殖系统解剖数据、手术时间、血管吻合成功率等指标。术后定期行腹部超声观察子宫大小、血供情况,术后3个月剖腹探查评估再植子宫组织学形态。结果 A组切取子宫及血管蒂所需时间平均123.7 min、平均血管吻合时间180.7 min、平均后台灌注时间35.0 min、平均总手术时间为393.7 min;B组切取子宫及血管蒂所需时间平均88.7 min、平均血管吻合时间147.3 min、平均后台灌注时间27.3 min、平均总手术时间320.0 min,与A组相比均显著缩短。 A组后台灌注时间平均35.0 min,B组后台灌注时间平均27.3 min,两组比较差异无统计学意义。两组术中均吻合12条血管,A组3只猴手术血管吻合成功4条,而B组3只猴手术血管吻合12条均成功,两组动脉吻合成功率差异有统计学意义(P<0.05),静脉吻合成功率差异无统计学意义(P>0.05)。 A组子宫再植手术成功1例,但术后4周子宫缺血坏死;B组子宫再植手术3例均成功,存活的2例食蟹猴中1例术后17 d恢复月经,另1例于术后第50天恢复月经,术后3个月剖腹探查2例再植的子宫均存活良好。结论食蟹猴自体子宫再植手术技术可行,显微外科技术辅助可显著提高动脉吻合成功率。%Objective To evaluate the surgical feasibility of uterine autologous transplantation in female cynomolgus monkeys and explore the effect of

  17. The sweetness-inducing effect of miraculin; behavioural and neurophysiological experiments in the rhesus monkey Macaca mulatta.

    Science.gov (United States)

    Brouwer, J N; Glaser, D; Hard Af Segerstad, C; Hellekant, G; Ninomiya, Y; Van der Wel, H

    1983-04-01

    1. The gustatory effects of miraculin, the sweetness-inducing protein from the miracle fruit Synsepalum dulcificum, was studied in the rhesus monkey, Macaca mulatta.2. The intake of five acids was recorded in two-bottle preference tests, one bottle containing acid and the other tap water, before and after miraculin treatment. All the acids tasted more pleasant after miraculin.3. The electrical activity of the chorda tympani nerve to stimulation of the tongue with a variety of sweeteners, acids, sodium chloride and quinine hydrochloride was recorded in anaesthetized animals.4. Pre-treatment of the tongue with 0.3-5 mg miraculin doubled the summated nerve response to the acids and diminished the response to sucrose by about 10%. The enhancement lasted for at least an hour and the diminution up to 20 min.5. After miraculin treatment the Spearman's rank correlation coefficient between the order of increased intake of acids and the order of enhancement of the summated nerve response was 0.99.6. A solution of 0.1 mg miraculin per ml. elicited a weak nerve response. No preference over water for this concentration of miraculin was recorded in the two-bottle tests.7. The activity of twenty-nine single taste fibres, selected for their responsiveness to sweetness or acids or both, was recorded after miraculin treatment. Effects were obtained in nine fibres which were similar but more pronounced than those observed in the summated recordings. Before miraculin, these fibres responded better and to a larger variety of sweeteners (81%) than the other fibres (40%). After miraculin, acids elicited on the average 2.3 times more activity than before, while the response to sweeteners was depressed. In twenty fibres no effect of miraculin was observed. These fibres responded to fewer of the sweeteners and were more stimulated by the non-sweet stimuli than the first group.8. The results suggest that miraculin acts on those structures in the taste cell membrane that are involved in

  18. Associations between Parity, Hair Hormone Profiles during Pregnancy and Lactation, and Infant Development in Rhesus Monkeys (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Amanda M Dettmer

    Full Text Available Studies examining hormones throughout pregnancy and lactation in women have been limited to single, or a few repeated, short-term measures of endocrine activity. Furthermore, potential differences in chronic hormonal changes across pregnancy/lactation between first-time and experienced mothers are not well understood, especially as they relate to infant development. Hormone concentrations in hair provide long-term assessments of hormone production, and studying these measures in non-human primates allows for repeated sampling under controlled conditions that are difficult to achieve in humans. We studied hormonal profiles in the hair of 26 female rhesus monkeys (Macaca mulatta, n=12 primiparous, to determine the influences of parity on chronic levels of cortisol (hair cortisol concentration, HCC and progesterone (hair progesterone concentration, HPC during early- to mid-pregnancy (PREG1, in late pregnancy/early lactation (PREG2/LACT1, and in peak lactation (LACT2. We also assessed infants' neurobehavioral development across the first month of life. After controlling for age and stage of pregnancy at the first hair sampling period, we found that HCCs overall peaked in PREG2/LACT1 (p=0.02, but only in primiparous monkeys (p<0.001. HPCs declined across pregnancy and lactation for all monkeys (p<0.01, and primiparous monkeys had higher HPCs overall than multiparous monkeys (p=0.02. Infants of primiparous mothers had lower sensorimotor reflex scores (p=0.02 and tended to be more irritable (p=0.05 and less consolable (p=0.08 in the first month of life. Moreover, across all subjects, HCCs in PREG2/LACT1 were positively correlated with irritability (r(s=0.43, p=0.03 and negatively correlated with sensorimotor scores (r(s=-0.41, p=0.04. Together, the present results indicate that primiparity influences both chronic maternal hormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in

  19. 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.

  20. Testing for localized stimulus enhancement and object movement reenactment in pig-tailed macaques (Macaca nemestrina) and young children (Homo sapiens).

    Science.gov (United States)

    Rigamonti, Marco M; Custance, Deborah M; Previde, Emanuela Prato; Spiezio, Caterina

    2005-08-01

    Four puzzle boxes were used to investigate localized stimulus enhancement and object movement reenactment (OMR) in 13 pig-tailed macaques (Macaca nemestrina) and 30 human infants (Homo sapiens). Participants received contrasting demonstrations on each box. A circular lid was gripped by its rim or handle and swiveled to the left or right. A flap door was pushed or flipped. A sliding lid was pushed to the left or right. A pin bolt was demonstrated being pushed down, or the participants were left to solve the puzzle for themselves. Despite the fact that the monkeys watched the demonstrations about 60% of the time, only a weak OMR effect was found on the sliding lid. In contrast, the children watched significantly more, and there was clear evidence of socially mediated learning on all of the boxes.

  1. Automated recording of individual performance and hand preference during joystick-task acquisition in group-living bonnet macaques (Macaca radiata).

    Science.gov (United States)

    Andrews, M W; Rosenblum, L A

    1994-12-01

    A microchip that provided a unique identification number was injected into each forearm of all 8 members of a bonnet macaque (Macaca radiata) social group. The group was then given computer-controlled joystick tasks of increasing difficulty. The identification number of the arm used on each trial was input into the computer and used to determine individual performance and hand preference in more than 23,000 trials. Three subjects reversed hand preference as task difficulty was increased over time. All subjects exhibited nearly exclusive use of a single hand on the most difficult task; 6 used the right hand, and 2 used the left. Daily patterns of joystick activity for the group members differed somewhat from that of our individually housed monkeys.

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

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    Jiang Xue-Long

    2009-06-01

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

  3. Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers, mineral density, strength and histomorphometry in ovariectomized cynomolgus monkeys.

    Science.gov (United States)

    Yamada, Hiroyuki; Ochi, Yasuo; Mori, Hiroshi; Nishikawa, Satoshi; Hashimoto, Yasuaki; Nakanishi, Yasutomo; Tanaka, Makoto; Bruce, Mark; Deacon, Steve; Kawabata, Kazuhito

    2016-05-01

    We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30mg/kg/day, p.o.), alendronate (0.05mg/kg/2weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N=20) for 16months. A concurrent Sham group (N=20) was also treated with vehicle for 16months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones.

  4. The Role of VP1 Amino Acid Residue 145 of Enterovirus 71 in Viral Fitness and Pathogenesis in a Cynomolgus Monkey Model.

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    Chikako Kataoka

    2015-07-01

    Full Text Available Enterovirus 71 (EV71, a major causative agent of hand, foot, and mouth disease, occasionally causes severe neurological symptoms. We identified P-selectin glycoprotein ligand-1 (PSGL-1 as an EV71 receptor and found that an amino acid residue 145 in the capsid protein VP1 (VP1-145 defined PSGL-1-binding (PB and PSGL-1-nonbinding (non-PB phenotypes of EV71. However, the role of PSGL-1-dependent EV71 replication in neuropathogenesis remains poorly understood. In this study, we investigated viral replication, genetic stability, and the pathogenicity of PB and non-PB strains of EV71 in a cynomolgus monkey model. Monkeys were intravenously inoculated with cDNA-derived PB and non-PB strains of EV71, EV71-02363-EG and EV71-02363-KE strains, respectively, with two amino acid differences at VP1-98 and VP1-145. Mild neurological symptoms, transient lymphocytopenia, and inflammatory cytokine responses, were found predominantly in the 02363-KE-inoculated monkeys. During the early stage of infection, viruses were frequently detected in clinical samples from 02363-KE-inoculated monkeys but rarely in samples from 02363-EG-inoculated monkeys. Histopathological analysis of central nervous system (CNS tissues at 10 days postinfection revealed that 02363-KE induced neuropathogenesis more efficiently than that induced by 02363-EG. After inoculation with 02363-EG, almost all EV71 variants detected in clinical samples, CNS, and non-CNS tissues, possessed a G to E amino acid substitution at VP1-145, suggesting a strong in vivo selection of VP1-145E variants and CNS spread presumably in a PSGL-1-independent manner. EV71 variants with VP1-145G were identified only in peripheral blood mononuclear cells in two out of four 02363-EG-inoculated monkeys. Thus, VP1-145E variants are mainly responsible for the development of viremia and neuropathogenesis in a non-human primate model, further suggesting the in vivo involvement of amino acid polymorphism at VP1-145 in cell

  5. 食蟹猴脐带间充质干细胞的分离与鉴定%Isolation and identification of cynomolgus monkey umbilical cord mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    庞荣清; 何洁; 李瑞生; 赵晶; 朱慧; 朱向情; 阮光萍; 潘兴华

    2015-01-01

    目的:建立食蟹猴脐带间充质干细胞的分离培养方法。方法新鲜食蟹猴脐带剪碎为糊状,用含10%胎牛血清的DMEM/F12培养液培养,观察细胞形态特征,流式细胞技术分析细胞抗原标志的表达,并检测其体外多向分化潜能。结果运用组织贴块法可以从新鲜脐带中分离到贴壁生长、阳性表达CD29、CD44、CD90的成纤维细胞样细胞。这些细胞在体外诱导培养后可分别检测到脂滴、骨和软骨细胞。结论运用组织贴块培养法可用含10%胎牛血清的DMEM/F12培养液从食蟹猴脐带中分离到间充质干细胞。%Objective To establish a method for isolation of cynomolgus monkey umbilical cord mesenchymal stem cells.Methods Fresh cynomolgus monkey umbilical cord was directly minced into pasty fine pieces, and the pieces were cultured in tissue flask with DMEM/F12 medium supplemented with 10% fetal bovine serum.The morphological characteristics of the resulting cells were examined, and their expression of mesenchymal cell surface markers were analyzed by flow cytometry.The multidifferentiation potential was examined in vitro, too.Results The fibroblast-like cells were successfully isolated from the fresh umbilical cord by an adherent culture procedure.These adherent cells expressed mesenchymal markers including CD29, CD44, and CD90, and also could be induced to differentiate into adipocytes, osteoblasts and chondrocytes.Conclusion Mesenchymal stem cells can be isolated from fresh cynomolgus monkey umbilical cord by using an adherent culture procedure.

  6. Alterações nucleares das cellulas do figado nas infecções de Macacus Rhesus e M. Cynomolgus pelo virus da febre amarella

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    C. Magarinos Torres

    1928-01-01

    Full Text Available No figado de um Macacus rhesus inoculado por BEAUREPAIRE ARAGÃO com sangue deum caso benigno de febre amarella e no qual elle descreveu symptomas e lesões typicas semelhantes ás obidas por STOKES, BAUER e HUDSON pela inoculação com o virus africano no mesmo animal, encontrámos alterações nucleares da mesma natureza das assignaladas, no herpes zoster, herpes symptomatico, varicella e virus III do coelho e descriptas ora sob o nome de "inclusões acidophilas intranucleares" (LIPSCHÜTZ, GOODPASTURE, ora sob o de "degeneração oxychromatica" (LAUDA e LUGER. Alterações nucleares semelhantes da cellula hepatica encontrámos, posteriormente em 13 M. rhesus e 2 M. cynomolgus inoculados com e virus brasileiro da febre amarella o qual fôra isolado independentemente por BEAUREPAIRE ARAGÂO e depois por A. MARQUES DA CUNHA e J. MUNIZ de dois casos benignos de febre amarella, tendo sido um dos macacos injectado directamente com o sangue do doente; dois macacos foram inoculados com Aedes aegypti infectados em homem e em macaco; os animais foram anímaes empregados em passagens em serie do virus pelo macaco, e talvez esse facto explique até certo ponto, as notaveis differenças por vezes encontradas nas alterações histopathologicas do figado, visto como, em condições naturaes, o virus nunca passa directamente de homem para homem. A intensidade com que se apresenta a degeneração oxychromatica de modo algum está na dependencia das alterações do conteúdo gorduroso, necrose e necrobiose encontradas; em um caso, ella era a unica alteração presente no figado, sendo então particularmente intensa. As inclusões acidophilas intranucleares (degeneração oxychromatica não foram encontradas em diversos M. rhesus não inoculados e mortos por causas obscuras; no entanto, em taes figados eram presentes infiltração e degeneração gordurosas associadas a alterações de necrose e necrobiose. Alguns estadios (figuras intranucleares "em borboleta

  7. MR experiments study on the brain of cynomolgus of diabetic models%食蟹猴糖尿病模型脑部MR检查的实验研究

    Institute of Scientific and Technical Information of China (English)

    宋英儒; 叶伟; 黄仲奎; 滕夏虹; 张愚; 邹春林

    2009-01-01

    Objective To investigate the value of MRI and~1H-MRS in diagnosis of early stage of diabetic encephalopathy by detecting regional metabolite in cynomolgus diabetes models. Methods Five pathogen-free male adolescent cynomolgus were made type 1 diabetes mellitus models (T1DM) by intravenous injection of streptozotocin (STZ) (100 mg/kg), and the reliability and stability of the modes were assessed with long term follow-up of blood glucose and intravenous glucose tolerance tests. MRI and ~1H-MRS were performed to evaluate the volume, signal intensity and metabolic ratios of NAA/Cr, mI/Cr and Cho/Cr at hippocampus