Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

2016-01-01

Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

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

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

PubMed

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.

Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca fascicularis

PubMed Central

Dobrikova, Elena Y.; Goetz, Christian; Walters, Robert W.; Lawson, Sarah K.; Peggins, James O.; Muszynski, Karen; Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L.; Vela, Eric M.; Estep, James E.

2012-01-01

A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied. PMID:22171271

Selection and Investigation of a Primate Model of Spontaneous Degenerative Knee Osteoarthritis, the Cynomolgus Monkey (Macaca Fascicularis).

PubMed

Liu, Gang; Zhang, Lei; Zhou, Xin; Zhang, Bao L; Guo, Guang X; Xu, Ping; Wang, Guo Y; Fu, Shi J

2018-07-01

BACKGROUND The aim of this study was to identify a primate model of degenerative knee osteoarthritis (KOA) that may be more relevant for research studies on degenerative KOA in humans. MATERIAL AND METHODS Sixteen specific-pathogen-free (SPF) male cynomolgus monkeys (Macaca fascicularis) were divided into group A (n=8), an old group (22.0-25.3 years of age), and group B (n=8), a young group (3.0-5.2 years of age). For each primate, the behavior was observed, knee circumference was measured, knee joint X-rays were performed, and peripheral blood white blood cell (WBC) counts were measured, and the Kellgren and Lawrence (K-L) system was used for the classification of osteoarthritis. An enzyme-linked immunoassay (ELISA) was performed on knee joint fluid to measure levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)13. Changes in articular cartilage were evaluated using the Brittberg score and the Mankin histopathology grading score, respectively. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were used to measure the expression of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and the findings in the two groups of primates were compared. RESULTS Seven old aged primates in group A were compared with group B, and showed significant differences in WBC count, synovial fluid IL-1β, TGF-β1, and MMP13 levels, expression levels of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and in the Brittberg and Mankin scores (all, P<0.05). CONCLUSIONS Cynomolgus monkeys (Macaca fascicularis) might be a model for age-related degenerative KOA.

Morphological characteristics and genetic diversity of Burmese long-tailed Macaques (Macaca fascicularis aurea).

PubMed

Bunlungsup, Srichan; Imai, Hiroo; Hamada, Yuzuru; Gumert, Michael D; San, Aye Mi; Malaivijitnond, Suchinda

2015-12-15

Macaca fascicularis aurea (Mfa) is the only macaque which has been recorded to use stone tools to access encased foods. They live in close contact with M. fascicularis fascicularis (Mff) in southwestern Thailand and the hybrids were reported [Fooden, 1995]. Although Mff and Mfa can be seen in the same habitat types, tool-use behavior has never been reported in Mff. Thus, comparing the morphological characteristics and genetics between Mfa and Mff should help elucidate not only the morphological differences and genetic divergence between these subspecies but also potentially the relationship between genetics and their tool use behavior. We surveyed Mfa and Mff in Myanmar and Thailand, ranging from 16° 58' to 7° 12' N. Fecal or blood samples were collected from eight, five, and four populations of Mfa, Mff, and Mff × Mfa morphological hybrids along with three individuals of captive Chinese M. mulatta (Mm), respectively, for mtDNA and Y-chromosome (TSPY and SRY genes) DNA sequence analyses. In addition, eight populations were captured and measured for 38 somatometric dimensions. Comparison of the somatic measurements revealed that Mfa had a statistically significantly shorter tail than Mff (P < 0.05). Based on the mtDNA sequences, Mfa was separated from the Mm/Mff clade. Within the Mfa clade, the mainland Myanmar population was separate from the Mergui Archipelago and Thailand Andaman seacoast populations. All the morphological hybrids had the Mff mtDNA haplotype. Based on the Y-chromosome sequences, the three major clades of Mm/Indochinese Mff, Sundaic Mff, and Mfa were constructed. The hybrid populations grouped either with the Mm/Indochinese Mff or with the Mfa. Regarding the genetic analysis, one subspecies hybrid population in Thailand (KRI) elicited tool use behavior, thus the potential role of genetics in tool use behavior is raised in addition to the environmental force, morphological suitability, and cognitive capability. Am. J. Primatol. © 2015

Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human.

PubMed

Magness, Charles L; Fellin, P Campion; Thomas, Matthew J; Korth, Marcus J; Agy, Michael B; Proll, Sean C; Fitzgibbon, Matthew; Scherer, Christina A; Miner, Douglas G; Katze, Michael G; Iadonato, Shawn P

2005-01-01

We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported.

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

PubMed

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

2016-01-01

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

A quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections.

PubMed

Li, Hao; Lei, Xiaoguang; Huang, Baihui; Rizak, Joshua D; Yang, Lichuan; Yang, Shangchuan; Wu, Jing; Lü, Longbao; Wang, Jianhong; Yan, Ting; Li, Hongwei; Wang, Zhengbo; Hu, Yingzhou; Le, Weidong; Deng, Xingli; Li, Jiali; Xu, Lin; Zhang, Baorong; Hu, Xintian

2015-08-15

Non-human primate Parkinson's disease (PD) models are essential for PD research. The most extensively used PD monkey models are induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the modeling processes of developing PD monkeys cannot be quantitatively controlled with MPTP. Therefore, a new approach to quantitatively develop chronic PD monkey models will help to advance the goals of "reduction, replacement and refinement" in animal experiments. A novel chronic PD monkey models was reported using the intracerebroventricular administration of 1-methyl-4-phenylpyridinium (MPP(+)) in Cynomolgus monkeys (Macaca fascicularis). This approach successfully produced stable and consistent PD monkeys with typical motor symptoms and pathological changes. More importantly, a sigmoidal relationship (Y=8.15801e(-0.245/x); R=0.73) was discovered between PD score (Y) and cumulative dose of MPP(+) (X). This relationship was then used to develop two additional PD monkeys under a specific time schedule (4 weeks), with planned PD scores (7) by controlling the dose and frequency of the MPP(+) administration as an independent validation of the formula. We developed Parkinsonian monkeys within controlled time frames by regulating the accumulated dose of MPP(+) intracerebroventricular administered, while limiting side effects often witnessed in models developed with the peripheral administration of MPTP, makes this model highly suitable for treatment development. This novel approach provides an edge in evaluating the mechanisms of PD pathology associated with environmental toxins and novel treatment approaches as the formula developed provides a "map" to control and predict the modeling processes. Copyright © 2015 Elsevier B.V. All rights reserved.

No costly prosociality among related long-tailed macaques (Macaca fascicularis).

PubMed

Sterck, Elisabeth H M; Olesen, Caroline U; Massen, Jorg J M

2015-08-01

Altruism, benefiting another at a cost to the donor, may be achieved through prosocial behavior. Studies of nonhuman animals typically investigate prosocial behavior with paradigms in which the donor can choose to give a recipient a food item, and the choice does not affect the donor's reward (which is either present or absent). In such tasks, long-tailed macaques (Macaca fascicularis) show prosocial behavior, especially toward kin. Here, we tested captive long-tailed macaques with related recipients in an alternative task, in which the donor had to give up a preferred reward to benefit the recipient; that is, they had to choose a lower valued reward for themselves to provide food to their kin. Overall, the macaques did not provide their kin with food. The task forced the donor to balance its prosocial behavior with its selfish choice for a higher value reward, a balance that turned out to favor selfish motives. Consequently, our study shows that a prosocial tendency is not sufficient to elicit costly prosocial behavior in long-tailed macaques. Subsequently, we feel that tasks in which the donor must choose a lower value reward to benefit another individual may allow the titration of the strength of prosocial behavior, and thus provides interesting possibilities for future comparative studies. (c) 2015 APA, all rights reserved).

Comparison of Saliva Collection Methods for the Determination of Salivary Cortisol Levels in Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), and African Green Monkeys (Chlorocebus aethiops)

PubMed Central

Rapp-Santos, Kamala J; Altamura, Louis A; Norris, Sarah L; Lugo-Roman, Luis A; Rico, Pedro J; Hofer, Christian C

2017-01-01

The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis) and African green monkeys (Chlorocebus aethiops) at 2 collection time points. Serum and salivary cortisol levels were determined using a competitive quantitative ELISA. In addition, both saliva collection methods were evaluated for volume collected and ease of use. Compared with passive drool, the experimental collection device was more reliable in collecting sufficient volumes of saliva, and the resulting salivary cortisol values demonstrated stronger correlation with serum cortisol concentration in all species and collection days except cynomolgus macaques on day 1. This saliva collection device allows quick and reliable sample collection for the determination of salivary cortisol levels. In addition, the results might provide a useful tool for evaluating hypothalamic-pituitary-adrenal axis activity or the physiologic stress reaction in NHP as well as a biomarker of psychologic stress states in a variety of situations. PMID:28315649

Large-scale transcriptome sequencing and gene analyses in the crab-eating macaque (Macaca fascicularis) for biomedical research

PubMed Central

2012-01-01

Background As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use. Results Here, we sequenced the transcriptome of 16 tissues originated from two individuals of crab-eating macaque (male and female), and identified genes to resolve the main obstacles for understanding the biological response of the crab-eating macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS FLX sequencing method. Approximately 86% of human genes were represented among the genes sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed. Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally, investigation of TE exonization events and evolutionary analysis were conducted, revealing interesting phenomena of human-specific amplified trends in TE exonization events. Conclusions This report represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and could contribute to its utility for biomedical research and basic biology. PMID:22554259

Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

2011-01-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

PubMed

Fong, Derek L; Murnane, Robert D; Hotchkiss, Charlotte E; Green, Damian J; Hukkanen, Renee R

2011-02-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.

Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.

PubMed

Herrera, Loren P; Casas, Carlos E; Bates, Margaret L; Guest, James D

2005-08-08

Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within the olfactory pathway. OEGs are thought to exclude OAs from contact with all other cells between the olfactory epithelium and the glomerulus of the olfactory bulb. These properties have lead to testing to determine whether OEGs support axonal growth following transplantation. The cellular interactions of transplanted OEGs will probably resemble those that occur within the normal pathway where interactions between OEGs and fibroblasts are prominent. No previous primate studies have focused on these interactions, knowledge of which is important if clinical application is envisioned. We describe the detailed intercellular interactions of OAs with supporting cells throughout the olfactory epithelium, the lamina propria, the fila olfactoria, and the olfactory nerve layer by using transmission electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment and variations of the endo- and perineurium formed by olfactory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. Perineurial cells contained intermediate filaments and were distinct from other fibroblasts and meningeal cells. OAs had direct contacts with astrocytes near the glia limitans. The properties of OEGs differed depending on whether astrocytic or fibroblastic processes were present. This indicates the importance of the cellular milieu in the structure and function of OEGs in primates.

A crypto-lymphatic unit at the uvula of the monkey Macaca fascicularis. A light- and electron-microscopic study.

PubMed

Nair, P N

1983-01-01

A crypto-lymphatic unit was observed at the left lateral aspect of the uvula of a mature female monkey, Macaca fascicularis. A light- and transmission electron-microscopic investigation revealed that the lumen of the crypt was filled with bacteria, desquamated epithelial cells, lymphocytes and neutrophils. The non-keratinized stratified squamous epithelium of the crypt was fragmented and showed heavy mononuclear cell infiltration and surface discontinuities, exposing lymphoid cells to foreign material. The lymphatic parenchyma consisted of organized lymphatic tissue including germinal centres. The resident cell population included lymphocytes of varying size, blastforming B- and T-lymphocytes and two types of reticular cells resembling the fibroblastic reticulum cell and the follicular dendritic cell, respectively. Occasionally granulocytes were encountered. At its base and laterally the crypto-lymphatic unit was ensheathed by a thin connective tissue capsule. Three other monkeys of the same species failed to reveal similar structures at the same site.

Pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (Macaca fascicularis).

PubMed

Kuiken, Thijs; Buijs, Pascal; van Run, Peter; van Amerongen, Geert; Koopmans, Marion; van den Hoogen, Bernadette

2017-11-21

Although avian paramyxovirus type 1 is known to cause mild transient conjunctivitis in human beings, there are two recent reports of fatal respiratory disease in immunocompromised human patients infected with the pigeon lineage of the virus (PPMV-1). In order to evaluate the potential of PPMV-1 to cause respiratory tract disease, we inoculated a PPMV-1 isolate (hPPMV-1/Netherlands/579/2003) from an immunocompromised human patient into three healthy cynomolgus macaques (Macaca fascicularis) and examined them by clinical, virological, and pathological assays. In all three macaques, PPMV-1 replication was restricted to the respiratory tract and caused pulmonary consolidation affecting up to 30% of the lung surface. Both alveolar and bronchiolar epithelial cells expressed viral antigen, which co-localized with areas of diffuse alveolar damage. The results of this study demonstrate that PPMV-1 is a primary respiratory pathogen in cynomolgus macaques, and support the conclusion that PPMV-1 may cause fatal respiratory disease in immunocompromised human patients.

Microspectrophotometric demonstration of four classes of photoreceptor in an old world primate, Macaca fascicularis.

PubMed Central

Bowmaker, J K; Dartnall, H J; Mollon, J D

1980-01-01

1. Microspectrophotometric measurements reveal four classes of photoreceptor in the retina of the cynomolgus monkey, Macaca fascicularis, which is known to possess colour vision similar to that of a normal human trichromat. 2. Although the eyes were removed in bright illumination, the densities of pigment were comparable to those we have measured in dark-adapted rhesus retinae. 3. The mean wave-lengths of peak sensitivity (lambda max) for the four classes of photoreceptor were 415, 500, 535 and 567 nm. 4. The band widths of the absorbance spectra decreased linearly as the wave-number of peak sensitivity decreased. 5. If, by assuming a reasonable value for the axial density of the rod outer segment and correcting for lens absorption, a spectral sensitivity for human vision is reconstructed from the P500 pigment, it is found to be systematically broader than the CIE scotopic sensitivity function. 6. Given explicit assumptions, it is possible from the P535 and P567 pigments to reconstruct human psychophysical sensitivities that resemble the pi 4 and pi 5 mechanisms of W. S. Stiles. 7. Although the P415 pigment has a lambda max much shorter than that of the psychophysically measured blue mechanisms, the two spectral-sensitivity functions are brought into proximity when the microspectrophotometric data are corrected for absorption by the optic media. Images Fig. 1 PMID:6767023

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

PubMed

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.

Compete to Play: Trade-Off with Social Contact in Long-Tailed Macaques (Macaca fascicularis)

PubMed Central

Ballesta, Sébastien; Reymond, Gilles; Pozzobon, Mathieu; Duhamel, Jean-René

2014-01-01

Many animal species engage in various forms of solitary object play, but this activity seems to be of particular importance in primates. If playing objects constitute a valuable resource, and access to such objects is limited, a competitive context may arise. We inserted a unique toy within a mini-colony of long-tailed macaque (Macaca fascicularis) and compared their behaviors to sessions without playing object. An automatic color-based 3D video device was used to track the positions of each animal and the toy, and this data was categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). As expected, the delay to first access to the object reflected the hierarchy of the colony, indicating that a competition took place to own this unique resource of entertainment. In addition, we found that the amount of object play was not correlated with social or foraging behavior, suggesting independent motivational mechanisms. Conversely, object playing time was negatively correlated with idling time, thus indicating its relation to pastime activities. Interestingly, the amount of social contacts in the group was significantly reduced by the heightened competitive context, suggesting that competitors are more likely to be perceived as potential threat requiring caution, as shown in humans. Experimental manipulation of competitive contexts in primates reveals common mental processes involved in social judgment, and shows that access to valuable resources can be a sufficient cause for variations in group cohesion. PMID:25551755

Thoracic Radiography as a Refinement Methodology for the Study of H1N1 Influenza in Cynomologus Macaques (Macaca fascicularis)

PubMed Central

Brining, Douglas L; Mattoon, John S; Kercher, Lisa; LaCasse, Rachael A; Safronetz, David; Feldmann, Heinz; Parnell, Michael J

2010-01-01

Recent advances in the technology associated with digital radiography have created new opportunities for biomedical research applications. Here we evaluated the use of thoracic radiography as a noninvasive refinement methodology for the cynomologus macaque (Macaca fascicularis) model of H1N1 infection. Thoracic radiographic evaluations of macaques infected with any of 3 strains of emerging H1N1 swine-associated influenza virus isolated during the recent pandemic were compared with those of macaques infected with the currently circulating Kawasaki strain of H1N1 influenza. Ventrodorsal, right, and left lateral thoracic radiographs were obtained at days 0, 1, 6, 8, 11, and 14 after infection. A board-certified veterinary radiologist who was blinded to the study design evaluated the images. Numeric scores of extent and severity of lung involvement assigned to each radiograph were compared and demonstrated a significant and substantial difference among groups. The radiographic evaluation allowed for noninvasive assessment of lung involvement, disease onset, progression, and resolution of radiographic changes associated with H1N1 influenza infection. PMID:21262125

Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

PubMed Central

Whitehouse, Chris A.; Chase, Kitty; Embers, Monica E.; Kulesh, David A.; Ladner, Jason T.; Palacios, Gustavo F.; Minogue, Timothy D.

2016-01-01

Background Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. Methods We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. Results All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. Conclusions We developed several accurate, sensitive, and species-specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID:26365904

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

PubMed Central

2011-01-01

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 < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. 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. PMID:21999700

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study

PubMed Central

Fitton, L C; Shi, J F; Fagan, M J; O’Higgins, P

2012-01-01

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the

Investigating biogeographic boundaries of the Sunda shelf: A phylogenetic analysis of two island populations of Macaca fascicularis.

PubMed

Klegarth, A R; Sanders, S A; Gloss, A D; Lane-deGraaf, K E; Jones-Engel, L; Fuentes, A; Hollocher, H

2017-08-01

Cyclical submergence and re-emergence of the Sunda Shelf throughout the Pleistocene served as a dynamic biogeographic landscape, across which long-tailed macaques (Macaca fascicularis) have migrated and evolved. Here, we tested the integrity of the previously reported continental-insular haplotype divide reported among Y and mitochondrial DNA lineages across multiple studies. The continental-insular haplotype divide was tested by heavily sampling wild macaques from two important biogeographic regions within Sundaland: (1) Singapore, the southernmost tip of continental Asia and (2) Bali, Indonesia, the southeastern edge of the Indonesian archipelago, immediately west of Wallace's line. Y DNA was haplotyped for samples from Bali, deep within the Indonesian archipelago. Mitochondrial D-loop from both islands was analyzed against existing data using Maximum Likelihood and Bayesian approaches. We uncovered both "continental" and "insular" Y DNA haplotypes in Bali. Between Singapore and Bali we found 52 unique mitochondrial haplotypes, none of which had been previously described. Phylogenetic analyses confirmed a major haplogroup division within Singapore and identified five new Singapore subclades and two primary subclades in Bali. While we confirmed the continental-insular divide among mtDNA haplotypes, maintenance of both Y DNA haplotypes on Bali, deep within the Indonesian archipelago calls into question the mechanism by which Y DNA diversity has been maintained. It also suggests the continental-insular designation is less appropriate for Y DNA, leading us to propose geographically neutral Y haplotype designations. © 2017 Wiley Periodicals, Inc.

Finding the factors of reduced genetic diversity on X chromosomes of Macaca fascicularis: male-driven evolution, demography, and natural selection.

PubMed

Osada, Naoki; Nakagome, Shigeki; Mano, Shuhei; Kameoka, Yosuke; Takahashi, Ichiro; Terao, Keiji

2013-11-01

The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.34 and 0.20 in the Indonesian-Malaysian and Philippine populations, respectively, considerably lower than the null expectation of 0.75. A Philippine population supposed to derive from an ancestral population by founding events showed a significantly lower ratio than the parental population, suggesting a demographic effect for the reduction. Taking sex-specific mutation rate bias and demographic effect into account, expected X/A diversity ratios generated by computer simulations roughly agreed with the observed data in the intergenic regions. In contrast, silent sites in genic regions on X chromosomes showed strong reduction in genetic diversity and the observed X/A diversity ratio in the genic regions cannot be explained by mutation rate bias and demography, indicating that natural selection also reduces the level of polymorphism near genes. Whole-genome analysis of a female cynomolgus monkey also supported the notion of stronger reduction of genetic diversity near genes on the X chromosome.

Finding the Factors of Reduced Genetic Diversity on X Chromosomes of Macaca fascicularis: Male-Driven Evolution, Demography, and Natural Selection

PubMed Central

Osada, Naoki; Nakagome, Shigeki; Mano, Shuhei; Kameoka, Yosuke; Takahashi, Ichiro; Terao, Keiji

2013-01-01

The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.34 and 0.20 in the Indonesian–Malaysian and Philippine populations, respectively, considerably lower than the null expectation of 0.75. A Philippine population supposed to derive from an ancestral population by founding events showed a significantly lower ratio than the parental population, suggesting a demographic effect for the reduction. Taking sex-specific mutation rate bias and demographic effect into account, expected X/A diversity ratios generated by computer simulations roughly agreed with the observed data in the intergenic regions. In contrast, silent sites in genic regions on X chromosomes showed strong reduction in genetic diversity and the observed X/A diversity ratio in the genic regions cannot be explained by mutation rate bias and demography, indicating that natural selection also reduces the level of polymorphism near genes. Whole-genome analysis of a female cynomolgus monkey also supported the notion of stronger reduction of genetic diversity near genes on the X chromosome. PMID:24026095

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study.

PubMed

Fitton, L C; Shi, J F; Fagan, M J; O'Higgins, P

2012-07-01

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the

The role of anthropic, ecological, and social factors in sleeping site choice by long-tailed macaques (Macaca fascicularis).

PubMed

Brotcorne, Fany; Maslarov, Cindy; Wandia, I Nengah; Fuentes, Agustin; Beudels-Jamar, Roseline C; Huynen, Marie-Claude

2014-12-01

When choosing their sleeping sites, primates make adaptive trade-offs between various biotic and abiotic constraints. In human-modified environments, anthropic factors may play a role. We assessed the influence of ecological (predation), social (intergroup competition), and anthropic (proximity to human settlements) factors in sleeping site choice by long-tailed macaques (Macaca fascicularis) occupying a habitat at the interface of natural forests and human-modified zones in Bali Barat National Park, Indonesia. Over the course of 56 nights, we collected data relating to physical features of sleeping trees, patterns of the use of sleeping sites within the home range, pre-sleep behavior, diurnal ranging patterns and availability of natural and human food. Overall, the macaques used 17 sleeping sites with 37 sleeping trees. When the monkeys slept in forest zones, they selected sleeping trees that had larger trunks but were not significantly taller than surrounding trees. Though the macaques rarely re-used sleeping sites on consecutive nights, they frequently re-used four sites over the study period. The group favored sleeping within the core area of its home range, despite the occurrence of frequent agonistic intergroup encounters there. Macaques preferentially selected sleeping trees located within or near human-modified zones, especially when human food was abundant and natural food was scarce. These results partially support the hypothesis that long-tailed macaques choose their sleeping sites to avoid predation; proximity to human settlements appears to be the primary factor influencing sleeping site choice in this primate species. Our results reflect the strong influence that anthropic factors have on primates, which subsist in increasingly human-dominated landscapes. © 2014 Wiley Periodicals, Inc.

The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.

PubMed Central

Baylor, D A; Nunn, B J; Schnapf, J L

1984-01-01

Visual transduction in rods of the cynomolgus monkey, Macaca fascicularis, was studied by recording membrane current from single outer segments projecting from small pieces of retina. Light flashes evoked transient outward-going photocurrents with saturating amplitudes of up to 34 pA. A flash causing twenty to fifty photoisomerizations gave a response of half the saturating amplitude. The response-stimulus relation was of the form 1-e-x where x is flash strength. The response to a dim flash usually had a time to peak of 150-250 ms and resembled the impulse response of a series of six low-pass filters. From the average spectral sensitivity of ten rods the rhodopsin was estimated to have a peak absorption near 491 nm. The spectral sensitivity of the rods was in good agreement with the average human scotopic visibility curve determined by Crawford (1949), when the human curve was corrected for lens absorption and self-screening of rhodopsin. Fluctuations in the photocurrent evoked by dim lights were consistent with a quantal event about 0.7 pA in peak amplitude. A steady light causing about 100 photoisomerizations s-1 reduced the flash sensitivity to half the dark-adapted value. At higher background levels the rod rapidly saturated. These results support the idea that dim background light desensitizes human scotopic vision by a mechanism central to the rod outer segments while scotopic saturation may occur within the outer segments. Recovery of the photocurrent after bright flashes was marked by quantized step-like events. The events had the properties expected if bleached rhodopsin in the disks occasionally caused an abrupt blockage of the dark current over about one-twentieth of the length of the outer segment. It is suggested that superposition of these events after bleaching may contribute to the threshold elevation measured psychophysically. The current in darkness showed random fluctuations which disappeared in bright light. The continuous component of the noise

The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.

PubMed

Baylor, D A; Nunn, B J; Schnapf, J L

1984-12-01

Visual transduction in rods of the cynomolgus monkey, Macaca fascicularis, was studied by recording membrane current from single outer segments projecting from small pieces of retina. Light flashes evoked transient outward-going photocurrents with saturating amplitudes of up to 34 pA. A flash causing twenty to fifty photoisomerizations gave a response of half the saturating amplitude. The response-stimulus relation was of the form 1-e-x where x is flash strength. The response to a dim flash usually had a time to peak of 150-250 ms and resembled the impulse response of a series of six low-pass filters. From the average spectral sensitivity of ten rods the rhodopsin was estimated to have a peak absorption near 491 nm. The spectral sensitivity of the rods was in good agreement with the average human scotopic visibility curve determined by Crawford (1949), when the human curve was corrected for lens absorption and self-screening of rhodopsin. Fluctuations in the photocurrent evoked by dim lights were consistent with a quantal event about 0.7 pA in peak amplitude. A steady light causing about 100 photoisomerizations s-1 reduced the flash sensitivity to half the dark-adapted value. At higher background levels the rod rapidly saturated. These results support the idea that dim background light desensitizes human scotopic vision by a mechanism central to the rod outer segments while scotopic saturation may occur within the outer segments. Recovery of the photocurrent after bright flashes was marked by quantized step-like events. The events had the properties expected if bleached rhodopsin in the disks occasionally caused an abrupt blockage of the dark current over about one-twentieth of the length of the outer segment. It is suggested that superposition of these events after bleaching may contribute to the threshold elevation measured psychophysically. The current in darkness showed random fluctuations which disappeared in bright light. The continuous component of the noise

Sex differences in the stone tool-use behavior of a wild population of burmese long-tailed macaques (Macaca fascicularis aurea).

PubMed

Gumert, Michael D; Hoong, Low Kuan; Malaivijitnond, Suchinda

2011-12-01

We investigated sex differences in how Burmese long-tailed macaques (Macaca fascicularis aurea) used stone tools to open shelled food items along the shores of two islands in Laemson National Park, Thailand. Over a 2-week period in December 2009, we collected scan and focal samples on macaques when they were visible along the shores and mangroves. We found females used stones more often while feeding and used smaller tools than males. Females also processed sessile oysters more than males, whereas males processed unattached foods more than females. It was unclear which sex was overall more proficient at stone tool use, but males did perform significantly better at opening unattached food items with large pounding stones. Females also struck food items more times during tool-use bouts and at a faster rate, but no significant difference was found in average tool-use bout duration. Males processed foods slightly faster within a tool-use bout, but we were unable to detect a significant difference in the rate of food processing while foraging with tools. In summary females chipped open sessile oysters with an axing technique more than males, while males used larger stones to pound open unattached shelled food more often than females. Despite using pounding more than females, males also regularly utilized the axing technique on sessile oysters. Our results are the first assessment of sex differences in macaque stone tool use, providing a basis for comparison with tool use in other primates, and to nonfunctional forms of stone use in other macaques. © 2011 Wiley Periodicals, Inc.

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

PubMed Central

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

2010-01-01

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 (105 copies/ml), followed by serum viral load of 104 copies/ml at 20 dpi and saliva viral load of 103copies/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 × 104 copies/mg), salivary glands (1.9 × 103 copies/mg), tonsils (4.2 × 101 copies/mg) and lymph nodes (3.4 × 101 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. PMID:20096073

Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India.

PubMed

Velankar, Avadhoot D; Kumara, Honnavalli N; Pal, Arijit; Mishra, Partha Sarathi; Singh, Mewa

2016-01-01

Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species.

Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India

PubMed Central

Velankar, Avadhoot D.; Kumara, Honnavalli N.

2016-01-01

Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species. PMID:26886197

Chitinase mRNA Levels Determined by QPCR in Crab-Eating Monkey (Macaca fascicularis) Tissues: Species-Specific Expression of Acidic Mammalian Chitinase and Chitotriosidase.

PubMed

Uehara, Maiko; Tabata, Eri; Ishii, Kazuhiro; Sawa, Akira; Ohno, Misa; Sakaguchi, Masayoshi; Matoska, Vaclav; Bauer, Peter O; Oyama, Fumitaka

2018-05-09

Mice and humans express two active chitinases: acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Both chitinases are thought to play important roles in specific pathophysiological conditions. The crab-eating monkey ( Macaca fascicularis ) is one of the most frequently used nonhuman primate models in basic and applied biomedical research. Here, we performed gene expression analysis of two chitinases in normal crab-eating monkey tissues by way of quantitative real-time polymerase chain reaction (qPCR) using a single standard DNA molecule. Levels of AMCase and CHIT1 messenger RNAs (mRNAs) were highest in the stomach and the lung, respectively, when compared to other tissues. Comparative gene expression analysis of mouse, monkey, and human using monkey⁻mouse⁻human hybrid standard DNA showed that the AMCase mRNA levels were exceptionally high in mouse and monkey stomachs while very low in the human stomach. As for the CHIT1 mRNA, we detected higher levels in the monkey lung when compared with those of mouse and human. The differences of mRNA expression between the species in the stomach tissues were basically reflecting the levels of the chitinolytic activities. These results indicate that gene expression of AMCase and CHIT1 differs between mammalian species and requiring special attention in handling data in chitinase-related studies in particular organisms.

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

PubMed

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.

Colour cues for leaf food selection by long-tailed macaques (Macaca fascicularis) with a new suggestion for the evolution of trichromatic colour vision.

PubMed

Lucas, P W; Darvell, B W; Lee, P K; Yuen, T D; Choong, M F

1998-01-01

Leaf colour, size and toughness were investigated in five plant species important in the diet of Macaca fascicularis in Singapore. Leaf colour and size were examined as potential visual cues for food selection, whereas toughness mirrored fibre content, the inverse of food quality. As leaves matured, they changed colour and toughened. Leaf lightness and yellowness were strongly negatively correlated with toughness, but variation in both the red-green axis of the CIE Lab colour space and leaf size were not. Leaves selected as food by the macaques were distinguished by being very light, yellow to slightly green. Some leaves were dappled with red. The literature suggests that these leaves are relatively rich in protein without being tough and therefore would be sought after by primates. We argue that leaf colour is an important indicator of the nutritive value of leaves. Trichromatic vision is an important advantage in finding those palatable leaves that are dappled red. These would appear dark to dichromatic primates and be deceptive by making leaves look older (lower in quality) than they actually are. This would decrease the perceived window of feeding opportunity for such primates who would be at a disadvantage in trying to find these leaves. It is possible that trichromatic vision in catarrhine primates may have originally evolved for the detection of red coloration in the leaves of shade-tolerant tropical plants, enabling the better exploitation of a food resource.

A simple orchidometric method for the preliminary assessment of maturity status in male cynomolgus monkeys (Macaca fascicularis) used for nonclinical safety studies.

PubMed

Ku, Warren W; Pagliusi, Frank; Foley, George; Roesler, Alfred; Zimmerman, Thomas

2010-01-01

The identification and use of mature male non-human primates in nonclinical toxicology studies could be important for evaluating candidate drugs for which the profile of toxicity may differ depending on sexual maturity. This investigation sought to establish operational criteria to complement the current standard of histological evaluation for defining sexual maturity in male cynomolgus monkeys (Macaca fascicularis) used for toxicology studies, and to identify a practical non-invasive measure to select mature males for study. Retrospectively, the relationships between body weight, testicular weight and testis histology were established in control males (n=126) used in previous toxicology studies. Prospectively, testicular volumes were measured in-life by orchidometry using comparative scrotal palpation (n=23 males used for study), then compared to testicular weights measured at necropsy. Consistent with previous literature, a weak relationship was observed between body weight and testicular weight. There was, however, a very good relationship between testicular weight and histological maturation level, which was based upon microscopic examination of testes, epididymides and prostates. Orchidometric measurement of testicular volume was found to be a reasonable predictor of testicular weight and served to rapidly select sexually mature males for study, and a total testicular volume (left and right combined) of >20 ml correlated with the histological appearance of maturity. Based upon this preliminary exploratory study, the initial simple measurement of testicular volume by orchidometry may provide a non-invasive alternative approach for assessing the sexual maturity of male cynomolgus monkeys in research colonies or during toxicology studies that will require more thorough validation. Copyright 2009 Elsevier Inc. All rights reserved.

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

PubMed

Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

2015-10-01

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Stress in cynomolgus monkeys (Macaca fascicularis) subjected to long-distance transport and simulated transport housing conditions.

PubMed

Fernström, A L; Sutian, W; Royo, F; Westlund, K; Nilsson, T; Carlsson, H-E; Paramastri, Y; Pamungkas, J; Sajuthi, D; Schapiro, S J; Hau, J

2008-11-01

The stress associated with transportation of non-human primates used in scientific research is an important but almost unexplored part of laboratory animal husbandry. The procedures and routines concerning transport are not only important for the animals' physical health but also for their mental health as well. The transport stress in cynomolgus monkeys (Macaca fascicularis) was studied in two experiments. In Experiment 1, 25 adult female cynomolgus monkeys were divided into five groups of five animals each that received different diets during the transport phase of the experiment. All animals were transported in conventional single animal transport cages with no visual or tactile contact with conspecifics. The animals were transported by lorry for 24 h at ambient temperatures ranging between 20 degrees C and 35 degrees C. Urine produced before, during and after transport was collected and analysed for cortisol by enzyme-linked immunosorbent assay (ELISA). All monkeys exhibited a significant increase in cortisol excretion per time unit during the transport and on the first day following transport.Although anecdotal reports concerning diet during transport, including the provision of fruits and/or a tranquiliser, was thought likely to influence stress responses, these were not corrobated by the present study. In Experiment 2, behavioural data were collected from 18 cynomolgus macaques before and after transfer from group cages to either single or pair housing, and also before and after a simulated transport, in which the animals were housed in transport cages. The single housed monkeys were confined to single transport cages and the pair housed monkeys were kept in their pairs in double size cages. Both pair housed and singly housed monkeys showed clear behavioural signs of stress soon after their transfer out of their group cages.However, stress-associated behaviours were more prevalent in singly housed animals than in pair housed animals, and these behaviours

Use of photogrammetry as a means to assess hybrids of rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques.

PubMed

Jadejaroen, Janya; Hamada, Yuzuru; Kawamoto, Yoshi; Malaivijitnond, Suchinda

2015-01-01

Rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques are the most commonly used non-human primate models for biomedical research, but it is difficult to identify these two species in the hybrid zone (15-20°N). In this work, we used morphological values obtained via photogrammetry to assess hybrids of rhesus and long-tailed macaques at Khao Khieow Open Zoo (KKZ; 13°21'N, 101°06'E), eastern Thailand. Long-tailed and rhesus macaques have species-specific tail lengths and contrasts of their yellowish pelages. The accuracy and precision of the relative tail length (%RTL) and the contrast of the yellow hue (Cb*) of the pelage, as obtained from photographs, were compared with the corresponding direct measurements (morphometrics). The photogrammetric and morphometric measurements of %RTL and Cb* were highly significantly correlated (r = 0.989 and 0.980, p < 0.001), and there were no significant differences between the two datasets (t test, p = 0.13 and 0.41; n = 42 and 17 for %RTL and Cb*, respectively). The reproducibilities of the %RTL and Cb* measurements (calculated in the photogrammetric case by taking photographs of the same macaques in two different environments) were significantly correlated between the datasets (r = 0.983 and 0.914, p < 0.001 and 0.005), and there were no significant differences between the datasets (t test, p = 0.539 and 0.344; n = 30 each for %RTL and Cb*, respectively). The %RTL and Cb* data were combined with data on the crown and cheek hair patterns and sex skin reddening of the macaques, and this combined data set was then analyzed by multiple correspondence analysis and agglomerative hierarchical cluster analysis, leading to the categorization of the rhesus macaques, long-tailed macaques, and hybrids at KKZ into five groups. Thus, photogrammetry can be utilized to identify macaque species or hybrids when species identification relies mainly on tail length and pelage color.

Assessment of pre-operative maropitant citrate use in macaque (Macaca fasicularis & Macaca mulatta) neurosurgical procedures.

PubMed

Steinbach, Jaclyn R; MacGuire, Jamus; Chang, Shu; Dierks, Elizabeth; Roble, Gordon S

2018-06-01

Retrospective analysis of post-operative vomiting (POV) in non-human primates at our institution was 11%. Based on this additional risk factor for post-operative complications, we aimed to eliminate or decrease POV by adding an antiemetic, maropitant citrate, to the pre-medication protocol. Retrospective and prospective data were collected over a 5-year period from 46 macaques of two species during 155 procedures. Additionally, blood was collected from five Macaca mulatta to perform a pharmacokinetic analysis. A 1 mg/kg subcutaneous dose of maropitant given pre-operatively significantly decreased POV. Findings indicated post-neurosurgical emesis in Macaca fasicularis was significantly greater than in Macaca mulatta. Pharmacokinetic analysis of maropitant in Macaca mulatta determined the mean maximum plasma concentration to be 113 ng/mL. Maropitant administration prior to anesthesia for neurosurgeries decreased our incidence of POV to 1%. The plasma concentration reaches the proposed plasma level for clinical efficacy approximately 20 minutes after administration. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

There Is More than One Way to Crack an Oyster: Identifying Variation in Burmese Long-Tailed Macaque (Macaca fascicularis aurea) Stone-Tool Use

PubMed Central

Tan, Amanda; Tan, Say Hoon; Vyas, Dhaval; Malaivijitnond, Suchinda; Gumert, Michael D.

2015-01-01

We explored variation in patterns of percussive stone-tool use on coastal foods by Burmese long-tailed macaques (Macaca fascicularis aurea) from two islands in Laem Son National Park, Ranong, Thailand. We catalogued variation into three hammering classes and 17 action patterns, after examining 638 tool-use bouts across 90 individuals. Hammering class was based on the stone surface used for striking food, being face, point, and edge hammering. Action patterns were discriminated by tool material, hand use, posture, and striking motion. Hammering class was analyzed for associations with material and behavioural elements of tool use. Action patterns were not, owing to insufficient instances of most patterns. We collected 3077 scan samples from 109 macaques on Piak Nam Yai Island’s coasts, to determine the proportion of individuals using each hammering class and action pattern. Point hammering was significantly more associated with sessile foods, smaller tools, faster striking rates, smoother recoil, unimanual use, and more varied striking direction, than were face and edge hammering, while both point and edge hammering were significantly more associated with precision gripping than face hammering. Edge hammering also showed distinct differences depending on whether such hammering was applied to sessile or unattached foods, resembling point hammering for sessile foods and face hammering for unattached foods. Point hammering and sessile edge hammering compared to prior descriptions of axe hammering, while face and unattached edge hammering compared to pound hammering. Analysis of scans showed that 80% of individuals used tools, each employing one to four different action patterns. The most common patterns were unimanual point hammering (58%), symmetrical-bimanual face hammering (47%) and unimanual face hammering (37%). Unimanual edge hammering was relatively frequent (13%), compared to the other thirteen rare action patterns (<5%). We compare our study to other stone

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

PubMed

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.

Optimization and Dose Estimation of Aerosol Delivery to Non-Human Primates.

PubMed

MacLoughlin, Ronan J; van Amerongen, Geert; Fink, James B; Janssens, Hettie M; Duprex, W Paul; de Swart, Rik L

2016-06-01

In pre-clinical animal studies, the uniformity of dosing across subjects and routes of administration is a crucial requirement. In preparation for a study in which aerosolized live-attenuated measles virus vaccine was administered to cynomolgus monkeys (Macaca fascicularis) by inhalation, we assessed the percentage of a nebulized dose inhaled under varying conditions. Drug delivery varies with breathing parameters. Therefore we determined macaque breathing patterns (tidal volume, breathing frequency, and inspiratory to expiratory (I:E) ratio) across a range of 3.3-6.5 kg body weight, using a pediatric pneumotachometer interfaced either with an endotracheal tube or a facemask. Subsequently, these breathing patterns were reproduced using a breathing simulator attached to a filter to collect the inhaled dose. Albuterol was nebulized using a vibrating mesh nebulizer and the percentage inhaled dose was determined by extraction of drug from the filter and subsequent quantification. Tidal volumes ranged from 24 to 46 mL, breathing frequencies from 19 to 31 breaths per minute and I:E ratios from 0.7 to 1.6. A small pediatric resuscitation mask was identified as the best fitting interface between animal and pneumotachometer. The average efficiency of inhaled dose delivery was 32.1% (standard deviation 7.5, range 24%-48%), with variation in tidal volumes as the most important determinant. Studies in non-human primates aimed at comparing aerosol delivery with other routes of administration should take both the inter-subject variation and relatively low efficiency of delivery to these low body weight mammals into account.

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

PubMed Central

Wareham, Alice; Lewandowski, Kuiama S.; Williams, Ann; Dennis, Michael J.; Sharpe, Sally; Vipond, Richard; Silman, Nigel; Ball, Graham

2016-01-01

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 comparisons

Nine-year mortality experience in proton-exposed Macaca mulatta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krupp, J.H.

1976-08-01

Macaca mulatta exposed at 2 yr of age to proton irradiation have been observed for mortality and latent effects since 1964. This report of progress covering the first 9 yr postexposure shows an interesting occurrence of neoplasia in the 55 MeV proton-exposed animals and an increased incidence of endometriosis in whole-body penetrating proton exposures. For doses of 400 rad and less, no significant deviation from control mortality is apparent, 9 yr postexposure.

Evaluation of a killed Rocky Mountain spotted fever vaccine in cynomolgus monkeys.

PubMed Central

Gonder, J C; Kenyon, R H; Pedersen, C E

1979-01-01

A nonhuman primate model of Rocky Mountain spotted fever infection was developed in cynomolgus monkeys (Macaca fascicularis) infected by the subcutaneous route or by aerosol. Clinical responses, hematology and serum chemistry values, and pathological findings were similar to those found in humans ill with Rocky Mountain spotted fever. The clinical model was then used to test the efficacy of a killed Rocky Mountain spotted fever vaccine grown in chicken embryo cells. Monkeys were immunized with varying dilutions of the vaccine with a two-dose schedule and then challenged at 2 months with virulent Rickettsia rickettsii by the subcutaneous route or by aerosol. The undiluted vaccine totally protected monkeys against both challenges, even at extremely high doses. PMID:120877

Ash content of bones in the pigtail monkey, Macaca nemestrina.

NASA Technical Reports Server (NTRS)

Vose, G. P.; Roach, T. L.

1972-01-01

Ash analyses of skeletons of four adult primates, Macaca nemestrina, revealed some similarities and some marked contrasts when compared with published data on human skeletal ash. The skull in both Macaca nemestrina and man has the highest ash content of all bones in the skeleton. While the bones of the arms of humans have an ash content nearly identical to that of the legs (0.3% difference), in Macaca nemestrina the humeri and radii contain 5.4% more ash than the femora and tibiae. Similarly in Macaca nemestrina the bones of the hands contain 3.5% more ash than the bones of the feet, while in humans the same bones agree within 0.3% implying that adaptive use function is a factor in bone ash concentration. The ribs of Macaca nemestrina showed an unexpectedly high ash content in comparison with those of humans. In contrast with the relatively constant ash content throughout the vertebrae in humans, a conspicuous decrease axially was noted in Macaca nemestrina.

Mechanical properties of the cement of the stalked barnacle Dosima fascicularis (Cirripedia, Crustacea)

PubMed Central

Zheden, Vanessa; Klepal, Waltraud; Gorb, Stanislav N.; Kovalev, Alexander

2015-01-01

The stalked barnacle Dosima fascicularis secretes foam-like cement, the amount of which usually exceeds that produced by other barnacles. When Dosima settles on small objects, this adhesive is additionally used as a float which gives buoyancy to the animal. The dual use of the cement by D. fascicularis requires mechanical properties different from those of other barnacle species. In the float, two regions with different morphological structure and mechanical properties can be distinguished. The outer compact zone with small gas-filled bubbles (cells) is harder than the interior one and forms a protective rind presumably against mechanical damage. The inner region with large, gas-filled cells is soft. This study demonstrates that D. fascicularis cement is soft and visco-elastic. We show that the values of the elastic modulus, hardness and tensile stress are considerably lower than in the rigid cement of other barnacles. PMID:25657833

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

PubMed Central

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

2016-01-01

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. PMID:27367733

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

PubMed

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.

Multidetector computed tomographic morphology of ovaries in cynomolgus macaques (Macaca fascicularis).

PubMed

Jones, Jeryl C; Appt, Susan E; Bourland, J Daniel; Hoyer, Patricia B; Clarkson, Thomas B; Kaplan, Jay R

2007-09-01

Macaques are important models for menopause and associated diseases in women. A sensitive, noninvasive technique for quantifying changes in ovarian morphology would facilitate longitudinal studies focused on the health-related sequelae of naturally occurring or experimentally induced alterations in ovarian structure and function. Multidetector computed tomography (MDCT) is a fast, non-invasive imaging technique that uses X-rays, multiple rows of detectors, and computers to generate detailed slice images of structures. The purpose of this study was to describe the utility of MDCT for reliably characterizing ovarian morphology in macaques. Five macaques were scanned using contrast-enhanced MDCT. The following characteristics were described: 1) appearance of ovaries and adjacent landmarks, 2) effects of varying technical protocols on ovarian image quality, 3) radiation doses delivered to the pelvic region during scanning, and 4) MDCT estimates of ovarian volume and antral follicle counts versus those measured directly in ovarian tissue. Ovaries were distinguishable in all MDCT scans and exhibited heterogeneous contrast enhancement. Antral follicles appeared as focal areas of nonenhancement. Ovarian image quality with 5 pediatric scanning protocols was sufficient for discriminating ovarian margins. Pelvic region radiation doses ranged from 0.5 to 0.7 rad. Antral follicles counted using MDCT ranged from 3 to 5 compared with 3 to 4 counted using histology. Ovarian volumes measured using MDCT ranged from 0.41 to 0.67 ml compared with 0.40 to 0.65 ml by water displacement. MDCT is a promising technique for measuring longitudinal changes in macaque ovarian morphology reliably and noninvasively.

Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta): a pharmacokinetic study.

PubMed

Bakker, J; Thuesen, L R; Braskamp, G; Skaanild, M T; Ouwerling, B; Langermans, J A M; Bertelsen, M F

2011-10-01

Cefovecin is a third-generation cephalosporin approved for antibacterial treatment with a 14-day dosing interval in dogs and cats. This antibiotic may also be useful for zoo and wildlife veterinary medicine, because of its broad spectrum and long duration of activity. The aim of the study was to determine whether cefovecin is a suitable antibiotic to prevent skin wound infection in rhesus monkeys. Therefore, the pharmacokinetics (PK) of cefovecin after a single subcutaneous injection at 8 mg/kg bodyweight in four rhesus monkeys (Macaca mulatta) and sensitivity of bacterial isolates from fresh skin wounds were determined. After administration, blood, urine, and feces were collected, and concentrations of cefovecin were determined. Further, the minimum inhibitory concentrations (MIC) for bacteria isolated from fresh skin wounds of monkeys during a health control program were determined. The mean maximum plasma concentration (C(max) ) of cefovecin was 78 μg/mL and was achieved after 57 min. The mean apparent long elimination half-life (t½) was 6.6 h and excretion occurred mainly via urine. The MIC for the majority of the bacteria examined was >100 μg/mL. The PK of cefovecin in rhesus monkeys is substantially different than for dogs and cats. Cefovecin rapidly reached C(max) which however was lower than most of the MIC levels and with a very short t½. Therefore, cefovecin is not recommended for treating skin wounds in rhesus monkeys. © 2011 Blackwell Publishing Ltd.

Evaluation of bendectin embryotoxicity in nonhuman primates: II. Double-blind study in term cynomolgus monkeys.

PubMed

Hendrickx, A G; Cukierski, M; Prahalada, S; Janos, G; Booher, S; Nyland, T

1985-10-01

The embryotoxic and teratogenic potential of Bendectin was assessed in this double-blind study in the cynomolgus monkey (Macaca fascicularis). Bendectin was administered orally at doses approximately two, five, and 20 times the human dose equivalent from 22 +/- 2 through 50 days of gestation. Fetuses were delivered by cesarean section near term and examined for malformations. There was no maternal toxicity as evidenced by maternal weights and physical signs. There was no correlation between dosage and the number of prenatal deaths. No significant abnormalities related to treatment were observed in postdelivery physical examinations, placental evaluations, external and internal gross examinations, or from radiographs of the neonates. Under the conditions of this study the treatment of pregnant cynomolgus monkeys with Bendectin produced no evidence of teratogenicity or embryo-, or fetal-, or maternal toxicity.

Macaque Monkeys Discriminate Pitch Relationships

ERIC Educational Resources Information Center

Brosch, Michael; Selezneva, Elena; Bucks, Cornelia; Scheich, Henning

2004-01-01

This study demonstrates that non-human primates can categorize the direction of the pitch change of tones in a sequence. Two "Macaca fascicularis" were trained in a positive-reinforcement behavioral paradigm in which they listened to sequences of a variable number of different acoustic items. The training of discriminating pitch direction was…

Effect of methylmercury on acetylcholinestrase and serum cholinesterase activity in monkeys, Macaca fascicularis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petruccioli, L.; Turillazzi, P.G.

1991-05-01

The consumption of fish and fish-derived products is the main pathway of human exposure to methylmercury (MeHg). Methylmercury levels vary widely in fish, depending on age, size, the position of the species in the food chain, and most of all, on pollution levels. MeHg affects the Acetylcholinesterase activity (AChE) and the serum Cholinesterase activity (BChE). Histoenzymatic studies showed that 100mg Methyoxyethylmercury chloride administered for 6 days to rats caused a reduction of AChE activity in the thalamus and an increase in different parts of the nervous central system. The present study aims at verifying whether the dose permitted by F.A.O.more » and doses 10 and 100 fold higher affect the Cholinesterase activity in primates, and whether there is a correlation between AChE and BChE.« less

Effects of Aroclor 1254 reg sign on hydrocortisone levels in adult Rhesus monkeys (Macaca mulatta)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loo, J.C.K.; Tryphonas, H.; Jordan, N.

Researchers, using female Sprague Dawley rats, reported the effects of chronic (5-7 months) oral dosing with Aroclor 1254{reg sign} (Polychlorinated biphenyls-PCB) on the serum levels of corticosterone, the principle glucocorticoid in rats. Their findings indicated that corticosterone levels were significantly depressed at dose levels of 479 {mu}g/kg bw/day and above. The objective of the present study was to determine the effects of PCB on the hydrocortisone levels in Rhesus monkey (Macaca mulatta) serum. In the monkey the controlling hormone is hydrocortisone which is identical to that of humans.

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

NASA Astrophysics Data System (ADS)

Deng, Liping; Zhu, Xiaobin; Su, Yingying; Su, Hua; Wang, Xinting

2008-02-01

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.

Infection of Macaca Radiata with Viruses of the Tick-Borne Encephalitis Group

DTIC Science & Technology

1992-01-01

3411 IC Microbial Patho genesis 1 992, 13: 399 409 ET AD-A265 505 N9 3U 9312898 I Infection of Macaca radiata with viruses of the tick - borne...Diseases, Frederick, MD 21702-5011, U.SA.), M. K. Rippy, K. T. McKee Jr., P. M. Zack and C. J. Peters. Infection of Macaca radiata with viruses of the tick ...for human disease caused by other, related strains of this group of viruses. Key words: Macaca radiata; tick -borne encephalitis; pathogenesis; Kyasanur

Allometry and Interspecific Differences in the Facial Cranium of Two Closely Related Macaque Species

PubMed Central

Ito, Tsuyoshi; Nishimura, Takeshi; Takai, Masanaru

2011-01-01

Interpreting evolutionary history of macaque monkeys from fossil evidence is difficult, because their evolutionary fluctuations in body size might have removed or formed important morphological features differently in each lineage. We employed geometric morphometrics to explore allometric trajectories of craniofacial shape in two closely related species, Macaca fascicularis and M. fuscata. These two species exhibit a single shared allometric trajectory in superoinferior deflection of the anterior face, indicating that the differences in this feature can be explained by size variation. In contrast, two parallel trajectories are demonstrated in craniofacial protrusion, indicating that even if they are comparable in size, M. fuscata has a higher and shorter face than M. fascicularis. The degree of facial protrusion is most likely a critical feature for phyletic evaluation in the fascicularis group. Such analyses in various macaques would help to resolve controversies regarding phyletic interpretations of fossil macaques. PMID:22567301

RNA-Seq Reveals Extensive Transcriptional Response to Heat Stress in the Stony Coral Galaxea fascicularis

PubMed Central

Hou, Jing; Xu, Tao; Su, Dingjia; Wu, Ying; Cheng, Li; Wang, Jun; Zhou, Zhi; Wang, Yan

2018-01-01

Galaxea fascicularis, a stony coral belonging to family Oculinidae, is widely distributed in Red Sea, the Gulf of Aden and large areas of the Indo-Pacific oceans. So far there is a lack of gene expression knowledge concerning this massive coral. In the present study, G. fascicularis was subjected to heat stress at 32.0 ± 0.5°C in the lab, we found that the density of symbiotic zooxanthellae decreased significantly; meanwhile apparent bleaching and tissue lysing were observed at 10 h and 18 h after heat stress. The transcriptome responses were investigated in the stony coral G. fascicularis during heat bleaching using RNA-seq. A total of 42,028 coral genes were assembled from over 439 million reads. Gene expressions were compared at 10 and 18 h after heat stress. The significantly upregulated genes found in the Control_10h vs. Heat_10h comparison, presented mainly in GO terms related with DNA integration and unfolded protein response; and for the Control_18h vs. Heat_18h comparison, the GO terms include DNA integration. In addition, comparison between groups of Control_10h vs. Heat_10h and Control_18h vs. Heat_18h revealed that 125 genes were significantly upregulated in common between the two groups, whereas 21 genes were significantly downregulated in common, all these differentially expressed genes were found to be involved in stress response, DNA integration and unfolded protein response. Taken together, our results suggest that high temperature could activate the stress response at the early stage, and subsequently induce the bleaching and lysing through DNA integration and unfolded protein response, which are able to disrupt the balance of coral-zooxanthella symbiosis in the stony coral G. fascicularis. PMID:29487614

Agreement of SpO2, SaO2 and ScO2 in anesthetized cynomolgus monkeys (Macaca fascicularis).

PubMed

Young, Simon S; Skeans, Susan M; Lamca, James E; Chapman, Richard W

2002-07-01

To assess the agreement between three measurements of arterial oxygen saturation (SpO 2 , SaO 2 and ScO 2 ) in anesthetized cynomolgus monkeys. Prospective study. Eleven mature, male cynomolgus monkeys (Macaca fasicularis). Monkeys were anesthetized with intramuscular ketamine followed by intravenous propofol. The trachea of each was intubated and the lungs ventilated. Arterial oxygen saturation was measured with a Nonin 8500 V pulse oximeter, using a lingual clip on the cheek. Arterial blood samples were taken from an indwelling catheter. Inspired oxygen concentration was varied from 12 to 20%, and 88 paired arterial blood samples and saturation measurements were taken. Arterial oxygen saturation in the blood samples was measured using a cooximeter. The saturation was also calculated from the arterial oxygen tension using the Adair equation. The results were compared using Bland and Altman's method. The pulse oximeter readings were 2.7% higher than that of the cooximeter, with a limit of agreement of -3.9 to 9.3%. The pulse oximeter readings were 1.8% higher than the calculated saturation, with a limit of agreement of -6.5% to 10.1%. The cooximeter readings were 0.9% lower than the calculated saturation, with a limit of agreement of -5.6% to 3.8%. The agreement between SpO 2 and other measurements of arterial oxygen saturation in this study is typical for this technique. The bias and limits of agreement are consistent with reports in other species. The Nonin 8500 V is a useful pulse oximeter for clinical use in primates. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.

PubMed

Grégoire, Laurent; Samadi, Pershia; Graham, Julie; Bédard, Paul J; Bartoszyk, Gerd D; Di Paolo, Thérèse

2009-07-01

Dyskinesia is an important complication of treatment in Parkinson's disease (PD). Sarizotan, a 5-HT(1A) agonist with high affinity for D3 and D4 receptors was investigated on L-Dopa-induced dyskinesia (LID) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. Five MPTP female cynomolgus monkeys (Macaca fascicularis) with a moderate to severe parkinsonian syndrome and LID were used. Sarizotan 0.2, 1, and 2 mg/kg administered alone did not worsen parkinsonian symptoms; there were no effect on locomotor counts or on normal behavior of the monkeys. Sarizotan 0.2, 1, and 2 mg/kg administered 30 min before a fixed dose of L-Dopa (25-30 mg/kg s.c.) + benserazide (50 mg) did not affect the antiparkinsonian response to L-Dopa. However, mean dyskinetic scores were significantly reduced with sarizotan 1 and 2 mg/kg but not at 0.2 mg/kg. Higher doses of sarizotan (4 and 8 mg/kg, administered immediately before L-Dopa) reduced L-Dopa-induced locomotor response in all monkeys. A pharmacokinetic investigation in these monkeys showed a dose-dependent increase in mean plasma sarizotan concentrations with similar mean plasma concentrations for sarizotan 1 mg/kg alone or with L-Dopa, indicating a lack of sarizotan/L-Dopa interaction. The time course of plasma sarizotan concentrations was associated with time of maximal reduction of dyskinesias. When administered daily for two weeks in combination with L-Dopa in the same MPTP monkeys, sarizotan 1 mg/kg had a sustained antidyskinetic effect while maintaining the antiparkinsonian and locomotor effect of L-Dopa. This detailed sarizotan investigation in MPTP monkeys supports the antidyskinetic activity of this drug and for 5-HT(1A) agonists.

Prototype Abstraction by Monkeys ("Macaca Mulatta")

ERIC Educational Resources Information Center

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…

Pediculosis in Macaca sylvanus of Gibraltar

PubMed Central

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

2007-01-01

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. PMID:17280788

Macaca specific exon creation event generates a novel ZKSCAN5 transcript.

PubMed

Kim, Young-Hyun; Choe, Se-Hee; Song, Bong-Seok; Park, Sang-Je; Kim, Myung-Jin; Park, Young-Ho; Yoon, Seung-Bin; Lee, Youngjeon; Jin, Yeung Bae; Sim, Bo-Woong; Kim, Ji-Su; Jeong, Kang-Jin; Kim, Sun-Uk; Lee, Sang-Rae; Park, Young-Il; Huh, Jae-Won; Chang, Kyu-Tae

2016-02-15

ZKSCAN5 (also known as ZFP95) is a zinc-finger protein belonging to the Krűppel family. ZKSCAN5 contains a SCAN box and a KRAB A domain and is proposed to play a distinct role during spermatogenesis. In humans, alternatively spliced ZKSCAN5 transcripts with different 5'-untranslated regions (UTRs) have been identified. However, investigation of our Macaca UniGene Database revealed novel alternative ZKSCAN5 transcripts that arose due to an exon creation event. Therefore, in this study, we identified the full-length sequences of ZKSCAN5 and its alternative transcripts in Macaca spp. Additionally, we investigated different nonhuman primate sequences to elucidate the molecular mechanism underlying the exon creation event. We analyzed the evolutionary features of the ZKSCAN5 transcripts by reverse transcription polymerase chain reaction (RT-PCR) and genomic PCR, and by sequencing various nonhuman primate DNA and RNA samples. The exon-created transcript was only detected in the Macaca lineage (crab-eating monkey and rhesus monkey). Full-length sequence analysis by rapid amplification of cDNA ends (RACE) identified ten full-length transcripts and four functional isoforms of ZKSCAN5. Protein sequence analyses revealed the presence of two groups of isoforms that arose because of differences in start-codon usage. Together, our results demonstrate that there has been specific selection for a discrete set of ZKSCAN5 variants in the Macaca lineage. Furthermore, study of this locus (and perhaps others) in Macaca spp. might facilitate our understanding of the evolutionary pressures that have shaped the mechanism of exon creation in primates. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

PubMed

Kuno, S; Mizuta, E; Nishida, J; Takechi, M

1992-10-01

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

Pulmonary cestodiasis in a cynomolgus monkey (Macaca fascicularis).

PubMed

Guillot, L M; Green, L C

1992-04-01

Cestodiasis in primates has been noted historically to occur quite frequently, although tissue damage and clinical signs may or may not be apparent. Larval cestodes, such as hydatid cysts or cysticercus cysts, are known to cause extensive tissue damage, while other larval cestodes, such as tetrathyridia, cause minimal damage to the host. This case history concerns an apparently healthy cynomolgus monkey that was part of a surgical study. During the study, all parameters were normal. The monkey died 3 hours postsurgery. The apparent cause of death was respiratory arrest. At necropsy, it was discovered there were 1- to 3-mm-diameter cysts, which on transection extruded 2- to 5-mm-long larvae. The larvae could not be positively identified; however, they resembled tetrathyridia of Mesocestoides sp.

Ecology of malaria parasites infecting Southeast Asian macaques: evidence from cytochrome b sequences

PubMed Central

Putaporntip, Chaturong; Jongwutiwes, Somchai; Thongaree, Siriporn; Seethamchai, Sunee; Grynberg, Priscila; Hughes, Austin L.

2010-01-01

Although malaria parasites infecting non-human primates are important models for human malaria, little is known of the ecology of infection by these parasites in the wild. We extensively sequenced cytochrome b (cytb) of malaria parasites (Apicomplexa: Haemosporida) from free-living Southeast Asian monkeys Macaca nemestrina and M. fascicularis. The two most commonly observed taxa were P. inui and Hepatocystis sp., but certain other sequences did not cluster closely with any previously sequenced species. Most of the major clades of parasites were found in both Macaca species; and the two most commonly occurring parasite infected the two Macaca species at approximately equal levels. However, P. inui showed evidence of genetic differentiation between the populations infecting the two Macaca species, suggesting limited movement of this parasite among hosts. Moreover, coinfection with Plasmodium and Hepatocystis species occurred significantly less frequently than expected on the basis of the rates of infection with either taxon alone, suggesting the possibility of competitive exclusion. The results revealed unexpectedly complex communities of Plasmodium and Hepatocystis taxa infecting wild Southeast Asian monkeys. Parasite taxa differed with respect to both the frequency of between-host movement and their frequency of coinfection. PMID:20646216

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

PubMed Central

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

Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive.

PubMed

O'Rand, Michael G; Hamil, Katherine G; Adevai, Tiffany; Zelinski, Mary

2018-01-01

Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75-80 mg/kg) followed by a recovery period and a subsequent high dose (125-130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.

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

PubMed Central

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

2014-01-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5 mg/kg bw) or NaOCN (50 mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~ 80X faster in the nervous system (14 milliseconds to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In macaca fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~ 2X relative to that of rodents. The nervous system susceptibility to cyanide may result from a “multiple hit” by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. PMID:24500607

Persistent infection of rhesus monkeys with 'Helicobacter macacae' and its isolation from an animal with intestinal adenocarcinoma.

PubMed

Marini, Robert P; Muthupalani, Sureshkumar; Shen, Zeli; Buckley, Ellen M; Alvarado, Cynthia; Taylor, Nancy S; Dewhirst, Floyd E; Whary, Mark T; Patterson, Mary M; Fox, James G

2010-08-01

A novel helicobacter, 'Helicobacter macacae', was previously isolated from a colony of rhesus and cynomolgus monkeys in which diarrhoea from chronic idiopathic colitis was enzootic. A survey performed in a second colony of rhesus monkeys without a history of chronic diarrhoea determined that 57 % were faecal-culture positive for Helicobacter species. Ten years after the survey, one of the animals from which 'H. macacae' had been isolated, a 23-year-old, intact male rhesus monkey (Macaca mulatta), presented with partial inappetence and progressive weight loss. Subsequent evaluation of the monkey revealed anaemia, hypoproteinaemia, hypoalbuminaemia and a palpable abdominal mass. Contrast radiography suggested partial intestinal obstruction. The animal was euthanized and a diagnosis was made of intestinal adenocarcinoma of the ileocaecocolic junction with metastasis to regional lymph nodes and liver. Microaerobic culture of caecal tissue yielded a helicobacter organism identified as 'H. macacae' by 16S rRNA gene sequencing - the same species of bacteria isolated 10 years previously. The liver, small intestine and colon were also positive by PCR for Helicobacter species. Intestinal adenocarcinoma is the most common malignancy of aged macaques. Faeces or caecal tissue from five out of five monkeys that remained from the original cohort and that were colonized with 'H. macacae' in the initial survey were positive for the organism. The apparent persistence of 'H. macacae' in these animals, the isolation of the bacterium from animals with colitis and the recognition of the importance of inflammation in carcinogenesis raise the possibility of an aetiological role in the genesis of intestinal adenocarcinoma in aged rhesus monkeys.

Cycloartane triterpenes from marine green alga Cladophora fascicularis

NASA Astrophysics Data System (ADS)

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.

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

PubMed

Ballesta, Sébastien; Reymond, Gilles; Pozzobon, Matthieu; Duhamel, Jean-René

2016-01-01

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.

Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys.

PubMed

Tsarev, S A; Tsareva, T S; Emerson, S U; Yarbough, P O; Legters, L J; Moskal, T; Purcell, R H

1994-06-01

The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive. The infectivity titer of SAR-55 was 10(6) cynomolgus 50% infectious doses per gram of feces. The infectivity titer corresponded to the HEV genome titer of the inoculum as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HEV IgM was detected in only a portion of the animals that had an anti-HEV IgG response. Biochemical evidence of hepatitis was most prominent in animals that were inoculated with the higher concentrations of virus and the incubation period to seroconversion was prolonged in animals that received the lower doses.

Spectral sensitivity of cones of the monkey Macaca fascicularis.

PubMed Central

Baylor, D A; Nunn, B J; Schnapf, J L

1987-01-01

1. Spectral sensitivities of cones in the retina of cynomolgus monkeys were determined by recording photocurrents from single outer segments with a suction electrode. 2. The amplitude and shape of the response to a flash depended upon the number of photons absorbed but not the wave-length, so that the 'Principle of Univariance' was obeyed. 3. Spectra were obtained from five 'blue', twenty 'green', and sixteen 'red' cones. The wave-lengths of maximum sensitivity were approximately 430, 531 and 561 nm, respectively. 4. The spectra of the three types of cones had similar shapes when plotted on a log wave number scale, and were fitted by an empirical expression. 5. There was no evidence for the existence of subclasses of cones with different spectral sensitivities. Within a class, the positions of the individual spectra on the wave-length axis showed a standard deviation of less than 1.5 nm. 6. Psychophysical results on human colour matching (Stiles & Burch, 1955; Stiles & Burch, 1959) were well predicted from the spectral sensitivities of the monkey cones. After correction for pre-retinal absorption and pigment self-screening, the spectra of the red and green cones matched the respective pi 5 and pi 4 mechanisms of Stiles (1953, 1959). PMID:3443931

Establishment and characterization of Macaca fascicularis lymphoblastoid cell lines.

PubMed

Manning, C H; Heise, E R

1992-01-01

A panel of cynomolgus macaque lymphoblastoid cell lines (LCL) was established by transforming peripheral blood mononuclear cells (PBMC) with Herpesvirus papio (HVP), and selected lines were examined by flow cytometry. Results indicate that HVP-transformed macaque LCL are phenotypically heterogeneous and resemble human Epstein-Barr virus (EBV)-transformed LCL in the abundant expression of major histocompatibility complex (MHC) class I and class II molecules. At least some lines are of B cell origin.

Tissue enzyme studies in Macaca nemestrina monkeys.

NASA Technical Reports Server (NTRS)

Hubbard, R. W.; Hoffman, R. A.; Jenkins, D.

1971-01-01

Total enzyme activities in fresh tissue specimens from major organs of Macaca nemestrina were analyzed for lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and aldolase. The concentration of these enzymes varied among the different tissue with skeletal muscle, heart, and brain having the highest activities. LDH isozymes determinations for the various tissues were also made. The spectrum of LDH isozyme distribution appears to be quite specific and characteristic for at least some of the tissues analyzed.

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

PubMed Central

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

2017-01-01

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. PMID:28181581

76 FR 677 - Requirements for Importers of Nonhuman Primates

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

...CDC is proposing to amend its regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs. Filovirus testing will continue to be required only for Old World NHPs. CDC also is proposing to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their registrations, (from every 180 days to every two years). CDC proposes to incorporate existing guidelines into the regulations and add new provisions to address: NHPs imported as part of a trained animal act; NHPs imported or transferred by zoological societies; The transfer of NHPs from approved laboratories; and Non-live imported NHP products. CDC is also proposing that all NHPs be imported only through ports of entry where a CDC quarantine station is located.

Macaques at the margins: the biogeography and extinction of Macaca sylvanus in Europe

NASA Astrophysics Data System (ADS)

Elton, Sarah; O'Regan, Hannah J.

2014-07-01

The genus Macaca (Primates: Cercopithecidae) originated in Africa, dispersed into Europe in the Late Miocene and resided there until the Late Pleistocene. In this contribution, we provide an overview of the evolutionary history of Macaca in Europe, putting it into context with the wider late Miocene, Pliocene and Pleistocene European monkey fossil record (also comprising Mesopithecus, Paradolichopithecus, Dolichopithecus and Theropithecus). The Pliocene and Pleistocene European Macaca fossil material is largely regarded as Macaca sylvanus, the same species as the extant Barbary macaque in North Africa. The M. sylvanus specimens found at West Runton in Norfolk (53°N) during the Middle Pleistocene are among the most northerly euprimates ever discovered. Our simple time-budget model indicates that short winter day lengths would have imposed a significant constraint on activity at such relatively high latitudes, so macaque populations in Britain may have been at the limit of their ecological tolerance. Two basic models using climatic and topographic data for the Last Interglacial and the Last Glacial Maximum alongside Middle and Late Pleistocene fossil distributions indicate that much of Europe may have been suitable habitat for macaques. The models also indicate that areas of southern Europe in the present day have a climate that could support macaque populations. However, M. sylvanus became locally extinct in the Late Pleistocene, possibly at a similar time as the straight-tusked elephant, Palaeoloxodon antiquus, and narrow-nosed rhinoceros, Stephanorhinus hemitoechus. Its extinction may be related to vegetation change or increased predation from Homo, although other factors (such as stochastic factors occurring as a result of small population sizes) cannot be ruled out. Notwithstanding the cause of extinction, the European macaque may thus be a previously overlooked member of the Late Pleistocene faunal turnover.

Thermal regulation in Macaca mulatta during space flight

NASA Technical Reports Server (NTRS)

Klimovitsky, V. Y.; Alpatov, A. M.; Hoban-Higgins, T. M.; Utekhina, E. S.; Fuller, C. A.

2000-01-01

The results of studies of body temperature and thermal regulation in Macaca mulatta flown on biosatellites Bion 6-11 are presented. The effect of microgravity on deep body temperature as compared to skin temperature was investigated. In most animals, deep body temperature declined moderately and then tended to return to normal. Brain temperature/ankle temperature correlation changed. The system of thermal regulation was found to function adequately in space.

West Nile Virus Encephalitis in a Barbary Macaque (Macaca sylvanus)

PubMed Central

Barker, Ian K.; Crawshaw, Graham J.; Bertelsen, Mads F.; Drebot, Michael A.; Andonova, Maya

2004-01-01

An aged Barbary ape (Macaca sylvanus) at the Toronto Zoo became infected with naturally acquired West Nile virus (WNV) encephalitis that caused neurologic signs, which, associated with other medical problems, led to euthanasia. The diagnosis was based on immunohistochemical assay of brain lesions, reverse transcriptase–polymerase chain reaction, and virus isolation. PMID:15200866

Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis.

PubMed

Huang, Xinping; Li, Min; Xu, Bo; Zhu, Xiaobin; Deng, Zhiwei; Lin, Wenhan

2007-03-21

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-alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

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

NASA Technical Reports Server (NTRS)

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.

Tracking cells implanted into cynomolgus monkeys (Macaca fascicularis) using MRI

PubMed Central

Ito-Fujishiro, Yasuyo; Koie, Hiroshi; Shibata, Hiroaki; Okabayashi, Sachi; Katakai, Yuko; Ohno, Chieko; Kanayama, Kiichi; Yasutomi, Yasuhiro; Ageyama, Naohide

2016-01-01

Regenerative therapy with stem cell transplantation is used to treat various diseases such as coronary syndrome and Buerger’s disease. For instance, stem-cell transplantation into the infarcted myocardium is an innovative and promising strategy for treating heart failure due to ischemic heart disease. Basic studies using small animals have shown that transplanted cells improve blood flow in the infarcted region. Magnetic resonance imaging (MRI) can noninvasively identify and track transplanted cells labeled with superparamagnetic iron oxide (SPIO). Although clinical regenerative therapies have been clinically applied to patients, the fate of implanted cells remains unknown. In addition, follow-up studies have shown that some adverse events can occur after recovery. Therefore, the present study evaluated the ability of MRI using a 3T scanner to track implanted peripheral blood mononuclear cells labeled with SPIO on days 0 and 7 after intramuscular (i.m.) and intravenous (i.v.) injection into a cynomolgus monkey. Labeled cells were visualized at the liver and triceps surae muscle on MR images using T1- and T2-weighted sequences and histologically localized by Prussian blue staining. The transplanted cells were tracked without abnormal clinical manifestations throughout this study. Hence, MRI of cynomolgus monkey transplanted SPIO-labeled cells is a safe and efficient method of tracking labeled cells that could help to determine the mechanisms involved in regenerative therapy. PMID:27062993

Energy metabolism of Macaca mulatta during spaceflight

NASA Technical Reports Server (NTRS)

Hoban-Higgins, T. M.; Stein, T. P.; Dotsenko, M. A.; Korolkov, V. I.; Fuller, C. A.

2000-01-01

The mean daily energy expenditure rates of two rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint U.S./Russian Bion 11 mission by the doubly labeled water (DLW, 2H218O) method. Control values were obtained from two studies performed under flight-like conditions (n = 4). The mean inflight energy expenditure for the two Bion 11 monkeys was 81.3 kcal/kg/day, which was higher than that seen previously. The average energy expenditure (77.6 +/- 4.4 kcal/kg/day) for the four ground control monkeys was slightly lower than had been measured previously.

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

ERIC Educational Resources Information Center

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…

Interactive effects of oxygen, carbon dioxide and flow on photosynthesis and respiration in the scleractinian coral Galaxea fascicularis.

PubMed

Osinga, Ronald; Derksen-Hooijberg, Marlous; Wijgerde, Tim; Verreth, Johan A J

2017-06-15

Rates of dark respiration and net photosynthesis were measured for six replicate clonal fragments of the stony coral Galaxea fascicularis (Linnaeus 1767), which were incubated under 12 different combinations of dissolved oxygen (20%, 100% and 150% saturation), dissolved carbon dioxide (9.5 and 19.1 µmol l -1 ) and water flow (1-1.6 versus 4-13 cm s -1 ) in a repeated measures design. Dark respiration was enhanced by increased flow and increased oxygen saturation in an interactive way, which relates to improved oxygen influx into the coral tissue. Oxygen saturation did not influence net photosynthesis: neither hypoxia nor hyperoxia affected net photosynthesis, irrespective of flow and pH, which suggests that hyperoxia does not induce high rates of photorespiration in this coral. Flow and pH had a synergistic effect on net photosynthesis: at high flow, a decrease in pH stimulated net photosynthesis by 14%. These results indicate that for this individual of G. fascicularis , increased uptake of carbon dioxide rather than increased efflux of oxygen explains the beneficial effect of water flow on photosynthesis. Rates of net photosynthesis measured in this study are among the highest ever recorded for scleractinian corals and confirm a strong scope for growth. © 2017. Published by The Company of Biologists Ltd.

Abdominal cysticercosis in a rhesus macaque (Macaca mulatta).

PubMed

Hobbs, Theodore R; Colgin, Lois M A; Maginnis, Gwendalyn M; Lewis, Anne D

2003-10-01

A mid-abdominal mass was discovered during routine physical examination of a rhesus macaque (Macaca mulatta). Further diagnostics and exploratory laparotomy were performed, revealing a fluid-filled cyst attached to the caudal free margin of the greater omentum. Formation and pulsatile movement of white-colored circumferential bands within the wall of the cyst were observed during surgery. The cyst was removed and later was dissected. The discovery of a single invaginated scolex identified the cyst as a cysticercus. The location and characteristics of the cysticercus were consistent with the larval form of Taenia hydatigena.

Effect of vaccination schedule on immune response of Macaca mulatta to cell culture-grown Rocky Mountain spotted fever vaccine.

PubMed Central

Sammons, L S; Kenyon, R H; Pedersen, C E

1976-01-01

The effect of vaccination schedule on the immune response of Macaca mulatta to formalin-inactivated chicken embryo cell culture (CEC)-grown Rickettsia rickettsii vaccine was studied. Schedules consisted of inoculation on day 1 only, on days 1 and 15, on days 1 and 30, on days 1, 8, and 15, or on days 1, 15, and 45. Humoral antibody measured by microagglutination and indirect immunofluorescence and resistance to challenge with 10(4) plaque-forming units of yolk sac-grown R. rickettsii were assessed. Seroconversion was noted in all monkeys after the first dose of vaccine. A second dose administered 8 or 15 days after the primary infection, or a third given 7 or 30 days after the second, produced no long-term effect on antibody titer. Only monkeys given two doses of vaccine at a 30-day interval showed an increase in antibody titer during the period before challenge. Vaccination with one, two, or three doses of CEC vaccine prevented development of rash and rickettsemia after challenge. The two-dose schedules appeared to induce the highest degree of resistance to challenge, as indicated by unaltered hematological parameters and body temperature in monkeys. The one- and three-dose schedules were somewhat less effective, in that some challenged monkeys within each group displayed febrile and leukocyte responses associated with Rocky Mountain spotted fever infection. Our data suggest that administration of two doses of CEC vaccine at 15- or 30-day intervals is the immunization schedule of choice. PMID:823173

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

PubMed

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.

Standardization of magnetocardiography in nonhuman primates

NASA Astrophysics Data System (ADS)

Seki, Yusuke; Muneyuki, Kenta; Kandori, Akihiko; Tsukada, Keiji; Terao, Keiji; Ageyama, Naohide

2008-03-01

To establish the electrophysiological mappings of nonhuman primates by using magnetocardiogram (MCG) data and obtain the normal values of MCG parameters, we used 64-channel superconducting quantum interference devices to measure 8 × 8 MCG data for 95 cynomolgus monkeys (Macaca fascicularis, 51 female and 44 male). The PQ interval, QRS duration, QT interval and QTc were respectively 79 ± 14 ms, 42 ± 7 ms, 222 ± 23 ms and 363 ± 25 (mean ± SD), and these parameters did not differ significantly between female and male monkeys. These results indicate the normal values of the MCG parameters of the cynomolgus monkey and should facilitate animal experiments in magnetocardiography.

The colonization of carrion by soldier fly, Ptecticus melanurus (Walker) (Diptera: Stratiomyidae) in a tropical forest in Malaysia: a new potential species for minimum PMI estimation.

PubMed

Azwandi, A; Omar, B

2012-12-01

This paper discusses the colonization of the stratiomyid species Ptecticus melanurus (Walker) (Diptera: Stratiomyidae) in monkey carrion and its potential for the determination of the minimum time since death (PMI). A study was conducted in a tropical forest at Bangi, Malaysia from 13 November 2009 to 8 June 2011. Twelve monkey carcasses (Macaca fascicularis Raffles) were used and divided in equal number into three different field trials. Adults of P. melanurus were first observed on monkey carrions on the second day the carcasses were placed in the field while their penultimate instar larvae were found in the wet soil under and beside carcass from day 8 to 31 days postmortem.

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

PubMed Central

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

2005-01-01

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 ≈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. PMID:15870193

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

PubMed

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

2012-12-17

Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n=12). Local reactions were observed at the administration site of four treated animals (n=6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

DTIC Science & Technology

2010-09-01

and interstitial fibrosis, and fibrous pleural adhesions. Other lesions included lymphoid hyperplasia and plasmacytosis, and chronic periadnexal and...inflammation in the lung and mediastinal lymph nodes, chronic inflammation centered on bronchi and vessels, type II pneumocyte hyperplasia , pleural...2/6 33 1/6 16 1/3 33 spleen splenitis, necrotizing 1/3 33 2/6 33 4/6 66 2/3 66 lymphoid depletion 2/3 66 3/6 50 3/6 50 2/3 66 lymphoid hyperplasia * 0

Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis).

PubMed

Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

2016-01-01

To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status.

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

DTIC Science & Technology

1990-05-01

generation of tetanus-specific antibody, producing B cells after in vivo immunization of Crohn’s dis- ease and ulcerative colitis patients ...lty Codes APPROVED: Noat eoa Sanford Millef, Ph.D. Dean CON;’ DEDICATION 1 his thesis is dedicated to the ones who so patiently tucked away their...were expermentally infected with Brugia milayi, a human filarial parasite , and antibody levels followed by enzyme linked immunosorbant assay (ELISA

Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

2016-01-01

To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status. PMID:27657707

Video-induced yawning in stumptail macaques (Macaca arctoides)

PubMed Central

Paukner, Annika; Anderson, James R

2005-01-01

This study reports the first experimental exploration of possible contagious yawning in monkeys. Twenty-two stumptail macaques (Macaca arctoides) were presented with video clips of either yawns or control mouth movements by conspecifics. At a group level, monkeys yawned significantly more often during and just after the yawn tape than the control tape. Supplementary analysis revealed that the yawn tape also elicited significantly more self-directed scratching responses than the control tape, which suggests that yawning might have been caused by tension arising from viewing the yawn tape. Understanding to what extent the observed effect resembles contagious yawning as found in humans and chimpanzees requires more detailed experimentation. PMID:17148320

The vocal repertoire of Tibetan macaques (Macaca thibetana): A quantitative classification.

PubMed

Bernstein, Sofia K; Sheeran, Lori K; Wagner, R Steven; Li, Jin-Hua; Koda, Hiroki

2016-09-01

Vocal repertoires are basic and essential components for describing vocal communication in animals. Studying the entire suite of vocal signals aids investigations on the variation of acoustic structure across social contexts, comparisons on the complexity of communication systems across taxa, and in exploration of the evolutionary origins of species-specific vocalizations. Here, we describe the vocal repertoire of the largest species in the macaque genus, Macaca thibetana. We extracted thirty acoustic parameters from call recordings. Post hoc validation through quantitative analyses of the a priori repertoire classified eleven call types: coo, squawk, squeal, noisy scream, growl, bark, compound squeak, leap coo, weeping, modulated tonal scream, and pant. In comparison to the rest of the genus, Tibetan macaques uttered a wider array of vocalizations in the context of copulations. Previous reports did not include modulated tonal screams and pants during harassment of copulatory dyads. Furthermore, in comparison to the rest of the genus, Tibetan macaque females emit acoustically distinct copulation calls. The vocal repertoire of Tibetan macaques contributes to the literature on the emergence of species-specific calls in the genus Macaca with potential insights from social, reproductive, and ecological comparisons across species. Am. J. Primatol. 78:937-949, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Can Monkeys (Macaca mulatta) Represent Invisible Displacement?

NASA Technical Reports Server (NTRS)

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.

EFFECTS OF PCB (AROCLORR 1254) ON NON-SPECIFIC IMMUNE PARAMETERS IN RHESUS (MACACA MULATA) MONKEYS.

EPA Science Inventory

The effects of low level chronic polychlorinated biphenyl - Aroclor 1254 - (PCB) exposure were investigated on nonspecific immune parameters in female rhesus (Macaca mulatta) monkeys. Five groups of monkeys were orally administered PCB at concentrations of 0, 5, 20, 40, or 80 ug/...

Using stereotactic brain atlases for small rodents and nonhuman primates for optrode array customization

NASA Astrophysics Data System (ADS)

Boutte, Ronald W.; Merlin, Sam; Griffiths, Brandon; Parry, Trent; Blair, Steve

2017-02-01

As the optogenetic field expands its need to target with high specificity only grows more crucial. This work will show a method for customizing soda-lime glass optrode arrays so that fine structures within the brains of small rodents and nonhuman primates can be optically interrogated below the outer cortical layer. An 8 × 6 array is customized for optrode length (400 μm ), optrode width (75 μm ), optrode pitch (400 μm ), backplane thickness (500 μm ), and overall form factor (3.45 mm × 2.65 mm ). The 400 μm long optrode is capable of illuminating the cortical Layer IV of rhesus macaque ( Macaca Fascicularis ) and the motor cortex of small mice ( Mus Musculus ).

Sorption and desorption of lead (II) from wastewater by green algae Cladophora fascicularis.

PubMed

Deng, Liping; Su, Yingying; Su, Hua; Wang, Xinting; Zhu, Xiaobin

2007-05-08

Biosorption is an effective method to remove heavy metals from wastewater. In this work, adsorption features of Cladophora fascicularis were investigated as a function of time, initial pH, initial Pb(II) concentrations, temperature and co-existing ions. Kinetics and equilibria were obtained from batch experiments. The biosorption kinetics followed the pseudo-second order model. Adsorption equilibria were well described by the Langmuir and Freundlich isotherm models. The maximum adsorption capacity was 198.5 mg/g at 298K and pH 5.0. The adsorption processes were endothermic and the biosorption heat was 29.6 kJ/mol. Desorption experiments indicated that 0.01 mol/L Na(2)EDTA was an efficient desorbent for the recovery of Pb(II) from biomass. IR spectrum analysis suggested amido or hydroxy, CO and C-O could combine intensively with Pb(II).

Retinal, functional, and morphological comparisons of two different macaque species, Macaca mulatta and Macaca fasicularis, for models of laser eye injury

NASA Astrophysics Data System (ADS)

DiCarlo, Cheryl D.; Hacker, Henry D.; Brown, Araceli; Cheramie, Rachael; Martinsen, Gary L.; Rockwell, Benjamin; Stuck, Bruce E.

2005-04-01

The past several years has seen a severe shortage of pathogen-free Indian origin rhesus macaques due to the increased requirement for this model in retroviral research. With greater than 30 years of research data accumulated using the Rhesus macaque as the model for laser eye injury there exists a need to bridge to a more readily available nonhuman primate model. Much of the data previously collected from the Rhesus monkey (Macaca mulatta) provided the basis for the American National Standards Institute (ANSI) standards for laser safety. Currently a Tri-service effort is underway to utilize the Cynomolgus monkey (Macaca fasicularis) as a replacement for the Rhesus macaque. Preliminary functional and morphological baseline data collected from multifocal electroretinography (mfERG), optical coherence tomography (OCT) and retinal cell counts were compared from a small group of monkeys and tissues to determine if significant differences existed between the species. Initial functional findings rom mfERG yielded only one difference for the n2 amplitude value which was greater in the Cynomolgus monkey. No significant differences were seen in retinal and foveal thickness, as determined by OCT scans and no significant differences were seen in ganglion cell and inner nuclear cell nuclei counts. A highly significant difference was seen in the numbers of photoreceptor nuclei with greater numbers in the Rhesus macaque. This indicates more studies should be performed to determine the impact that a model change would have on the laser bioeffects community and their ability to continue to provide minimal visible lesion data for laser safety standards. The continued goal of this project will be to provide that necessary baseline information for a seamless transition to a more readily available animal model.

Validation of multi-detector computed tomography as a non-invasive method for measuring ovarian volume in macaques (Macaca fascicularis).

PubMed

Jones, Jeryl C; Appt, Susan E; Werre, Stephen R; Tan, Joshua C; Kaplan, Jay R

2010-06-01

The purpose of this study was to validate low radiation dose, contrast-enhanced, multi-detector computed tomography (MDCT) as a non-invasive method for measuring ovarian volume in macaques. Computed tomography scans of four known-volume phantoms and nine mature female cynomolgus macaques were acquired using a previously described, low radiation dose scanning protocol, intravenous contrast enhancement, and a 32-slice MDCT scanner. Immediately following MDCT, ovaries were surgically removed and the ovarian weights were measured. The ovarian volumes were determined using water displacement. A veterinary radiologist who was unaware of actual volumes measured ovarian CT volumes three times, using a laptop computer, pen display tablet, hand-traced regions of interest, and free image analysis software. A statistician selected and performed all tests comparing the actual and CT data. Ovaries were successfully located in all MDCT scans. The iliac arteries and veins, uterus, fallopian tubes, cervix, ureters, urinary bladder, rectum, and colon were also consistently visualized. Large antral follicles were detected in six ovaries. Phantom mean CT volume was 0.702+/-SD 0.504 cc and the mean actual volume was 0.743+/-SD 0.526 cc. Ovary mean CT volume was 0.258+/-SD 0.159 cc and mean water displacement volume was 0.257+/-SD 0.145 cc. For phantoms, the mean coefficient of variation for CT volumes was 2.5%. For ovaries, the least squares mean coefficient of variation for CT volumes was 5.4%. The ovarian CT volume was significantly associated with actual ovarian volume (ICC coefficient 0.79, regression coefficient 0.5, P=0.0006) and the actual ovarian weight (ICC coefficient 0.62, regression coefficient 0.6, P=0.015). There was no association between the CT volume accuracy and mean ovarian CT density (degree of intravenous contrast enhancement), and there was no proportional or fixed bias in the CT volume measurements. Findings from this study indicate that MDCT is a valid non

Characterization of cement float buoyancy in the stalked barnacle Dosima fascicularis (Crustacea, Cirripedia).

PubMed

Zheden, Vanessa; Kovalev, Alexander; Gorb, Stanislav N; Klepal, Waltraud

2015-02-06

Dosima fascicularis is the only barnacle which can drift autonomously at the water surface with a foam-like cement float. The cement secreted by the animal contains numerous gas-filled cells of different size. When several individuals share one float, their size and not their number is crucial for the production of both volume and mass of the float. The gas content within the cells of the foam gives positive static buoyancy to the whole float. The volume of the float, the gas volume and the positive static buoyancy are positively correlated. The density of the cement float without gas is greater than that of seawater. This study shows that the secreted cement consists of more than 90% water and the gas volume is on average 18.5%. Our experiments demonstrate that the intact foam-like cement float is sealed to the surrounding water.

Characterization of cement float buoyancy in the stalked barnacle Dosima fascicularis (Crustacea, Cirripedia)

PubMed Central

Zheden, Vanessa; Kovalev, Alexander; Gorb, Stanislav N.; Klepal, Waltraud

2015-01-01

Dosima fascicularis is the only barnacle which can drift autonomously at the water surface with a foam-like cement float. The cement secreted by the animal contains numerous gas-filled cells of different size. When several individuals share one float, their size and not their number is crucial for the production of both volume and mass of the float. The gas content within the cells of the foam gives positive static buoyancy to the whole float. The volume of the float, the gas volume and the positive static buoyancy are positively correlated. The density of the cement float without gas is greater than that of seawater. This study shows that the secreted cement consists of more than 90% water and the gas volume is on average 18.5%. Our experiments demonstrate that the intact foam-like cement float is sealed to the surrounding water. PMID:25657839

Control of communicable disease; foreign--requirements for importers of nonhuman primates (NHP). Final rule.

PubMed

2013-02-15

The Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS), is amending regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs with the exception of the filovirus testing requirement. Filovirus testing will only be required for Old World NHPs in quarantine that have illness consistent with filovirus infection or that die for any reason other than trauma during quarantine. HHS/CDC is also finalizing a provision to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their special permits (from every 180 days to every 2 years). HHS/CDC is incorporating existing guidelines into the regulations and adding new provisions to address the following: NHPs imported as part of an animal act; NHPs imported or transferred by zoological societies; the transfer of NHPs from approved laboratories; and non-live imported NHP products. Finally, HHS/CDC is also requiring that all NHPs be imported only through ports of entry where a HHS/CDC quarantine station is located.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

...The Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS), is amending regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs with the exception of the filovirus testing requirement. Filovirus testing will only be required for Old World NHPs in quarantine that have illness consistent with filovirus infection or that die for any reason other than trauma during quarantine. HHS/CDC is also finalizing a provision to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their special permits (from every 180 days to every 2 years). HHS/CDC is incorporating existing guidelines into the regulations and adding new provisions to address the following: NHPs imported as part of an animal act; NHPs imported or transferred by zoological societies; the transfer of NHPs from approved laboratories; and non-live imported NHP products. Finally, HHS/CDC is also requiring that all NHPs be imported only through ports of entry where a HHS/CDC quarantine station is located.

Evaluation of Macaca mulatta as a model for genotoxicity studies.

PubMed

Dobrovolsky, Vasily N; Shaddock, Joseph G; Mittelstaedt, Roberta A; Manjanatha, Mugimane G; Miura, Daishiro; Uchikawa, Makoto; Mattison, Donald R; Morris, Suzanne M

2009-02-19

We have investigated the use of peripheral blood from the nonhuman primate (NHP) rhesus monkey (Macaca mulatta) as a model system for mutation detection. The rhesus monkey is metabolically closer to humans than most common laboratory animals, and therefore may be a relevant model for hazard identification and human risk assessment. To validate the model, conditions were determined for in vitro selection and expansion of 6-thioguanine-resistant (6-TGr) HPRT mutant and proaerolysin-resistant (ProAERr) PIG-A mutant lymphocytes from peripheral blood obtained by routine venipuncture. Also, flow cytometric methods were developed for the rapid detection of PIG-A mutant erythrocytes. The flow cytometric analysis of PIG-A mutant erythrocytes was based on enumerating cells deficient in surface markers attached to the cellular membrane via glycosylphosphatidyl inositol (GPI) anchors. Mutant cells were enumerated over an extended period of time in peripheral blood of male monkeys receiving daily doses of the electrolyte replenisher Prangtrade mark (a common carrier for oral delivery of drugs in NHPs), and in the blood of one male monkey treated with a single i.p. dose of 50mg/kg of N-ethyl-N-nitrosourea at approximately 2 years of age and another similar injection at approximately 3.5 years of age. The spontaneous PIG-A and HPRT T-cell mutant frequency (MF) was low in animals receiving Prang (0-8x10(-6)), and treatment with ENU resulted in a clearly detectable increase in the frequency of ProAERr and 6-TGr lymphocytes (up to approximately 28x10(-6) and approximately 30x10(-6), respectively). Also, the ENU-treated animal had higher frequency of GPI-deficient erythrocytes (46.5x10(-6) in the treated animal vs. 7.8+/-4.2x10(-6) in control animals). Our results indicate that the rhesus monkey can be a valuable model for the identification of agents that may impact upon human health as mutagens and that the PIG-A gene can be a useful target for detection of mutation in both white

Ordinal judgments of numerical symbols by macaques (Macaca mulatta)

NASA Technical Reports Server (NTRS)

Washburn, David A.; Rumbaugh, Duane M.

1991-01-01

Two rhesus monkeys (Macaca mulatta) learned that the arabic numerals 0 through 9 represented corresponding quantities of food pellets. By manipulating a joystick, the monkeys were able to make a selection of paired numerals presented on a computer screen. Although the monkeys received a corresponding number of pellets even if the lesser of the two numerals was selected, they learned generally to choose the numeral of greatest value even when pellet delivery was made arrhythmic. In subsequent tests, they chose the numerals of greater value when presented in novel combinations or in random arrays of up to five numerals. Thus, the monkeys made ordinal judgments of numerical symbols in accordance with their absolute or relative values.

Testicular Fibrous Hypoplasia in Cynomolgus Monkeys ( Macaca fascicularis): An Incidental, Congenital Lesion.

PubMed

Pereira Bacares, Marcia E; Vemireddi, Vimala; Creasy, Dianne

2017-06-01

Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.

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

PubMed

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.

Biosorption of copper(II) from aqueous solutions by green alga Cladophora fascicularis.

PubMed

Deng, Liping; Zhu, Xiaobin; Wang, Xinting; Su, Yingying; Su, Hua

2007-08-01

Biosorption is an effective means of removal of heavy metals from wastewater. In this work the biosorption behavior of Cladophora fascicularis was investigated as a function of pH, amount of biosorbent, initial Cu2+ concentration, temperature, and co-existing ions. Adsorption equilibria were well described by Langmuir isotherm models. The enthalpy change for the biosorption process was found to be 6.86 kJ mol(-1) by use of the Langmuir constant b. The biosorption process was found to be rapid in the first 30 min. The presence of co-existing cations such as Na+, K+, Mg2+, and Ca2+ and anions such as chloride, nitrate, sulfate, and acetate did not significantly affect uptake of Cu2+ whereas EDTA substantially affected adsorption of the metal. When experiments were performed with different desorbents the results indicated that EDTA was an efficient desorbent for the recovery of Cu2+ from biomass. IR spectral analysis suggested amido or hydroxy, C=O, and C-O could combine strongly with Cu2+.

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

NASA Astrophysics Data System (ADS)

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.

Tracing the phylogeographic history of Southeast Asian long-tailed macaques through mitogenomes of museum specimens.

PubMed

Yao, Lu; Li, Hongjie; Martin, Robert D; Moreau, Corrie S; Malhi, Ripan S

2017-11-01

The biogeographical history of Southeast Asia is complicated due to the continuous emergences and disappearances of land bridges throughout the Pleistocene. Here, we use long-tailed macaques (Macaca fascicularis), which are widely distributed throughout the mainland and islands of Southeast Asia, asa model for better understanding the biogeographical patterns of diversification in this geographically complex region. A reliable intraspecific phylogeny including individuals from localities on oceanic islands, continental islands, and the mainland is needed to trace relatedness along with the pattern and timing of colonization in this region. We used high-throughput sequencing techniques to sequence mitochondrial genomes (mitogenomes) from 95 Southeast Asian M. fascicularis specimens housed at natural history museums around the world. To achieve a comprehensive picture, we more than tripled the mitogenome sample size for M. fascicularis from previous studies, and for the first time included documented samples from the Philippines and several small Indonesian islands. Confirming the result from a previous, recent intraspecific phylogeny for M. fascicularis, the newly reconstructed phylogeny of 135 specimens divides the samples into two major clades: Clade A includes haplotypes from the mainland and some from northern Sumatra, while Clade B includes all insular haplotypes along with lineages from southern Sumatra. This study resolves a previous disparity by revealing a disjunction in the origin of Sumatran macaques, with separate lineages originating within the two major clades, suggesting that at least two major migrations to Sumatra occurred. However, our dated phylogeny reveals that the two major clades split ∼1.88Ma, which is earlier than in previously published phylogenies. Our new data reveal that most Philippine macaque lineages diverged from the Borneo stock within the last ∼0.06-0.43Ma. Finally, our study provides insight into successful sequencing of DNA

Effects of ethanol on cocaine self-administration in monkeys responding under a second-order schedule of reinforcement.

PubMed

John, William S; Nader, Michael A

2017-01-01

Concurrent alcohol use among cocaine abusers is common but the behavioral variables that promote co-abuse are not well understood. The present study examined the effects of intragastric (i.g.) ethanol (EtOH) administration in monkeys responding under a schedule of cocaine reinforcement in which extensive drug seeking was maintained by conditioned stimuli. Four adult male cynomolgus monkeys (Macaca fascicularis) were trained to respond under a second-order fixed-interval (FI) 600s (fixed-ratio (FR) 30:S) schedule of cocaine (0.003-0.56mg/kg/injection) presentation. Sessions ended after 5 injections or 90min had elapsed. Different EtOH doses (0.5-2.0g/kg, i.g.) were administered 30min before the session, typically on Tuesdays and Fridays. Blood ethanol concentrations (BECs) were also assessed. Pattern of FI responding was assessed by determining quarter-life (QL) values. Cocaine self-administration was characterized as an inverted U-shaped function of dose; QL values increased monotonically with dose. EtOH pretreatments dose-dependently decreased self-administration at several cocaine doses in 3 of 4 monkeys. In one animal, EtOH increased low-dose cocaine-maintained responding. For all monkeys, QL values were increased by EtOH when low- and high-cocaine doses were self-administered, suggesting additive effects of EtOH and cocaine. Furthermore, BECs were not altered following cocaine self-administration. The reductions in cocaine self-administration and the increases in QL values following EtOH, suggest that EtOH was enhancing cocaine-related conditioned reinforcement. A better understanding of the behavioral mechanisms that mediate the co-abuse of alcohol and cocaine will lead to improved treatments for both drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pre- and Post-harvest Influences on Seed Dormancy Status of an Australian Goodeniaceae species, Goodenia fascicularis

PubMed Central

Hoyle, Gemma L.; Steadman, Kathryn J.; Daws, Matthew I.; Adkins, Steve W.

2008-01-01

Background and Aims The period during which seeds develop on the parent plant has been found to affect many seed characteristics, including dormancy, through interactions with the environment. Goodenia fascicularis (Goodeniaceae) seeds were used to investigate whether seeds of an Australian native forb, harvested from different environments and produced at different stages of the reproductive period, differ in dormancy status. Methods During the reproductive phase, plants were grown ex situ in warm (39/21 °C) or cool (26/13 °C) conditions, with adequate or limited water availability. The physiological dormancy of resulting seeds was measured in terms of the germination response to warm stratification (34/20 °C, 100 % RH, darkness). Key Results Plants in the cool environment were tall and had high above-ground biomass, yet yielded fewer seeds over a shorter, later harvest period when compared with plants in the warm environment. Seeds from the cool environment also had higher viability and greater mass, despite a significant proportion (7 % from the cool-wet environment) containing no obvious embryo. In the warm environment, the reproductive phase was accelerated and plants produced more seeds despite being shorter and having lower above-ground biomass than those in the cool environment. Ten weeks of warm stratification alleviated physiological dormancy in seeds from all treatments resulting in 80–100 % germination. Seeds that developed at warm temperatures were less dormant (i.e. germination percentages were higher) than seeds from the cool environment. Water availability had less effect on plant and seed traits than air temperature, although plants with reduced soil moisture were shorter, had lower biomass and produced fewer, less dormant seeds than plants watered regularly. Conclusions Goodenia fascicularis seeds are likely to exhibit physiological dormancy regardless of the maternal environment. However, seeds collected from warm, dry environments are

Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes

PubMed Central

Curnow, E. C.; Ryan, J. P.; Saunders, D. M.; Hayes, E. S.

2010-01-01

Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes. PMID:20591337

Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes.

PubMed

Curnow, E C; Ryan, J P; Saunders, D M; Hayes, E S

2010-01-01

Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes.

Annual variations in sexual hormones and births' frequency in female stump-tailed macaques (Macaca arctoides).

PubMed

Mondragón-Ceballos, R; García-Granados, M D; Matamoros-Trejo, G; Hernández-López, L E

2018-03-01

Although the breeding seasonality in Macaca arctoides have been studied over a long period of time, it is still controversial whether reproduction in this primate tend to increase during certain months of the year as it happens in most of the macaque species. Many authors have classified Macaca arctoides as not being seasonal species. Nonetheless, there were no reports, about seasonal variations of female sexual hormones to demonstrate that asseveration. Therefore, in the present study we collect 1611 fecal samples from June 2009 to November 2010 from 10 female stump-tailed macaques to measure 17β-estradiol and progesterone concentrations. Also, we included the birth frequency per year, in order to identify if sexual hormones peaked at a certain period of the year, thus, births would be occurring six months later according to the gestation length of stump-tailed macaques. Our results indicate two mating seasons per year in stump-tailed macaques: one in July-August and a second one in November. The distribution of the birth frequency, throughout the year support these results. We conclude that stump-tail macaques have a discrete seasonality no different than most of macaques' species. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of the vaginal environment of Macaca mulatta and Macaca nemestrina throughout the menstrual cycle

PubMed Central

Hadzic, Sarah V.; Wang, Xiaolei; Dufour, Jason; Doyle, Lara; Marx, Preston A.; Lackner, Andrew A.; Paulsen, Daniel B.; Veazey, Ronald S.

2014-01-01

Problem Pigtail macaques, Macaca nemestrina (PT) are more susceptible to vaginal transmission of simian immunodeficiency virus (SIV) and other sexually transmitted diseases (STD) than rhesus macaques (RM). However, comparative studies to explore the reasons for these differences are lacking. Method of Study Here we compared differences in hormone levels and vaginal mucosal anatomy and thickness of RM and PT through different stages of the menstrual cycle. Concentrations of plasma estradiol (E2) and progesterone (P4) were determined weekly, and vaginal biopsies examined at day 0 and 14 of the menstrual cycle. Results Consistent changes in vaginal epithelial thickness occurred at different stages of the menstrual cycle. In both species, the vaginal epithelium was significantly thicker in the follicular than in luteal phase. Keratinized epithelium was strikingly much more prominent in RM, especially during the luteal phase. Further, the vaginal epithelium was significantly thinner and the P4:E2 ratio was higher in PT during luteal phase than RM. Conclusions Striking anatomical differences in the vaginal epithelium between rhesus and pigtail macaques combined with differences in P4:E2 ratio support the hypothesis that thinning and less keratinization of the vaginal epithelium may be involved in the greater susceptibility of pigtail macaques to vaginal transmission of SIV or other STD. PMID:24521395

Different Neural Strategies for Multimodal Integration: Comparison of two Macaque Monkey Species

PubMed Central

Sadeghi, Soroush G.; Mitchell, Diana E.; Cullen, Kathleen E.

2012-01-01

The integration of neck proprioceptive and vestibular inputs underlies the generation of accurate postural and motor control. Recent studies have shown that central mechanisms underlying the integration of these sensory inputs differ across species. Notably, in rhesus monkey (macaca mulata), an Old World monkey, neurons in the vestibular nuclei are insensitive to passive stimulation of neck proprioceptors. In contrast, in squirrel monkey, a New World monkey, stimulation produces robust modulation. This has led to the suggestion that there are differences in how sensory information is integrated during self motion in old versus New World monkeys. To test this hypothesis, we recorded from neurons in the vestibular nuclei of another species in the macaca genus (i.e., macaca fascicularis (cynomolgus monkey)). Recordings were made from vestibular-only (VO) and position-vestibular-pause (PVP) neurons. The majority (53%) of neurons in both groups were sensitive to neck proprioceptive and vestibular stimulation during passive body-under-head and whole body rotation, respectively. Furthermore, responses during passive rotations of the head-on-body were well predicted by the linear summation of vestibular and neck responses (which were typically antagonistic). During active head movement, the responses of VO and PVP neurons were further attenuated (relative to a model based on linear summation) for the duration of the active head movement or gaze shift, respectively. Taken together, our findings show that the brain's strategy for the central processing of sensory information can vary even within a single genus. We suggest that similar divergence may be observed in other areas in which multimodal integration occurs. PMID:19283371

Pharmacokinetics of a Novel, Transdermal Fentanyl Solution in Rhesus Macaques (Macaca mulatta)

PubMed Central

Salyards, Gregory W; Lemoy, Marie-Josee; Knych, Heather K; Hill, Ashley E; Christe, Kari L

2017-01-01

Rhesus macaques (Macaca mulatta) are the most commonly used NHP biomedical model and experience both research and clinical procedures requiring analgesia. Opioids are a mainstay of analgesic therapy. A novel, transdermal fentanyl solution (TFS) has been developed as a long-acting, single-administration topical opioid and was reported to provide at least 4 d of effective plasma concentrations in beagles (Canis familiaris). To evaluate the pharmacokinetic profile of TFS in healthy adult rhesus macaques, we used a 2-period, 2-treatment crossover study of a single topical administration of 1.3 (25) and 2.6 mg/kg (50 μL/kg) TFS. TFS was applied to the clipped dorsal skin of adult rhesus macaques (n = 6; 3 male, 3 female) under ketamine sedation (10 mg/kg IM). We hypothesized that TFS in rhesus macaques would provide at least 4 d of effective plasma concentrations (assumed to be ≥ 0.2 ng/mL, based on human studies). Plasma fentanyl concentrations were determined by liquid chromatography–tandem mass spectrometry before drug administration and at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 240, 336, 408, and 504 h afterward. Noncompartmental pharmacokinetic analysis was performed. For each dose (1.3 and 2.6 mg/kg), respectively, the maximal plasma concentration was 1.95 ± 0.40 and 4.19 ± 0.69 ng/mL, occurring at 21.3 ± 4.1 and 30.7 ± 8.7 h; the AUC was 227.3 ± 31.7 and 447.0 ± 49.1 h/ng/mL, and the terminal elimination half-life was 93.7 ± 7.1 and 98.8 ± 5.4 h. No adverse effects were noted after drug administration at either dose. Macaques maintained plasma fentanyl concentrations of 0.2 ng/mL or greater for at least 7 d after 1.3 mg/kg and at least 10 d after 2.6 mg/kg topical administration of TFS. A single TFS dose may provide efficacious analgesia to rhesus macaques and reduce stress, discomfort, and risk to animals and personnel. PMID:28724494

THE EFFECT OF IONIZING RADIATION ON ACETYLCHOLINE METABOLISM IN MACACA- RHESUS MONKEYS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demin, N.N.; Korneeva, N.V.; Shaternikov, V.A.

1961-11-01

In macaca-rhesus monkeys the normal content of free acetylcholine in the mucosa of the small intestine was higher, as it was in brain and liver, than bound acetyl choline. The total cholinesterase activity and, particularly, the activity of acetylcholinesterase and non-specific cholinesterase in control monkeys is highest in brain, followed by intestinal mucosa and liver. One to three days after gamma -irradiation of the monkey at a dose of 600 r the amount of free and bound acetylcholine in the mucosa of the small intestine increased, while it decreased in liver. The total cholinesterase activity in the mucosa of themore » small intestine during this period increased, in general because of the increase in the activity of non-specific cholinesterase. In the liver the increase in total cholinesterase activity also occurred because of an increase in non-specific cholinesterase activity, but was less clear-cut and occurred later (the third day after irradiation). In animals irradiated 2 to 3 years before the investigation, an increased concentration of free acetylcholine in brain, liver, and mucosa of the small intestine was noted; but there were no ehanges in bound acetylcholine. The total cholinesterase activity increased in liver as a result of acetyl cholinesterase increase and non-specific enzymes, and in mucosa of the small intestine only as a result of acetylcholinesterase activity. In brain the total cholinesterase activity decreased as a consequence of a decrease in acetylcholinesterase activity. (auth)« less

Molecular phylogeny of the hominoid primates as indicated by two-dimensional protein electrophoresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldman, D.; Giri, P.R.; O'Brien, J.O.

1987-05-01

A molecular phylogeny for the hominoid primates was constructed by using genetic distances from a survey of 383 radiolabeled fibroblast polypeptides resolved by two-dimensional electrophoresis (2DE). An internally consistent matrix of Nei genetic distances was generated on the basis of variants in electrophoretic position. The derived phylogenetic tree indicated a branching sequence, from oldest to most recent, of cercopithecoids (Macaca fascicularis), gibbon-siamang, orangutan, gorilla, and human-chimpanzee. A cladistic analysis of 240 electrophoretic characters that varied between ape species produced an identical tree. Genetic distance measures obtained by 2DE are largely consistent with those generated by other molecular procedures. In addition,more » the 2DE data set appears to resolve the human-chimpanzee-gorilla trichotomy in favor of a more recent association of chimpanzees and humans.« less

Characterization of a prototype strain of hepatitis E virus.

PubMed

Tsarev, S A; Emerson, S U; Reyes, G R; Tsareva, T S; Legters, L J; Malik, I A; Iqbal, M; Purcell, R H

1992-01-15

A strain of hepatitis E virus (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, was characterized extensively. Six cynomolgus monkeys (Macaca fascicularis) were infected with a strain of hepatitis E virus from Pakistan. Reverse transcription-polymerase chain reaction was used to determine the pattern of virus shedding in feces, bile, and serum relative to hepatitis and induction of specific antibodies. Virtually the entire genome of SAR-55 (7195 nucleotides) was sequenced. Comparison of the sequence of SAR-55 with that of a Burmese strain revealed a high level of homology except for one region encoding 100 amino acids of a putative nonstructural polyprotein. Identification of this region as hypervariable was obtained by partial sequencing of a third isolate of hepatitis E virus from Kirgizia.

Predation on pupa of Chrysomya rufifacies (Marquart) (Diptera: Calliphoridae) by parasitoid, Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae) and Ophyra spinigera larva (Diptera: Muscidae).

PubMed

Chin, Heo Chong; Ahmad, Nazni Wasi; Lim, Lee Han; Jeffery, John; Omar, Baharudin; Dhang, Chen Chee; Weng, Lau Koon; Sofian-Azirun, Mohd

2009-12-01

A forensic entomological study was conducted using monkey carcasses (Macaca fascicularis Raffles) that were placed in either an outdoor or indoor environment at a coastal area in Tanjung Sepat, Selangor, Malaysia during May until August 2008. We collected pupae of Chrysomya rufifacies (Marquart) from the carcasses and kept them individually. The emergence of 13 parasitic microhymenopteran, from one of the pupae occurring within a week were identified as Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae). Another observation was made whereby a pupa of C. rufifacies was predated by a muscid larva, Ophyra spinigera (Stein). The larva squeezed into the pupa and consumed the contents. This paper report C. rufifacies as a new host record for E. philippinensis in Malaysia and highlighted the predatory behavior of O. spinigera larva in natural environment.

Primate-to-Human Retroviral Transmission in Asia

PubMed Central

Engel, Gregory A.; Schillaci, Michael A.; Rompis, Aida; Putra, Artha; Suaryana, Komang Gde; Fuentes, Agustin; Beer, Brigitte; Hicks, Sarah; White, Robert; Wilson, Brenda; Allan, Jonathan S.

2005-01-01

We describe the first reported transmission to a human of simian foamy virus (SFV) from a free-ranging population of nonhuman primates in Asia. The transmission of an exogenous retrovirus, SFV, from macaques (Macaca fascicularis) to a human at a monkey temple in Bali, Indonesia, was investigated with molecular and serologic techniques. Antibodies to SFV were detected by Western blotting of serum from 1 of 82 humans tested. SFV DNA was detected by nested polymerase chain reaction (PCR) from the blood of the same person. Cloning and sequencing of PCR products confirmed the virus's close phylogenetic relationship to SFV isolated from macaques at the same temple. This study raises concerns that persons who work at or live around monkey temples are at risk for infection with SFV. PMID:16022776

Reemergence of Reston ebolavirus in Cynomolgus Monkeys, the Philippines, 2015.

PubMed

Demetria, Catalino; Smith, Ina; Tan, Titus; Villarico, Daniel; Simon, Edson Michael; Centeno, Rex; Tachedjian, Mary; Taniguchi, Satoshi; Shimojima, Masayuki; Miranda, Noel Lee J; Miranda, Mary Elizabeth; Rondina, Melissa Marie R; Capistrano, Rowena; Tandoc, Amado; Marsh, Glenn; Eagles, Debbie; Cruz, Ramses; Fukushi, Shuetsu

2018-07-01

In August 2015, a nonhuman primate facility south of Manila, the Philippines, noted unusual deaths of 6 cynomolgus monkeys (Macaca fascicularis), characterized by generalized rashes, inappetence, or sudden death. We identified Reston ebolavirus (RESTV) infection in monkeys by using serologic and molecular assays. We isolated viruses in tissues from infected monkeys and determined viral genome sequences. RESTV found in the 2015 outbreak is genetically closer to 1 of the 4 RESTVs that caused the 2008 outbreak among swine. Eight macaques, including 2 also infected with RESTV, tested positive for measles. Concurrently, the measles virus was circulating throughout the Philippines, indicating that the infection of the macaques may be a reverse zoonosis. Improved biosecurity measures will minimize the public health risk, as well as limit the introduction of disease and vectors.

Retinoid metabolism and transplacental pharmacokinetics in the cynomolgus monkey following a nonteratogenic dosing regimen with all-trans-retinoic acid.

PubMed

Tzimas, G; Nau, H; Hendrickx, A G; Peterson, P E; Hummler, H

1996-11-01

Retinoids often exhibit a complex metabolic pattern and differential transplacental kinetics, which make it difficult to pinpoint the proximate compound responsible for the observed teratogenic effect. We have therefore studied the pharmacokinetics and metabolism of all-trans-retinoic acid (all-trans-RA) in cynomolgus monkeys following application of a nonteratogenic dosing regimen and compared the results with corresponding data from a previous study with a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193]. All-trans-RA was administered to pregnant cynomolgus monkeys (Macaca fascicularis) by nasogastric intubation at a dose of 5 mg/kg body wt once daily from gestational day (GD) 16 to 26 and twice daily at 8-h intervals from GD 27 to 31. Examination of the fetuses of four dams on GD 100 +/- 2 showed no embryotoxic or teratogenic effects of the applied dosing regimen (Experiment 1). Maternal plasma retinoid pharmacokinetics on GD 16, 26, and 31 as well as embryonic retinoid profiles after the last drug administration on GD 31 were determined in thirteen further dams (Experiment 2). All-trans-RA reached much lower plasma concentrations after the last two treatments on GD 31 than after the first one on GD 16 and the eleventh one on GD 26 (0-24-h area-under-the-concentration-time-curve (AUC) values: 104 +/- 59 ng x h/ml (after the last treatment on GD 31), 189 +/- 110 (GD 16) and 393 +/- 305 ng x h/ml (GD 26). The predominant plasma metabolites of all-trans-RA were its beta-glucuronide and the beta-glucuronide of all-trans-4-oxo-RA. Both of these retinoids accumulated in the plasma during the period of treatment and displayed AUC values 5- to 30-fold higher than those of all-trans-RA. Embryonic concentrations of all-trans-RA were not increased over endogenous levels after the last administration on GD 31 when plasma concentrations were low. To evaluate the placental transport of all-trans-RA in the presence of high plasma

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

PubMed Central

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

Comparison of the vaginal environment of Macaca mulatta and Macaca nemestrina throughout the menstrual cycle.

PubMed

Hadzic, Sarah V; Wang, Xiaolei; Dufour, Jason; Doyle, Lara; Marx, Preston A; Lackner, Andrew A; Paulsen, Daniel B; Veazey, Ronald S

2014-04-01

Pigtail macaques, Macaca nemestrina (PT), are more susceptible to vaginal transmission of simian immunodeficiency virus (SIV) and other sexually transmitted diseases (STD) than rhesus macaques (RM). However, comparative studies to explore the reasons for these differences are lacking. Here, we compared differences in hormone levels and vaginal mucosal anatomy and thickness of RM and PT through different stages of the menstrual cycle. Concentrations of plasma estradiol (E2) and progesterone (P4) were determined weekly, and vaginal biopsies examined at days 0 and 14 of the menstrual cycle. Consistent changes in vaginal epithelial thickness occurred at different stages of the menstrual cycle. In both species, the vaginal epithelium was significantly thicker in the follicular than in luteal phase. Keratinized epithelium was strikingly much more prominent in RM, especially during the luteal phase. Further, the vaginal epithelium was significantly thinner, and the P4:E2 ratio was higher in PT during luteal phase than RM. Striking anatomic differences in the vaginal epithelium between rhesus and pigtail macaques combined with differences in P4:E2 ratio support the hypothesis that thinning and less keratinization of the vaginal epithelium may be involved in the greater susceptibility of pigtail macaques to vaginal transmission of SIV or other STD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Age-Associated Pathology in Rhesus Macaques (Macaca mulatta)

PubMed Central

Simmons, H. A.

2018-01-01

The rhesus macaque (Macaca mulatta) is one of the most extensively used nonhuman primate models for human diseases. This article presents a literature review focusing on major organ systems and age-associated conditions in humans and primates, combined with information from the Wisconsin National Primate Research Center Electronic Health Record database to highlight and contrast age-associated lesions in geriatric rhesus macaques with younger cohorts. Rhesus macaques are excellent models for age-associated conditions, including diabetes, osteoarthritis, endometriosis, visual accommodation, hypertension, osteoporosis, and amyloidosis. Adenocarcinoma of the large intestine (ileocecocolic junction, cecum, and colon) is the most common spontaneous neoplasm in the rhesus macaque. A combination of cross-sectional and longitudinal studies is required to truly define mechanisms of maturation, aging, and the pathology of age-associated conditions in macaques and thus humans. The rhesus macaque is and will continue to be an appropriate and valuable model for investigation of the mechanisms and treatment of age-associated diseases. PMID:26864889

Exploring of Primate Models of Tick-Borne Flaviviruses Infection for Evaluation of Vaccines and Drugs Efficacy

PubMed Central

Pripuzova, Natalia S.; Gmyl, Larissa V.; Romanova, Lidiya Iu.; Tereshkina, Natalia V.; Rogova, Yulia V.; Terekhina, Liubov L.; Kozlovskaya, Liubov I.; Vorovitch, Mikhail F.; Grishina, Karina G.; Timofeev, Andrey V.; Karganova, Galina G.

2013-01-01

Tick-borne encephalitis virus (TBEV) is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV) in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8–16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to TBEV than C

Thymus development in Macaca fascicularis (Cynomolgus monkey): an approach for toxicology and embryology.

PubMed

Buse, Eberhard; Habermann, Gunnar; Vogel, Friedhelm

2006-05-01

Thymus development was studied in the cynomolgus monkey from day 35 of gestation (gd 35) to the stage of advanced involution in a 21-year-old monkey. Special emphasis was placed on thymus cell generation and cellular pattern formation. At gd 35, the epithelial bud of the thymus was visible in a sagittal position at the level of the thoracic aperture. At gd 50, first lymphocyte-like cells and few Human Leukocyte Antigen-D Region (HLA-DR) immunoreactive cells appeared. The cortico-medullary differentiation, Hassall's body precursors and faint immunoreactivity for T-lymphocytes (CD 3-positive) were detected from gd 60 onwards. First macrophages (CD 68 positive) were apparent at day 70, first CD 20 immunoreactive cells (B-lymphocyte-like cells) at gd 85, and natural killer cells (M1014 immunoreactive) at gd 100. At gd 100 all evaluated cell populations present in the adult cynomolgus monkey thymus were in place, whereas no B- and T-cell precursors or (CD 34 and CD 117, respectively) dendritic cells (CD 35 positive cells) were present. All these immunopositive cells persisted, partly with changing distribution patterns, until the advanced age of 21 years with the exception of natural killer cells, which were present only until adult ages (evaluation at 4-7 years). The rationale of this study was to analyse thymic development in the cynomolgus monkey and to evaluate the relevance of the development of thymus in non-human primate as a model for corresponding human targeted toxicological research.

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

PubMed

Mohedano-Moriano, Alicia; Muñoz-López, Mónica; Sanz-Arigita, Ernesto; Pró-Sistiaga, Palma; Martínez-Marcos, Alino; Legidos-Garcia, María Ester; Insausti, Ana María; Cebada-Sánchez, Sandra; Arroyo-Jiménez, María Del Mar; Marcos, Pilar; Artacho-Pérula, Emilio; Insausti, Ricardo

2015-12-01

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. © 2015 Wiley Periodicals, Inc.

Comparative proteomic analyses of macular and peripheral retina of cynomolgus monkeys (Macaca fascicularis).

PubMed

Okamoto, Haru; Umeda, Shinsuke; Nozawa, Takehiro; Suzuki, Michihiro T; Yoshikawa, Yasuhiro; Matsuura, Etsuko T; Iwata, Takeshi

2010-01-01

The central region of the primate retina is called the macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create a neural network adapted for high visual acuity. Damage to the fovea, e.g., by macular dystrophies and age-related macular degeneration, can reduce central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in the macula which differ from those in the peripheral retina in expression level. To investigate whether the distribution of proteins in the macula is different from the peripheral retina, proteomic analyses of tissues from these two regions of cynomolgus monkeys were compared. Two-dimensional gel electrophoresis and mass spectrometry identified 26 proteins that were present only in the macular gel spots. The expression levels of five proteins, cone photoreceptor specific arrestin-C, gamma-synuclein, epidermal fatty acid binding protein, tropomyosin 1alpha chain, and heterogeneous nuclear ribonucleoproteins A2/B1, were significantly higher in the macula than in the peripheral retina. Immunostaining of macula sections by antibodies to each identified protein revealed unique localization in the retina, retinal pigment epithelial cells and the choroidal layer. Some of these proteins were located in cells with higher densities in the macula. We suggest that it will be important to study these proteins to determine their contribution to the pathogenesis and progression of macula diseases.

Spontaneous Findings in the Eyes of Cynomolgus Monkeys ( Macaca fascicularis) of Mauritian Origin.

PubMed

Woicke, Jochen; Haile, Solomon; Mysore, Jagannatha; Peden, W Michael; Lejeune, Typhaine; Sanderson, Thomas; Brodie, Thomas

2018-04-01

Spontaneous findings noted in the eyes of Mauritian cynomolgus monkeys are described and descriptions are supplemented with illustrations. Findings observed after extensive histopathologic examinations (20 to 44 sections per eye) from 20 control, 17 treatment-naive stock monkeys, and 2 findings noted in drug-treated monkeys that were considered to be spontaneous are included. Also included are findings from 361 control monkeys of routine toxicity studies performed at our laboratories, for most of which a standard histopathological examination of 1 section per eye was conducted. Common observations in monkeys examined extensively and in historical controls were limited to lymphocytic or mononuclear cell infiltrations of the uvea and/or conjunctiva/sclera and, less commonly observed, melanocytoma of the ciliary body or iris. Findings noted only in monkeys examined extensively consisted of inflammation of the conjunctiva, ora serrata cysts, glial nodules, focal degeneration of the retina, cystoid degeneration of the central retina, ballooning degeneration of the ciliary epithelium, cyst of the ciliary body, and decreased pigmentation of the retinal pigment epithelium. Changes recorded only in historical controls included retinal atrophy and nuclear displacement in the retina. Lesions are discussed and compared with pertinent literature.

Histopathology of Incidental Findings in Cynomolgus Monkeys (Macaca Fascicularis) Used in Toxicity Studies

PubMed Central

Sato, Junko; Doi, Takuya; Kanno, Takeshi; Wako, Yumi; Tsuchitani, Minoru; Narama, Isao

2012-01-01

The purpose of our publication is to widely communicate pictures of spontaneous findings occurring in cynomolgus monkeys. Focal lymphoplasmacytic infiltration is commonly seen in the general organs. The frequency and severity of these lesions may be influenced by the administration of drugs with an effect on the immune system. Lymphoplasmacytic infiltration in the lamina propria of the stomach is also frequently seen in cynomolgus monkeys, and it is caused mainly by a Helicobacter pylori infection. Various degrees of brown pigments are observed in various organs, and it is possible to distinguish the material of the pigments by its morphological features and site. A focal/segmental glomerular lesion is occasionally seen in a section of the kidney, and the minimal lesion has no influence on the urinalysis. We showed the common glomerular lesions in HE-stained sections, as well as in PAM- or PAS-stained sections, for understanding the details. Young and pubertal monkeys are usually used in toxicity studies; therefore, understanding various maturation stages of the genital system is important. In particular, the female genital system needs to be understood in the morphology, because their cyclic changes are different from other laboratory animals. Thus, we present the normal features of the cyclic changes of the female genital organs. Furthermore, we provide more information on spontaneous findings in cynomolgus monkeys for exact diagnoses in toxicity studies. PMID:22481861

Postnatal change in sulcal length asymmetry in cerebrum of cynomolgus monkeys (Macaca fascicularis).

PubMed

Sakamoto, Kazuhito; Sawada, Kazuhiko; Fukunishi, Katsuhiro; Noritaka, Imai; Sakata-Haga, Hiromi; Yoshihiro, Fukui

2014-02-01

The purpose of this study was to determine the timing of the onset of adult-type sulcal length asymmetry during postnatal development of the male cynomolgus monkey cerebrum. The monkey brain has already reached adult size by 3 months of age, although the body weight only represents 1/8 of the adult body weight by that time. The fronto-occipital length and the cerebral width also reached adult levels by that postnatal age with no left/right bias. Consistently, lengths of the major primary sulci reached adult levels by 3 months of age, and then decreased slightly in sexually mature monkeys (4-6.5 years of age). Asymmetry quotient analysis showed that sulcal length asymmetry patterns gradually changed during postnatal development. The male adult pattern of sulcal length asymmetry was acquired after 24 months of age. In particular, age-dependent rightward lateralization of the arcuate sulcal length was revealed during cerebral maturation by three-way ANOVA. The results suggest that the regional difference in cerebral maturation from adolescence to young adulthood modifies the sulcal morphology with characteristic asymmetric patterns in male cynomolgus monkeys. Copyright © 2013 Wiley Periodicals, Inc.

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

PubMed

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

2014-04-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative anatomy of the arm muscles of the Japanese monkey (Macaca fuscata) with some comments on locomotor mechanics and behavior.

PubMed

Aversi-Ferreira, Tales Alexandre; Aversi-Ferreira, Roqueline A G M F; Bretas, Rafael Vieira; Nishimaru, Hiroshi; Nishijo, Hisao

2016-08-01

The anatomical literature on the genus Macaca has focused mainly on the rhesus monkey. However, some aspects in the positional behaviors of the Japanese monkey may be different from those in rhesus monkey, suggesting that the anatomical details of these species are divergent. Four thoracic limbs of Macaca fuscata adults were dissected. The arm muscles in Japanese macaques are more similar to rhesus monkeys and Papio; these characteristics are closer to those of bearded capuchins than apes, indicating more proximity of this genus to New World primates. The anatomical features observed favor quadrupedal locomotor behaviors on the ground and in arboreal environments. Japanese monkeys, rhesus monkeys, and bearded capuchins, which share more primitive characteristics in their arm muscles, present features that favor both arboreal and quadrupedal locomotor behaviors, whereas apes, mainly Pan and Gorilla, which spend more time on the ground, present more quadrupedal specializations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Meningoencephalitis Due to Listeria monocytogenes in a Pregnant Rhesus Macaque (Macaca mulatta)

PubMed Central

Lemoy, Marie-Josee MF; Lopes, Danielle A; Reader, J Rachel; Westworth, Diccon R; Tarara, Ross P

2012-01-01

We here report a spontaneous case of meningoencephalitis due to Listeria monocytogenes in an adult primiparous rhesus macaque (Macaca mulatta) during an outbreak of listeriosis in an outdoor enclosure. Clinical signs included tremors, abnormal posture, and altered mental status. Hematology and analyses of cerebrospinal fluid were consistent with bacterial infection. Pure cultures of L. monocytogenes were recovered from the placenta–abortus, cerebrospinal fluid, and brain tissue. The macaque did not respond to treatment and was euthanized. Histopathologic examination of the brain revealed acute meningoencephalitis. This case represents an unusual clinical and pathologic presentation of listeriosis in a nonhuman primate in which the dam and fetus both were affected. PMID:23114049

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

PubMed

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

2009-01-01

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

Effect of chronic administration of Tamoxifen on fertility in male bonnet monkeys (Macaca radiata).

PubMed

Rao, A J; Ramachandra, S G; Ramesh, V; Krishnamurthy, H N; Jayaraman, S; Gopalakrishnan, K; Juneja, H S

1998-01-01

Administration of Tamoxifen via the Alzet pump at a rate of 50 micrograms hr-1 for 90 days in the adult male bonnet monkeys Macaca radiata had no effect on the serum testosterone concentration determined at 10 AM and 10 PM as well as total sperm count determined at 15-day intervals over a period of 260 days. However, a significant reduction in sperm motility was observed beyond 90 days up until the 225th day. Breeding studies conducted from day 90 to 260 revealed that these males were infertile.

Characterization of a prototype strain of hepatitis E virus.

PubMed Central

Tsarev, S A; Emerson, S U; Reyes, G R; Tsareva, T S; Legters, L J; Malik, I A; Iqbal, M; Purcell, R H

1992-01-01

A strain of hepatitis E virus (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, was characterized extensively. Six cynomolgus monkeys (Macaca fascicularis) were infected with a strain of hepatitis E virus from Pakistan. Reverse transcription-polymerase chain reaction was used to determine the pattern of virus shedding in feces, bile, and serum relative to hepatitis and induction of specific antibodies. Virtually the entire genome of SAR-55 (7195 nucleotides) was sequenced. Comparison of the sequence of SAR-55 with that of a Burmese strain revealed a high level of homology except for one region encoding 100 amino acids of a putative nonstructural polyprotein. Identification of this region as hypervariable was obtained by partial sequencing of a third isolate of hepatitis E virus from Kirgizia. Images PMID:1731327

Intra-oral colonization of macaque monkeys by Actinobacillus actinomycetemcomitans

PubMed Central

Beighton, David; Taichman, Norton S.; Simpson, David L.; Dirienzo, Joseph M.; Johnson, Newell W.

2012-01-01

Actinobacillus actinomycetemcomitans was acquired by captive Macaca fascicularis 3 to 6 months after birth, and all monkeys aged over 6 months harbored detectable levels. This microorganism was most frequently isolated from the gingival plaque of the incisor (and other) teeth compared with other oral sites. Strains were leukotoxic by bioassay and Western blot analysis. Antibodies in macaque serum contained neutralized the leukotoxin of a human A. actinomycetemcomitans strain. High titres of maternal neutralizing anti-leukotoxin antibodies were detected in neonates; the titre then fell rapidly so that by 6 months the antibody titer was zero. Antileukotoxin antibody production was detected after 6 months of age, rapidly reaching a high level within 2 years after birth. The presence of leukotoxic strains of A. actinomycetemcomitans in the gingival region did not appear to be correlated with an increase in susceptibility to periodontal disease. PMID:2628866

Tamoxifen-DNA adduct formation in monkey and human reproductive organs.

PubMed

Hernandez-Ramon, Elena E; Sandoval, Nicole A; John, Kaarthik; Cline, J Mark; Wood, Charles E; Woodward, Ruth A; Poirier, Miriam C

2014-05-01

The estrogen analog tamoxifen (TAM), used for adjuvant therapy of breast cancer, induces endometrial and uterine tumors in breast cancer patients. Proliferation stimulus of the uterine endometrium is likely involved in tumor induction, but genotoxicity may also play a role. Formation of TAM-DNA adducts in human tissues has been reported but remains controversial. To address this issue, we examined TAM-DNA adducts in uteri from two species of monkeys, Erythrocebus patas (patas) and Macaca fascicularis (macaque), and in human endometrium and myometrium. Monkeys were given 3-4 months of chronic TAM dosing scaled to be equivalent to the daily human dose. In the uteri, livers and brains from the patas (n = 3), and endometrium from the macaques (n = 4), TAM-DNA adducts were measurable by TAM-DNA chemiluminescence immunoassay. Average TAM-DNA adduct values for the patas uteri (23 adducts/10(8) nucleotides) were similar to those found in endometrium of the macaques (19 adducts/10(8) nucleotides). Endometrium of macaques exposed to both TAM and low-dose estradiol (n = 5) averaged 34 adducts/10(8) nucleotides. To examine TAM-DNA persistence in the patas, females (n = 3) were exposed to TAM for 3 months and to no drug for an additional month, resulting in low or non-detectable TAM-DNA in livers and uteri. Human endometrial and myometrial samples from women receiving (n = 8) and not receiving (n = 8) TAM therapy were also evaluated. Women receiving TAM therapy averaged 10.3 TAM-DNA adducts/10(8) nucleotides, whereas unexposed women showed no detectable TAM-DNA. The data indicate that genotoxicity, in addition to estrogen agonist effects, may contribute to TAM-induced human endometrial cancer.

Rhesus monkeys (Macaca mulatta) map number onto space

PubMed Central

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, 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. PMID:24762923

Rhesus monkeys (Macaca mulatta) map number onto space.

PubMed

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. Copyright © 2014 Elsevier B.V. All rights reserved.

Standardized Full-Field Electroretinography in the Green Monkey (Chlorocebus sabaeus)

PubMed Central

Bouskila, Joseph; Javadi, Pasha; Palmour, Roberta M.; Bouchard, Jean-François; Ptito, Maurice

2014-01-01

Abstract Full-field electroretinography is an objective measure of retinal function, serving as an important diagnostic clinical tool in ophthalmology for evaluating the integrity of the retina. Given the similarity between the anatomy and physiology of the human and Green Monkey eyes, this species has increasingly become a favorable non-human primate model for assessing ocular defects in humans. To test this model, we obtained full-field electroretinographic recordings (ERG) and normal values for standard responses required by the International Society for Clinical Electrophysiology of Vision (ISCEV). Photopic and scotopic ERG recordings were obtained by full-field stimulation over a range of 6 log units of intensity in dark-adapted or light-adapted eyes of adult Green Monkeys (Chlorocebus sabaeus). Intensity, duration, and interval of light stimuli were varied separately. Reproducible values of amplitude and latency were obtained for the a- and b-waves, under well-controlled adaptation and stimulus conditions; the i-wave was also easily identifiable and separated from the a-b-wave complex in the photopic ERG. The recordings obtained in the healthy Green Monkey matched very well with those in humans and other non-human primate species (Macaca mulatta and Macaca fascicularis). These results validate the Green Monkey as an excellent non-human primate model, with potential to serve for testing retinal function following various manipulations such as visual deprivation or drug evaluation. PMID:25360686

PrimaTB STAT-PAK Assay, a Novel, Rapid Lateral-Flow Test for Tuberculosis in Nonhuman Primates▿

PubMed Central

Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Greenwald, David; Nacy, Carol A.; Gibson, Susan; Didier, Peter J.; Washington, Marc; Szczerba, Peter; Motzel, Sherri; Handt, Larry; Pollock, John M.; McNair, James; Andersen, Peter; Langermans, Jan A. M.; Verreck, Frank; Ervin, Sean; Ervin, Frank; McCombs, Candace

2007-01-01

Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP. PMID:17652522

Can Monkeys Make Investments Based on Maximized Pay-off?

PubMed Central

Steelandt, Sophie; Dufour, Valérie; Broihanne, Marie-Hélène; Thierry, Bernard

2011-01-01

Animals can maximize benefits but it is not known if they adjust their investment according to expected pay-offs. We investigated whether monkeys can use different investment strategies in an exchange task. We tested eight capuchin monkeys (Cebus apella) and thirteen macaques (Macaca fascicularis, Macaca tonkeana) in an experiment where they could adapt their investment to the food amounts proposed by two different experimenters. One, the doubling partner, returned a reward that was twice the amount given by the subject, whereas the other, the fixed partner, always returned a constant amount regardless of the amount given. To maximize pay-offs, subjects should invest a maximal amount with the first partner and a minimal amount with the second. When tested with the fixed partner only, one third of monkeys learned to remove a maximal amount of food for immediate consumption before investing a minimal one. With both partners, most subjects failed to maximize pay-offs by using different decision rules with each partner' quality. A single Tonkean macaque succeeded in investing a maximal amount to one experimenter and a minimal amount to the other. The fact that only one of over 21 subjects learned to maximize benefits in adapting investment according to experimenters' quality indicates that such a task is difficult for monkeys, albeit not impossible. PMID:21423777

Perceived control in rhesus monkeys (Macaca mulatta) - Enhanced video-task performance

NASA Technical Reports Server (NTRS)

Washburn, David A.; Hopkins, William D.; Rumbaugh, Duane M.

1991-01-01

This investigation was designed to determine whether perceived control effects found in humans extend to rhesus monkeys (Macaca mulatta) tested in a video-task format, using a computer-generated menu program, SELECT. Choosing one of the options in SELECT resulted in presentation of five trials of a corresponding task and subsequent return to the menu. In Experiments 1-3, the animals exhibited stable, meaningful response patterns in this task (i.e., they made choices). In Experiment 4, performance on tasks that were selected by the animals significantly exceeded performance on identical tasks when assigned by the experimenter under comparable conditions (e.g., time of day, order, variety). The reliable and significant advantage for performance on selected tasks, typically found in humans, suggests that rhesus monkeys were able to perceive the availability of choices.

Young macaques (Macaca fascicularis) preferentially bias attention towards closer, older, and better tool users.

PubMed

Tan, Amanda W Y; Hemelrijk, Charlotte K; Malaivijitnond, Suchinda; Gumert, Michael D

2018-05-12

Examining how animals direct social learning during skill acquisition under natural conditions, generates data for examining hypotheses regarding how transmission biases influence cultural change in animal populations. We studied a population of macaques on Koram Island, Thailand, and examined model-based biases during interactions by unskilled individuals with tool-using group members. We first compared the prevalence of interactions (watching, obtaining food, object exploration) and proximity to tool users during interactions, in developing individuals (infants, juveniles) versus mature non-learners (adolescents, adults), to provide evidence that developing individuals are actively seeking information about tool use from social partners. All infants and juveniles, but only 49% of mature individuals carried out interacted with tool users. Macaques predominantly obtained food by scrounging or stealing, suggesting maximizing scrounging opportunities motivates interactions with tool users. However, while interactions by adults was limited to obtaining food, young macaques and particularly infants also watched tool users and explored objects, indicating additional interest in tool use itself. We then ran matrix correlations to identify interaction biases, and what attributes of tool users influenced these. Biases correlated with social affiliation, but macaques also preferentially targeted tool users that potentially increase scrounging and learning opportunities. Results suggest that social structure may constrain social learning, but the motivation to bias interactions towards tool users to maximize feeding opportunities may also socially modulate learning by facilitating close proximity to better tool users, and further interest in tool-use actions and materials, especially during development.

The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

PubMed

Kanthaswamy, S; Ng, J; Satkoski Trask, J; George, D A; Kou, A J; Hoffman, L N; Doherty, T B; Houghton, P; Smith, D G

2013-06-01

The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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.

Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

PubMed

Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

2002-08-01

Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

Resolution of the African hominoid trichotomy by use of a mitochondrial gene sequence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruvolo, M.; Disotell, T.R.; Allard, M.W.

1991-02-15

Mitochondrial DNA sequences encoding the cytochrome oxidase subunit II gene have been determined for five primate species, siamang (Hylobates syndactylus), lowland gorilla (Gorilla gorilla), pygmy chimpanzee (Pan paniscus), crab-eating macaque (Macaca fascicularis), and green monkey (Cercopithecus aethiops), and compared with published sequences of other primate and nonprimate species. Comparisons of cytochrome oxidase subunit II gene sequences provide clear-cut evidence from the mitochondrial genome for the separation of the African ape trichotomy into two evolutionary lineages, one leading to gorillas and the other to humans and chimpanzees. Several different tree-building methods support this same phylogenetic tree topology. The comparisons also yieldmore » trees in which a substantial length separates the divergence point of gorillas from that of humans and chimpanzees, suggesting that the lineage most immediately ancestral to humans and chimpanzees may have been in existence for a relatively long time.« less

Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox.

PubMed

Johnson, Reed F; Yellayi, Srikanth; Cann, Jennifer A; Johnson, Anthony; Smith, Alvin L; Paragas, Jason; Jahrling, Peter B; Blaney, Joseph E

2011-09-30

Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease within 12 days post-inoculation in two independent experiments. Clinical observations and hematological and histopathological findings support hemorrhagic disease. Cowpox virus replicated to high levels in blood (8.0-9.0 log(10) gene copies/mL) and tissues including lymph nodes, thymus, spleen, bone marrow, and lungs. This unique model of hemorrhagic orthopoxvirus infection provides an accessible means to further study orthopoxvirus pathogenesis and to identify virus-specific and nonspecific therapies. Such studies will serve to complement the existing nonhuman primate models of more classical poxviral disease. Published by Elsevier Inc.

Differential regulation of amyloid-. beta. -protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, G.A.; Lewis, D.A.; Bahmanyar, S.

1988-02-01

The authors have mapped the neuroanatomical distribution of amyloid-..beta..-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-..beta..-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In the central nervous system of monkey and normal aged human, image analysis shows that neurons of the dentate gyrus and cornu Ammonis fields contain a 2.5-times-greater hybridization signal than is present in neurons of the subiculum and entorhinal cortex. In contrast, in the Alzheimer disease hippocampal formation, the levels of amyloid-..beta..-protein mRNAmore » in the cornu Ammonis field 3 and parasubiculum are equivalent. These findings suggest that within certain neuronal subpopulations cell type-specific regulation of amyloid-..beta..-protein gene expression may be altered in Alzheimer disease.« less

Computer-task testing of rhesus monkeys (Macaca mulatta) in the social milieu.

PubMed

Washburn, D A; Harper, S; Rumbaugh, D M

1994-07-01

Previous research has demonstrated that a behavior and performance testing paradigm, in which rhesus monkeys (Macaca mulatta) manipulate a joystick to respond to computer-generated stimuli, provides environmental enrichment and supports the psychological well-being of captive research animals. The present study was designed to determine whether computer-task activity would be affected by pair-housing animals that had previously been tested only in their single-animal home cages. No differences were observed in productivity or performance levels as a function of housing condition, even when the animals were required to "self-identify" prior to performing each trial. The data indicate that cognitive challenge and control are as preferred by the animals as social opportunities, and that, together with comfort/health considerations, each must be addressed for the assurance of psychological well-being.

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

PubMed

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.

Effects of competition on video-task performance in monkeys (Macaca mulatta)

NASA Technical Reports Server (NTRS)

Washburn, David A.; Hopkins, William D.; Rumbaugh, Duane M.

1990-01-01

The effects of competition on performance of a video-formatted task were examined in a series of experiments. Two rhesus monkeys (Macaca mulatta) were trained to manipulate a joystick to shoot at moving targets on a computer screen. The task was made competitive by requiring both animals to shoot at the same target and by rewarding only the animal that hit the target first each trial. The competitive task produced a significant and robust speed-accuracy trade-off in performance. The monkeys hit the target in significantly less time on contested than on uncontested trials. However, they required significantly more shots to hit the target on contested trials in relation to uncontested trials. This effect was unchanged when various schedules of reinforcement were introduced in the uncontested trials. This supports the influence of competition qua competition on performance, a point further bolstered by other findings of behavioral contrast presented here.

Personality of Wild Male Crested Macaques (Macaca nigra)

PubMed Central

Neumann, Christof; Agil, Muhammad; Widdig, Anja; Engelhardt, Antje

2013-01-01

Animal personalities, i.e. consistent differences in behavior across time and/or context, have received increased attention of behavioral biologists over the last years. Recent research shows that personalities represent traits on which natural and sexual selection work and which can have substantial fitness consequences. The aim of this study is to establish the personality structure of crested macaque (Macaca nigra) males as foundation for future studies on its adaptive value. We collected behavioral data through focal animal sampling and additionally conducted two sets of playback experiments. Results of a factor analysis on the behavioral data revealed a four factor structure with components we labeled Anxiety, Sociability, Connectedness and Aggressiveness. Results from the experiments revealed an additional and independent Boldness factor but the absence of Neophilia. Overall, this structure resembles other macaque and animal species with the exception of Connectedness, which might be a consequence of the species' tolerant social style. Our results thus not only form the basis for future studies on the adaptive value of personality in crested macaques but also contribute an important data point for investigating the evolution of personality structure from a comparative perspective by refining, for example, which personality factors characterized the last common ancestor of hominids and macaques. PMID:23940517

Nonhuman primate infections after organ transplantation.

PubMed

Haustein, Silke V; Kolterman, Amanda J; Sundblad, Jeffrey J; Fechner, John H; Knechtle, Stuart J

2008-01-01

Nonhuman primates, primarily rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and baboons (Papio spp.), have been used extensively in research models of solid organ transplantation, mainly because the nonhuman primate (NHP) immune system closely resembles that of the human. Nonhuman primates are also frequently the model of choice for preclinical testing of new immunosuppressive strategies. But the management of post-transplant nonhuman primates is complex, because it often involves multiple immunosuppressive agents, many of which are new and have unknown effects. Additionally, the resulting immunosuppression carries a risk of infectious complications, which are challenging to diagnose. Last, because of the natural tendency of animals to hide signs of weakness, infectious complications may not be obvious until the animal becomes severely ill. For these reasons the diagnosis of infectious complications is difficult among post-transplant NHPs. Because most nonhuman primate studies in organ transplantation are quite small, there are only a few published reports concerning infections after transplantation in nonhuman primates. Based on our survey of these reports, the incidence of infection in NHP transplant models is 14%. The majority of reports suggest that many of these infections are due to reactivation of viruses endemic to the primate species, such as cytomegalovirus (CMV), polyomavirus, and Epstein-Barr virus (EBV)-related infections. In this review, we address the epidemiology, pathogenesis, role of prophylaxis, clinical presentation, and treatment of infectious complications after solid organ transplantation in nonhuman primates.

Nonhuman Primate Infections after Organ Transplantation

PubMed Central

Haustein, Silke V.; Kolterman, Amanda J.; Sundblad, Jeffrey J.; Fechner, John H.; Knechtle, Stuart J.

2016-01-01

Nonhuman primates, primarily rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and baboons (Papio spp.), have been used extensively in research models of solid organ transplantation, mainly because the nonhuman primate (NHP) immune system closely resembles that of the human. Nonhuman primates are also frequently the model of choice for preclinical testing of new immunosuppressive strategies. But the management of post-transplant nonhuman primates is complex, because it often involves multiple immunosuppressive agents, many of which are new and have unknown effects. Additionally, the resulting immunosuppression carries a risk of infectious complications, which are challenging to diagnose. Last, because of the natural tendency of animals to hide signs of weakness, infectious complications may not be obvious until the animal becomes severely ill. For these reasons the diagnosis of infectious complications is difficult among post-transplant NHPs. Because most nonhuman primate studies in organ transplantation are quite small, there are only a few published reports concerning infections after transplantation in nonhuman primates. Based on our survey of these reports, the incidence of infection in NHP transplant models is 14%. The majority of reports suggest that many of these infections are due to reactivation of viruses endemic to the primate species, such as cytomegalovirus (CMV), polyomavirus, and Epstein-Barr virus (EBV)–related infections. In this review, we address the epidemiology, pathogenesis, role of prophylaxis, clinical presentation, and treatment of infectious complications after solid organ transplantation in nonhuman primates. PMID:18323582

Reduced Marker of Vascularization in the Anterior Hippocampus in a Female Monkey Model of Depression

PubMed Central

Kalidindi, Anisha; Kelly, Sean D.; Singleton, Kaela S.; Guzman, Dora; Merrill, Liana; Willard, Stephanie L.; Shively, Carol A.; Neigh, Gretchen N.

2016-01-01

Depression is a common and debilitating mood disorder that impacts women more often than men. The mechanisms that result in depressive behaviors are not fully understood; however, the hippocampus has been noted as a key structure in the pathophysiology of depression. In addition to neural implications of depression, the cardiovascular system is impacted. Although not as commonly considered, the cerebrovasculature is critical to brain function, impacted by environmental stimuli, and is capable of altering neural function and thereby behavior. In the current study, we assessed the relationship between depressive behavior and a marker of vascularization of the hippocampus in adult female cynomolgus macaques (Macaca fascicularis). Similar to previously noted impacts on neuropil and glia, the depressed phenotype predicts a reduction in a marker of vascular length in the anterior hippocampus. These data reinforce the growing recognition of the effects of depression on vasculature and support further consideration of vascular endpoints in studies aimed at the elucidation of the mechanisms underlying depression. PMID:27423324

Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.

PubMed

Kavanagh, Kylie; Koudy Williams, J; Wagner, Janice D

2005-08-01

Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.

Human Exposure to Herpesvirus B–Seropositive Macaques, Bali, Indonesia

PubMed Central

Engel, Gregory A.; Schillaci, Michael A.; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

2002-01-01

Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a “monkey forest” (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B. PMID:12141963

Goal attribution to inanimate moving objects by Japanese macaques (Macaca fuscata)

PubMed Central

Atsumi, Takeshi; Koda, Hiroki; Masataka, Nobuo

2017-01-01

Humans interpret others’ goals based on motion information, and this capacity contributes to our mental reasoning. The present study sought to determine whether Japanese macaques (Macaca fuscata) perceive goal-directedness in chasing events depicted by two geometric particles. In Experiment 1, two monkeys and adult humans were trained to discriminate between Chasing and Random sequences. We then introduced probe stimuli with various levels of correlation between the particle trajectories to examine whether participants performed the task using higher correlation. Participants chose stimuli with the highest correlations by chance, suggesting that correlations were not the discriminative cue. Experiment 2 examined whether participants focused on particle proximity. Participants differentiated between Chasing and Control sequences; the distance between two particles was identical in both. Results indicated that, like humans, the Japanese macaques did not use physical cues alone to perform the discrimination task and integrated the cues spontaneously. This suggests that goal attribution resulting from motion information is a widespread cognitive phenotype in primate species. PMID:28053305

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

PubMed Central

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

Sexual dimorphism of sulcal length asymmetry in the cerebrum of adult cynomolgus monkeys (Macaca fascicularis).

PubMed

Imai, Noritaka; Sawada, Kazuhiko; Fukunishi, Katsuhiro; Sakata-Haga, Hiromi; Fukui, Yoshihiro

2011-12-01

The present study aimed to quantitatively clarify the gross anatomical asymmetry and sexual dimorphism of the cerebral hemispheres of cynomolgus monkeys. While the fronto-occipital length of the right and left cerebral hemispheres was not different between sexes, a statistically significant rightward asymmetry was detected in the cerebral width at the perisylvian region in females, but not in males (narrower width of the left side in the females). An asymmetry quotient of the sulcal lengths revealed a rightward asymmetry in the inferior occipital sulcus and a leftward asymmetry in the central and intraparietal sulci in both sexes. However, the laterality of the lengths of other sulci was different for males and females. The arcuate sulcus was directed rightward in males but there was no rightward bias in females. Interestingly, the principle sulcus and lateral fissure were left-lateralized in the males, but right-lateralized in the females. The results suggest that lateralization patterns are regionally and sexually different in the cerebrum of cynomolgus monkeys. The present results provide a reference for quantitatively evaluating the normality of the cerebral cortical morphology in cynomolgus monkeys. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

Rotational displacement skills in rhesus macaques (Macaca mulatta).

PubMed

Hughes, Kelly D; Santos, Laurie R

2012-11-01

Rotational displacement tasks, in which participants must track an object at a hiding location within an array while the array rotates, exhibit a puzzling developmental pattern in humans. Human children take an unusually long time to master this task and tend to solve rotational problems through the use of nongeometric features or landmarks as opposed to other kinds of spatial cues. We investigated whether these developmental characteristics are unique to humans by testing rotational displacement skills in a monkey species, the rhesus macaque (Macaca mulatta), using a looking-time method. Monkeys first saw food hidden in two differently colored boxes within an array. The array was then rotated 180° and the boxes reopened to reveal the food in an expected or unexpected location. Our first two experiments explored the developmental time-course of performance on this rotational displacement task. We found that adult macaques looked longer at the unexpected event, but such performance was not mirrored in younger-aged macaques. In a third study, we systematically varied featural information and visible access to the array to investigate which strategies adult macaques used in solving rotational displacements. Our results show that adult macaques need both sets of information to solve the task. Taken together, these results suggest both similarities and differences in mechanisms by which human and nonhuman primates develop this spatial skill.

Rotational Displacement Skills in Rhesus Macaques (Macaca mulatta)

PubMed Central

Hughes, Kelly D.; Santos, Laurie R.

2016-01-01

Rotational displacement tasks, in which participants must track an object at a hiding location within an array while the array rotates, exhibit a puzzling developmental pattern in humans. Human children take an unusually long time to master this task and tend to solve rotational problems through the use of nongeometric features or landmarks as opposed to other kinds of spatial cues. We investigated whether these developmental characteristics are unique to humans by testing rotational displacement skills in a monkey species, the rhesus macaque (Macaca mulatta), using a looking-time method. Monkeys first saw food hidden in two differently colored boxes within an array. The array was then rotated 180° and the boxes reopened to reveal the food in an expected or unexpected location. Our first two experiments explored the developmental time-course of performance on this rotational displacement task. We found that adult macaques looked longer at the unexpected event, but such performance was not mirrored in younger-aged macaques. In a third study, we systematically varied featural information and visible access to the array to investigate which strategies adult macaques used in solving rotational displacements. Our results show that adult macaques need both sets of information to solve the task. Taken together, these results suggest both similarities and differences in mechanisms by which human and nonhuman primates develop this spatial skill. PMID:22866770

Impaired performance from brief social isolation of rhesus monkeys (Macaca mulatta) - A multiple video-task assessment

NASA Technical Reports Server (NTRS)

Washburn, David A.; Rumbaugh, Duane M.

1991-01-01

Social isolation has been demonstrated to produce profound and lasting psychological effects in young primates. In the present investigation, two adult rhesus monkeys (Macaca mulatta) were isolated from one another for up to 6 days and tested on 7 video tasks designed to assess psychomotor and cognitive functioning. Both the number and quality (i.e., speed and accuracy) of responses were significantly compromised in the social isolation condition relative to levels in which the animals were tested together. It is argued that adult rhesus are susceptible to performance disruption by even relatively brief social isolation, and that these effects can best be assessed by a battery of complex and sensitive measures.

Socialization in Pigtailed Macaques (Macaca nemestrina)

PubMed Central

WORLEIN, JULIE M.; KROEKER, ROSE; LEE, GRACE H.; THOM, JINHEE P.; BELLANCA, RITA U.; CROCKETT, CAROLYN M.

2018-01-01

In response to new emphasis by regulatory agencies regarding socialization, behavioral management programs are allocating greater resources to maximize socialization opportunities for laboratory primates. Information regarding predictors of compatibility and risk of injury for all laboratory-housed species of macaques are needed to make social introductions and pairings as efficient and safe as possible. This study presents data on 674 pairs of pigtailed macaques (Macaca nemestrina) at the Washington National Primate Research Center over a 7-year period. During pair introduction, behavior was monitored while the degree of tactile contact was gradually increased. Based on observed behavior, pairs were assigned a behavioral introduction score (BIS), rating the quality of their interactions for each day of introduction. Animals deemed compatible, based on the BIS and technologist judgment, were allowed to progress to continuous contact with no staff present. A small proportion of animals deemed compatible at introduction was later separated for subsequent incompatibility or aggression; these proportions were higher in full contact compared to protected contact pairings. Of 674 pairs, 75% were deemed compatible at introduction in protected contact; 86 of these pairs were later transitioned to full contact with 98% compatibility. Predictors of decreased compatibility assessed during protected contact introductions included age (adult pairs were less compatible), the BIS on the last day of introduction, and aggression or injury during the introductory period. Predictors of injuries during the protected contact introduction process included: aggression on the first day of introduction, a negative BIS on the first or last day of introduction, and, surprisingly, the presence of grooming on the first day of introduction. Injuries during both introduction and subsequent pairing in protected contact were rare; however, injury rates increased significantly during full

[Ultrastructural observation on nymphal Armillifer sp. by scanning electron microscopy and phylogenetic analysis based on 18S rRNA].

PubMed

Li, Jian; Shi, Yun-Liang; Shi, Wei; Fang, Fang; Zhou, Qing-An; Li, Wen-Wen; He, Guo-Sheng; Huang, Wei-Yi

2012-04-30

To observe the ultrastructure of nymphal Armillifer sp. isolated from Macaca fascicularis by using scanning electron microscope (SEM), and analyze the phylogenetic relationships based on 18S rRNA gene sequences. The parasite samples stored in 70% alcohol were fixed by glutaraldehyde and osmium peroxide. Ultrastructural characters of those samples were observed under SEM. Amplification and sequencing of the 18S rRNA gene were performed following the extraction of total genome DNA. Sequence analysis was performed based on multiple alignment using ClustalX1.83, while phylogenetic analysis was made by Neighbor-Joining method using MEGA4.0. The nymphs were in cylindrical shape, the body slightly claviform tapering to posterior end. Abdominal annuli were gradually widened from anterior to posterior parts, the 12th-13th abdominal annuli of which were similar in width. The annuli ranged closer in the front half body, whereas in the latter part there were certain gaps between them. The circular-shaped mouth located in the middle of head ventrally. Folds were seen in inner margin of the mouth with a pair of curved hooks on both sides above it which practically disposed in a straight line. Two pairs of large sensory papillae were observed symmetrically over the last thoracic annulus of cephalothoraxs lying below the outer hook, and the first abdominal annulus was near the median ventral line. The number of abdominal annuli was 29, not including 2 incomplete terminal annuli. Rounded sensory papillae were fully distributed on the body surface, except the dorsal side of head and the ventral part of the terminal annulus. Agglomerate-like anus opening was observed at the end of ventral abdominal annuli and distinctly sub-terminal. These morphological features demonstrated that the nymphs were highly similar with that of Armillifer moniliformis Diesing, 1835. A fragment of 18SrRNA gene (1 836 bp) sequences was obtained by PCR combined with sequencing, and was registered to the Gene

Collective Movement in the Tibetan Macaques (Macaca thibetana): Early Joiners Write the Rule of the Game.

PubMed

Wang, Xi; Sun, Lixing; Li, Jinhua; Xia, Dongpo; Sun, Binghua; Zhang, Dao

2015-01-01

Collective behavior has recently attracted a great deal of interest in both natural and social sciences. While the role of leadership has been closely scrutinized, the rules used by joiners in collective decision making have received far less attention. Two main hypotheses have been proposed concerning these rules: mimetism and quorum. Mimetism predicts that individuals are increasingly likely to join collective behavior as the number of participants increases. It can be further divided into selective mimetism, where relationships among the participants affect the process, and anonymous mimetism, where no such effect exists. Quorum predicts that a collective behavior occurs when the number of participants reaches a threshold. To probe into which rule is used in collective decision making, we conducted a study on the joining process in a group of free-ranging Tibetan macaques (Macaca thibetana) in Huangshan, China using a combination of all-occurrence and focal animal sampling methods. Our results show that the earlier individuals joined movements, the more central a role they occupied among the joining network. We also found that when less than three adults participated in the first five minutes of the joining process, no entire group movement occurred subsequently. When the number of these early joiners ranged from three to six, selective mimetism was used. This means higher rank or closer social affiliation of early joiners could be among the factors of deciding whether to participate in movements by group members. When the number of early joiners reached or exceeded seven, which was the simple majority of the group studied, entire group movement always occurred, meaning that the quorum rule was used. Putting together, Macaca thibetana used a combination of selective mimetism and quorum, and early joiners played a key role in deciding which rule should be used.

Collective Movement in the Tibetan Macaques (Macaca thibetana): Early Joiners Write the Rule of the Game

PubMed Central

Li, Jinhua; Xia, Dongpo; Sun, Binghua; Zhang, Dao

2015-01-01

Collective behavior has recently attracted a great deal of interest in both natural and social sciences. While the role of leadership has been closely scrutinized, the rules used by joiners in collective decision making have received far less attention. Two main hypotheses have been proposed concerning these rules: mimetism and quorum. Mimetism predicts that individuals are increasingly likely to join collective behavior as the number of participants increases. It can be further divided into selective mimetism, where relationships among the participants affect the process, and anonymous mimetism, where no such effect exists. Quorum predicts that a collective behavior occurs when the number of participants reaches a threshold. To probe into which rule is used in collective decision making, we conducted a study on the joining process in a group of free-ranging Tibetan macaques (Macaca thibetana) in Huangshan, China using a combination of all-occurrence and focal animal sampling methods. Our results show that the earlier individuals joined movements, the more central a role they occupied among the joining network. We also found that when less than three adults participated in the first five minutes of the joining process, no entire group movement occurred subsequently. When the number of these early joiners ranged from three to six, selective mimetism was used. This means higher rank or closer social affiliation of early joiners could be among the factors of deciding whether to participate in movements by group members. When the number of early joiners reached or exceeded seven, which was the simple majority of the group studied, entire group movement always occurred, meaning that the quorum rule was used. Putting together, Macaca thibetana used a combination of selective mimetism and quorum, and early joiners played a key role in deciding which rule should be used. PMID:25992882

The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey.

PubMed

Wang, Yiwen; Danilova, Vicktoria; Cragin, Tiffany; Roberts, Thomas W; Koposov, Alexey; Hellekant, Göran

2009-02-18

Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers. We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers. In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non

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'.

PubMed

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).

Mammalian spinal biomechanics: postural support in seated macaques.

PubMed

Gal, Julianna

2002-06-01

The aim of this study was to investigate whether the ligamentous lumbar vertebral column of a macaque could potentially provide passive mechanical support to the weight of the head, upper body and forelimbs during upright sitting. The seated flexed curvature of the lumbar spine of Macaca sylvana was estimated from a photograph and was partitioned equally among the lumbar-lumbar intervertebral joints. This flexed curvature was compared with the hyper-extended profile of the unloaded excised ligamentous spine of a related species (Macaca fascicularis) and used to calculate changes in intervertebral angle from the unloaded excised state to the loaded in vivo state. Changes in intervertebral angle were then used to calculate the net flexion moment required to bend the spine from the unloaded curvature to the seated curvature. The moment arm of the ventrally displaced weight of the head, upper body and forelimbs was estimated and used to calculate a corresponding net force. It was found that this force corresponded to approximately 18 % of the total body weight of the 2.34 kg sample animal. This compares with a likely fractional body weight of approximately 30-40 % for the head, upper body and forelimbs of these primates. Therefore, approximately half of the ventral flexion moment associated with the combined weight of the head, upper body and forelimbs during sitting in these animals may be supported by the passive mechanical properties associated with the ligamentous lumbar spine. This represents a potential means of relieving muscular effort and saving metabolic energy.

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

PubMed

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

2015-01-01

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

Different neural strategies for multimodal integration: comparison of two macaque monkey species.

PubMed

Sadeghi, Soroush G; Mitchell, Diana E; Cullen, Kathleen E

2009-05-01

The integration of neck proprioceptive and vestibular inputs underlies the generation of accurate postural and motor control. Recent studies have shown that central mechanisms underlying the integration of these sensory inputs differ across species. Notably, in rhesus monkey (Macaca mulata), an Old World monkey, neurons in the vestibular nuclei are insensitive to passive stimulation of neck proprioceptors. In contrast, in squirrel monkey, a New World monkey, stimulation produces robust modulation. This has led to the suggestion that there are differences in how sensory information is integrated during self-motion in Old versus New World monkeys. To test this hypothesis, we recorded from neurons in the vestibular nuclei of another species in the Macaca genus [i.e., M. fascicularis (cynomolgus monkey)]. Recordings were made from vestibular-only (VO) and position-vestibular-pause (PVP) neurons. The majority (53%) of neurons in both groups were sensitive to neck proprioceptive and vestibular stimulation during passive body-under-head and whole-body rotation, respectively. Furthermore, responses during passive rotations of the head-on-body were well predicted by the linear summation of vestibular and neck responses (which were typically antagonistic). During active head movement, the responses of VO and PVP neurons were further attenuated (relative to a model based on linear summation) for the duration of the active head movement or gaze shift, respectively. Taken together, our findings show that the brain's strategy for the central processing of sensory information can vary even within a single genus. We suggest that similar divergence may be observed in other areas in which multimodal integration occurs.

Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

PubMed

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. © 2016 Wiley Periodicals, Inc.

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

NASA Technical Reports Server (NTRS)

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.

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

PubMed

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. © The Author(s) 2016.

Cryopreservation of Cynomolgus Macaque (Macaca fascicularis) Sperm by Using a Commercial Egg-Yolk–Free Freezing Medium

PubMed Central

Yan, Yaping; Ao, Lei; Wang, Hong; Duan, Yanchao; Chang, Shaohui; Chen, Bingbing; Zhi, Dalong; Li, Sujuan; Niu, Yuyu; Ji, Weizhi; Si, Wei

2016-01-01

Conventional TRIS–egg yolk (TEY) freezing medium for the cryopreservation of NHP sperm has the risk of contamination due to widespread zoonotic diseases. This study was aimed at determining the optimal glycerol concentration, freezing rate, and holding time in liquid N2 vapor for the cryopreservation of cynomolgus macaque sperm by using a commercial egg-yolk–free freezing medium (SC medium) designed for human sperm cryopreservation. Sperm motility and acrosomal integrity after freezing were assessed. Sperm in SC medium (dilution ratio, 3:1) frozen at cooling rates of –67° and –183°C/min in liquid N2 vapor showed higher post-thaw motility than did samples frozen at –435 °C/min. At the cooling rate of –183 °C/min and dilution in SC medium at a 3:1 ratio, post-thaw motility was higher after a holding time of 10 min than after 30 min (recommended by the manufacturer). In addition, post-thaw motility of sperm frozen in SC medium was higher with dilution ratios of 3:1, 4.5:1, and 6:1 compared with 9:1, 10.5:1, and 12:1, and the sample diluted 12:1 showed the lowest percentage of thawed sperm with intact acrosomes. Sperm showed higher post-thaw motility after freezing in TEY than in SC medium; acrosomal integrity did not differ between the 2 media. Our results indicated that cynomolgus macaque sperm can be cryopreserved successfully by using a commercial egg-yolk–free freezing medium, which provides an option for genetic preservation with decreased zoonotic risk in this important NHP species. PMID:27931311

Cryopreservation of Cynomolgus Macaque (Macaca fascicularis) Sperm by Using a Commercial Egg-YolkFree Freezing Medium.

PubMed

Yan, Yaping; Ao, Lei; Wang, Hong; Duan, Yanchao; Chang, Shaohui; Chen, Bingbing; Zhi, Dalong; Li, Sujuan; Niu, Yuyu; Ji, Weizhi; Si, Wei

2016-11-01

Conventional TRISegg yolk (TEY) freezing medium for the cryopreservation of NHP sperm has the risk of contamination due to widespread zoonotic diseases. This study was aimed at determining the optimal glycerol concentration, freezing rate, and holding time in liquid N2 vapor for the cryopreservation of cynomolgus macaque sperm by using a commercial egg-yolkfree freezing medium (SC medium) designed for human sperm cryopreservation. Sperm motility and acrosomal integrity after freezing were assessed. Sperm in SC medium (dilution ratio, 3:1) frozen at cooling rates of 67 and 183C/min in liquid N2 vapor showed higher post-thaw motility than did samples frozen at 435C/min. At the cooling rate of 183C/min and dilution in SC medium at a 3:1 ratio, post-thaw motility was higher after a holding time of 10 min than after 30 min (recommended by the manufacturer). In addition, post-thaw motility of sperm frozen in SC medium was higher with dilution ratios of 3:1, 4.5:1, and 6:1 compared with 9:1, 10.5:1, and 12:1, and the sample diluted 12:1 showed the lowest percentage of thawed sperm with intact acrosomes. Sperm showed higher post-thaw motility after freezing in TEY than in SC medium; acrosomal integrity did not differ between the 2 media. Our results indicated that cynomolgus macaque sperm can be cryopreserved successfully by using a commercial egg-yolkfree freezing medium, which provides an option for genetic preservation with decreased zoonotic risk in this important NHP species.

Costs of mate-guarding in wild male long-tailed macaques (Macaca fascicularis): physiological stress and aggression.

PubMed

Girard-Buttoz, Cédric; Heistermann, Michael; Rahmi, Erdiansyah; Agil, Muhammad; Fauzan, Panji Ahmad; Engelhardt, Antje

2014-09-01

Mate-guarding is an important determinant of male reproductive success in a number of species. However, it is known to potentially incur costs. The aim of the present study was to assess the effect of mate-guarding on male physiological stress and aggression in long-tailed macaques, a species in which males mate-guard females to a lesser extent than predicted by the Priority of Access model (PoA). The study was carried out during two mating periods on three groups of wild long-tailed macaques in Indonesia by combining behavioral observations with non-invasive measurements of fecal glucocorticoid (fGC) levels. Mate-guarding was associated with a general rise in male stress hormone levels but, from a certain threshold of mate-guarding onwards, increased vigilance time was associated with a decrease in stress hormone output. Mate-guarding also increased male-male aggression rate and male vigilance time. Overall, alpha males were more physiologically stressed than other males independently of mating competition. Increased glucocorticoid levels during mate-guarding are most likely adaptive since it may help males to mobilize extra-energy required for mate-guarding and ultimately maintain a balanced energetic status. However, repeated exposure to high levels of stress over an extended period is potentially deleterious to the immune system and thus may carry costs. This potential physiological cost together with the cost of increased aggression mate-guarding male face may limit the male's ability to mate-guard females, explaining the deviance from the PoA model observed in long-tailed macaques. Comparing our results to previous findings we discuss how ecological factors, reproductive seasonality and rank achievement may modulate the extent to which costs of mate-guarding limit male monopolization abilities. Copyright © 2014. Published by Elsevier Inc.

Morphological integration of anatomical, developmental, and functional postcranial modules in the crab-eating macaque (Macaca fascicularis).

PubMed

Conaway, Mark A; Schroeder, Lauren; von Cramon-Taubadel, Noreen

2018-03-22

Integration and modularity reflect the coordinated action of past evolutionary processes and, in turn, constrain or facilitate phenotypic evolvability. Here, we analyze magnitudes of integration in the macaque postcranium to test whether 20 a priori defined modules are (1) more tightly integrated than random sets of postcranial traits, and (2) are differentiated based on mode of definition, with developmental modules expected to be more integrated than functional or anatomical modules. The 3D morphometric data collected for eight limb and girdle bones for 60 macaques were collated into anatomical, developmental, and functional modules. A resampling technique was used to create random samples of integration values for each module for statistical comparison. Our results found that not all a priori defined modules were more strongly integrated than random samples of postcranial traits and that specific types of modules did not present consistent patterns of integration. Rather, girdle and joint modules were consistently less integrated than limb modules, and forelimb elements were less integrated than hindlimbs. The results suggest that morphometrically complex modules tend to be less integrated than simple limb bones, irrespective of the number of available traits. However, differences in integration of the fore- and hindlimb more likely reflects the multitude of locomotory, feeding, and social functions involved. It remains to be tested whether patterns of integration identified here are primate universals, and to what extent they vary depending on phylogenetic or functional factors. © 2018 Wiley Periodicals, Inc.

Behavioral asymmetries of psychomotor performance in rhesus monkeys (Macaca mulatta) - A dissociation between hand preference and skill

NASA Technical Reports Server (NTRS)

Hopkins, William D.; Washburn, David A.; Berke, Leslie; Williams, Mary

1992-01-01

Hand preferences were recorded for 35 rhesus monkeys (Macaca mulatta) as they manipulated a joystick in response to 2 computerized tasks. These preferences were then used to contrast 8 left- and 10 right-handed subjects on performance measures of hand skill. Individual hand preferences were found, but no significant population asymmetry was observed across the sample. However, the performance data reveal substantial benefits of right-handedness for joystick manipulation, as this group of monkeys mastered the 2 psychomotor tasks significantly faster than did their left-handed counterparts. The data support earlier reports of a right-hand advantage for joystick manipulation and also support the importance of distinguishing between hand preference and manual performance in research on functional asymmetries.

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

PubMed

Ponce, R; Armstrong, K; Andrews, K; Hensler, J; Waggie, K; Heffernan, J; Reynolds, T; Rogge, M

2005-01-01

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

Effects of Bazedoxifene Alone and with Conjugated Equine Estrogens on Coronary and Peripheral Artery Atherosclerosis of Postmenopausal Monkeys

PubMed Central

Clarkson, Thomas B.; Ethun, Kelly F.; Chen, Haiying; Golden, Debbie; Floyd, Edison; Appt, Susan E.

2012-01-01

Objective The objective was to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atherosclerosis and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) in a monkey model. Methods Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and then randomized to receive no treatment, or women’s equivalent doses of BZA (20 mg/day), CEE (0.45 mg/day) or BZA+CEE. The experiment period was for 20 months (approximately equivalent to 5 years of patient experience) during which interim measures were made of cardiovascular risk factors. At the end of the experimental period, the extent and severity of coronary and iliac artery atherosclerosis was quantified. Results Body weight, adiposity, fasting glucose concentrations and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on coronary artery nor common iliac artery atherosclerosis extent or severity when compared to no-treatment. CEE, administered soon after inducing menopause, had a robust atheroprotective effect on both iliac and coronary artery extent and severity. The addition of BZA to the CEE treatment antagonized the atheroprotective effect of the CEE. Conclusions In this nonhuman primate trial, treatment with BZA alone, CEE alone and BZA and CEE in combination did not have significant effects on plasma lipid profiles. CEE markedly inhibited the progression and complication of both coronary and iliac artery atherosclerosis. BZA had no adverse effects on atherosclerosis but attenuated the atheroprotective effects of CEE. PMID:23435024

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.

PubMed

Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

2006-02-09

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.

Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes.

PubMed

Langley, Raymond J; Tipper, Jennifer L; Bruse, Shannon; Baron, Rebecca M; Tsalik, Ephraim L; Huntley, James; Rogers, Angela J; Jaramillo, Richard J; O'Donnell, Denise; Mega, William M; Keaton, Mignon; Kensicki, Elizabeth; Gazourian, Lee; Fredenburgh, Laura E; Massaro, Anthony F; Otero, Ronny M; Fowler, Vance G; Rivers, Emanuel P; Woods, Chris W; Kingsmore, Stephen F; Sopori, Mohan L; Perrella, Mark A; Choi, Augustine M K; Harrod, Kevin S

2014-08-15

Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis. To develop a biomarker panel to characterize sepsis in primates and ascertain its relevance to early diagnosis and progression of human sepsis. Intravenous inoculation of Macaca fascicularis with Escherichia coli produced mild to severe sepsis, lung injury, and death. Plasma samples were obtained before and after 1, 3, and 5 days of E. coli challenge and at the time of killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An integrative analysis of the metabolomic and transcriptomic datasets was performed to identify a panel of sepsis biomarkers. The extent of E. coli invasion, respiratory distress, lethargy, and mortality was dependent on the bacterial dose. Metabolomic and transcriptomic changes characterized severe infections and death, and indicated impaired mitochondrial, peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and plasma metabolome suggested impaired fatty acid catabolism regulated by peroxisome-proliferator activated receptor signaling. A representative four-metabolite model effectively diagnosed sepsis in primates (area under the curve, 0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82). A model of sepsis based on reciprocal metabolomic and transcriptomic data was developed in primates and validated in two human patient cohorts. It is anticipated that the identified parameters will facilitate early diagnosis and management of sepsis.

Macacine Herpesvirus 1 in Long-Tailed Macaques, Malaysia, 2009–2011

PubMed Central

Lee, Mei-Ho; Rostal, Melinda K.; Hughes, Tom; Sitam, Frankie; Lee, Chee-Yen; Japning, Jeffrine; Harden, Mallory E.; Griffiths, Anthony; Basir, Misliah; Wolfe, Nathan D.; Daszak, Peter

2015-01-01

Macacine herpesvirus 1 (MaHV1; B virus) naturally infects macaques (Macaca spp.) and can cause fatal encephalitis in humans. In Peninsular Malaysia, wild macaques are abundant, and translocation is used to mitigate human–macaque conflict. Most adult macaques are infected with MaHV1, although the risk for transmission to persons who handle them during capture and translocation is unknown. We investigated MaHV1 shedding among 392 long-tailed macaques (M. fascicularis) after capture and translocation by the Department of Wildlife and National Parks in Peninsular Malaysia, during 2009–2011. For detection of MaHV1 DNA, PCR was performed on urogenital and oropharyngeal swab samples. Overall, 39% of macaques were shedding MaHV1 DNA; rates of DNA detection did not differ between sample types. This study demonstrates that MaHV1 was shed by a substantial proportion of macaques after capture and transport and suggests that persons handling macaques under these circumstances might be at risk for exposure to MaHV1. PMID:26080081

Local field potential spectral tuning in motor cortex during reaching.

PubMed

Heldman, Dustin A; Wang, Wei; Chan, Sherwin S; Moran, Daniel W

2006-06-01

In this paper, intracortical local field potentials (LFPs) and single units were recorded from the motor cortices of monkeys (Macaca fascicularis) while they preformed a standard three-dimensional (3-D) center-out reaching task. During the center-out task, the subjects held their hands at the location of a central target and then reached to one of eight peripheral targets forming the corners of a virtual cube. The spectral amplitudes of the recorded LFPs were calculated, with the high-frequency LFP (HF-LFP) defined as the average spectral amplitude change from baseline from 60 to 200 Hz. A 3-D linear regression across the eight center-out targets revealed that approximately 6% of the beta LFPs (18-26 Hz) and 18% of the HF-LFPs were tuned for velocity (p-value < 0.05), while 10% of the beta LFPs and 15% of the HF-LFPs were tuned for position. These results suggest that a multidegree-of-freedom brain-machine interface is possible using high-frequency LFP recordings in motor cortex.

Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer.

PubMed

Liu, Zhen; Cai, Yijun; Wang, Yan; Nie, Yanhong; Zhang, Chenchen; Xu, Yuting; Zhang, Xiaotong; Lu, Yong; Wang, Zhanyang; Poo, Muming; Sun, Qiang

2018-02-08

Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys (Macaca fascicularis) by somatic cell nuclear transfer (SCNT). We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys. For SCNT using fetal monkey fibroblasts, 6 pregnancies were confirmed in 21 surrogates and yielded 2 healthy babies. For SCNT using adult monkey cumulus cells, 22 pregnancies were confirmed in 42 surrogates and yielded 2 babies that were short-lived. In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts. Copyright © 2018 Elsevier Inc. All rights reserved.

Resource depletion through primate stone technology

PubMed Central

Tan, Amanda; Haslam, Michael; Kulik, Lars; Proffitt, Tomos; Malaivijitnond, Suchinda; Gumert, Michael

2017-01-01

Tool use has allowed humans to become one of the most successful species. However, tool-assisted foraging has also pushed many of our prey species to extinction or endangerment, a technology-driven process thought to be uniquely human. Here, we demonstrate that tool-assisted foraging on shellfish by long-tailed macaques (Macaca fascicularis) in Khao Sam Roi Yot National Park, Thailand, reduces prey size and prey abundance, with more pronounced effects where the macaque population size is larger. We compared availability, sizes and maturation stages of shellfish between two adjacent islands inhabited by different-sized macaque populations and demonstrate potential effects on the prey reproductive biology. We provide evidence that once technological macaques reach a large enough group size, they enter a feedback loop – driving shellfish prey size down with attendant changes in the tool sizes used by the monkeys. If this pattern continues, prey populations could be reduced to a point where tool-assisted foraging is no longer beneficial to the macaques, which in return may lessen or extinguish the remarkable foraging technology employed by these primates. PMID:28884681

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

PubMed Central

Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

2016-01-01

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

Omental anatomy of non-human primates.

PubMed

Chaffanjon, Philippe C J; Kenyon, Norman M; Ricordi, Camillo; Kenyon, Norma S

2005-11-01

The anatomy and physiology of the omentum provide optimum reconstructive characteristics and the omentum may be used as a free or pedicled autograft, but also as the receptor site for engraftment of glandular islets. Our purpose was the study of the omental anatomy of non-human primate (NHP), in order to determine an experimental model for pancreatic islets transplantation. Seventeen cadavers NHP (age range 4 years to 23 years) were utilised in this anatomical study. Both cynomolgus monkeys (macaca fascicularis) and baboons (papio hamadryas) were analysed. The animals were without known medical or anatomical abnormalities. We studied the morphology of the omentum, with an emphasis on arterial vascularisation. The omental anatomy of the NHP is very similar to that of humans. The main difference lies in the shape of the lesser sac, which has a complete caudal recess. The arterial vascularisation has a double origin. Based on the anastomosis between them and on the vascular density, the NHP omentum can be divided into four vascular areas. Our results demonstrate that one or two long pedicled flaps can be constructed from the omentum.

Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes.

PubMed

Cheong, Clara Y; Chng, Keefe; Lim, Mei Kee; Amrithraj, Ajith I; Joseph, Roy; Sukarieh, Rami; Chee Tan, Yong; Chan, Louiza; Tan, Jun Hao; Chen, Li; Pan, Hong; Holbrook, Joanna D; Meaney, Michael J; Seng Chong, Yap; Gluckman, Peter D; Stünkel, Walter

2014-09-01

CXCL14 is a chemokine that has previously been implicated in insulin resistance in mice. In humans, the role of CXCL14 in metabolic processes is not well established, and we sought to determine whether CXCL14 is a risk susceptibility gene important in fetal programming of metabolic disease. For this purpose, we investigated whether CXCL14 is differentially regulated in human umbilical cords of infants with varying birth weights. We found an elevated expression of CXCL14 in human low birth weight (LBW) cords, as well as in cords from nutritionally restricted Macaca fascicularis macaques. To further analyze the regulatory mechanisms underlying the expression of CXCL14, we examined CXCL14 in umbilical cord-derived mesenchymal stem cells (MSCs) that provide an in vitro cell-based system amenable to experimental manipulation. Using both whole frozen cords and MSCs, we determined that site-specific CpG methylation in the CXCL14 promoter is associated with altered expression, and that changes in methylation are evident in LBW infant-derived umbilical cords that may indicate future metabolic compromise through CXCL14.

The Resin-Embedded Cornea Prepared Via Rapid Processing Protocol : A Good Histomorphometric Target for Clinical Investigation in Ophthalmology and Optometry

PubMed Central

Cheah, Pike See; Mohidin, Norhani; Mohd Ali, Bariah; Maung, Myint; Latif, Azian Abdul

2008-01-01

This study illustrates and quantifies the changes on corneal tissue between the paraffin-embedded and resin-embedded blocks and thus, selects a better target in investigational ophthalmology and optometry via light microscopy. Corneas of two cynomolgus monkeys (Macaca fascicularis) were used in this study. The formalin-fixed cornea was prepared in paraffin block via the conventional tissue processing protocol (4-day protocol) and stained with haematoxylin and eosin. The glutaraldehyde-fixed cornea was prepared in resin block via the rapid and modified tissue processing procedure (1.2-day protocol) and stained with toluidine blue. The paraffin-embedded sample exhibits various undesired tissue damage and artifact such as thinner epithelium (due to the substantial volumic extraction from the tissue), thicker stroma layer (due to the separation of lamellae and the presence of voids) and the distorted endothelium. In contrast, the resin-embedded corneal tissue has demonstrated satisfactory corneal ultrastructural preservation. The rapid and modified tissue processing method for preparing the resin-embedded is particularly beneficial to accelerate the microscopic evaluation in ophthalmology and optometry. PMID:22570589

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

PubMed

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

2012-11-01

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

Video-task acquisition in rhesus monkeys (Macaca mulatta) and chimpanzees (Pan troglodytes): a comparative analysis

NASA Technical Reports Server (NTRS)

Hopkins, W. D.; Washburn, D. A.; Hyatt, C. W.; Rumbaugh, D. M. (Principal Investigator)

1996-01-01

This study describes video-task acquisition in two nonhuman primate species. The subjects were seven rhesus monkeys (Macaca mulatta) and seven chimpanzees (Pan troglodytes). All subjects were trained to manipulate a joystick which controlled a cursor displayed on a computer monitor. Two criterion levels were used: one based on conceptual knowledge of the task and one based on motor performance. Chimpanzees and rhesus monkeys attained criterion in a comparable number of trials using a conceptually based criterion. However, using a criterion based on motor performance, chimpanzees reached criterion significantly faster than rhesus monkeys. Analysis of error patterns and latency indicated that the rhesus monkeys had a larger asymmetry in response bias and were significantly slower in responding than the chimpanzees. The results are discussed in terms of the relation between object manipulation skills and video-task acquisition.

Social Tolerance in Wild Female Crested Macaques (Macaca nigra) in Tangkoko-Batuangus Nature Reserve, Sulawesi, Indonesia

PubMed Central

Duboscq, Julie; Micheletta, Jérôme; Agil, Muhammad; Hodges, Keith; Thierry, Bernard; Engelhardt, Antje

2013-01-01

In primates, females typically drive the evolution of the social system and present a wide diversity of social structures. To understand this diversity, it is necessary to document the consistency and/or flexibility of female social structures across and within species, contexts, and environments. Macaques (Macaca sp.) are an ideal taxon for such comparative study, showing both consistency and variation in their social relations. Their social styles, constituting robust sets of social traits, can be classified in four grades, from despotic to tolerant. However, tolerant species are still understudied, especially in the wild. To foster our understanding of tolerant societies and to assess the validity of the concept of social style, we studied female crested macaques, Macaca nigra, under entirely natural conditions. We assessed their degree of social tolerance by analyzing the frequency, intensity, and distribution of agonistic and affiliative behaviors, their dominance gradient, their bared-teeth display, and their level of conciliatory tendency. We also analyzed previously undocumented behavioral patterns in grade 4 macaques: reaction upon approach and distribution of affiliative behavior across partners. We compared the observed patterns to data from other populations of grade 4 macaques and from species of other grades. Overall, female crested macaques expressed a tolerant social style, with low intensity, frequently bidirectional, and reconciled conflicts. Dominance asymmetry was moderate, associated with an affiliative bared-teeth display. Females greatly tolerated one another in close proximity. The observed patterns matched the profile of other tolerant macaques and were outside the range of patterns of more despotic species. This study is the first comprehensive analysis of females’ social behavior in a tolerant macaque species under natural conditions and as such, contributes to a better understanding of macaque societies. It also highlights the

Risk Factors for Dystocia in Pigtailed Macaques (Macaca nemestrina)

PubMed Central

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

2011-01-01

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. PMID:21535929

Contrafreeloading and the value of control over visual stimuli in Japanese macaques (Macaca fuscata).

PubMed

Ogura, Tadatoshi

2011-05-01

Contrafreeloading, which means that animals work for food even though identical food is freely available, has been reported in animals' feeding behavior. This phenomenon has been assumed to be explained by the information primacy model, in which the information about a food resource as well as the food itself is valuable for animals. This study confirmed a contrafreeloading-like phenomenon using movies as rewards rather than food in Japanese macaques (Macaca fuscata) and investigated the motivational system that exists behind contrafreeloading. In the experiment, movies that were presented dependently on subjects' responses (earned movies) and movies that were presented automatically (free movies) were supplied simultaneously. The subjects continued to make responses to obtain the presentation of the earned movies although identical movies were available as free movies. These results provide the first evidence of contrafreeloading that occurs with movie rewards. The motivation maintaining the contrafreeloading behavior for movies may be control over the environment according to the competence theory.

Do rhesus monkeys (Macaca mulatta) perceive illusory motion?

PubMed

Agrillo, Christian; Gori, Simone; Beran, Michael J

2015-07-01

During the last decade, visual illusions have been used repeatedly to understand similarities and differences in visual perception of human and non-human animals. However, nearly all studies have focused only on illusions not related to motion perception, and to date, it is unknown whether non-human primates perceive any kind of motion illusion. In the present study, we investigated whether rhesus monkeys (Macaca mulatta) perceived one of the most popular motion illusions in humans, the Rotating Snake illusion (RSI). To this purpose, we set up four experiments. In Experiment 1, subjects initially were trained to discriminate static versus dynamic arrays. Once reaching the learning criterion, they underwent probe trials in which we presented the RSI and a control stimulus identical in overall configuration with the exception that the order of the luminance sequence was changed in a way that no apparent motion is perceived by humans. The overall performance of monkeys indicated that they spontaneously classified RSI as a dynamic array. Subsequently, we tested adult humans in the same task with the aim of directly comparing the performance of human and non-human primates (Experiment 2). In Experiment 3, we found that monkeys can be successfully trained to discriminate between the RSI and a control stimulus. Experiment 4 showed that a simple change in luminance sequence in the two arrays could not explain the performance reported in Experiment 3. These results suggest that some rhesus monkeys display a human-like perception of this motion illusion, raising the possibility that the neurocognitive systems underlying motion perception may be similar between human and non-human primates.

Postsacral vertebral morphology in relation to tail length among primates and other mammals.

PubMed

Russo, Gabrielle A

2015-02-01

Tail reduction/loss independently evolved in a number of mammalian lineages, including hominoid primates. One prerequisite to appropriately contextualizing its occurrence and understanding its significance is the ability to track evolutionary changes in tail length throughout the fossil record. However, to date, the bony correlates of tail length variation among living taxa have not been comprehensively examined. This study quantifies postsacral vertebral morphology among living primates and other mammals known to differ in relative tail length (RTL). Linear and angular measurements with known biomechanical significance were collected on the first, mid-, and transition proximal postsacral vertebrae, and their relationship with RTL was assessed using phylogenetic generalized least-squares regression methods. Compared to shorter-tailed primates, longer-tailed primates possess a greater number of postsacral vertebral features associated with increased proximal tail flexibility (e.g., craniocaudally longer vertebral bodies), increased intervertebral body joint range of motion (e.g., more circularly shaped cranial articular surfaces), and increased leverage of tail musculature (e.g., longer spinous processes). These observations are corroborated by the comparative mammalian sample, which shows that distantly related short-tailed (e.g., Phascolarctos, Lynx) and long-tailed (e.g., Dendrolagus, Acinonyx) nonprimate mammals morphologically converge with short-tailed (e.g., Macaca tonkeana) and long-tailed (e.g., Macaca fascicularis) primates, respectively. Multivariate models demonstrate that the variables examined account for 70% (all mammals) to 94% (only primates) of the variance in RTL. Results of this study may be used to infer the tail lengths of extinct primates and other mammals, thereby improving our understanding about the evolution of tail reduction/loss. © 2014 Wiley Periodicals, Inc.

Molecular Cytogenetic Analysis of One African and Five Asian Macaque Species Reveals Identical Karyotypes as in Mandrill.

PubMed

Sangpakdee, Wiwat; Tanomtong, Alongkoad; Chaveerach, Arunrat; Pinthong, Krit; Trifonov, Vladimir; Loth, Kristina; Hensel, Christiana; Liehr, Thomas; Weise, Anja; Fan, Xiaobo

2018-04-01

The question how evolution and speciation work is one of the major interests of biology. Especially, genetic including karyotypic evolution within primates is of special interest due to the close phylogenetic position of Macaca and Homo sapiens and the role as in vivo models in medical research, neuroscience, behavior, pharmacology, reproduction and Acquired Immune Deficiency Syndrome (AIDS). Karyotypes of five macaque species from South East Asia and of one macaque species as well as mandrill from Africa were analyzed by high resolution molecular cytogenetics to obtain new insights into karyotypic evolution of old world monkeys. Molecular cytogenetics applying human probes and probe sets was applied in chromosomes of Macaca arctoides, M. fascicularis, M. nemestrina, M. assamensis, M. sylvanus, M. mulatta and Mandrillus sphinx. Established two- to multicolor-fluorescence in situ hybridization (FISH) approaches were applied. Locus-specific probes, whole and partial chromosome paint probes were hybridized. Especially the FISH-banding approach multicolor-banding (MCB) as well as probes oriented towards heterochromatin turned out to be highly efficient for interspecies comparison. Karyotypes of all seven studied species could be characterized in detail. Surprisingly, no evolutionary conserved differences were found among macaques, including mandrill. Between the seven here studied and phenotypically so different species we expected several via FISH detectable karyoypic and submicroscopic changes and were surprised to find none of them on a molecular cytogenetic level. Spatial separation, may explain the speciation and different evolution for some of them, like African M. sylvanus, Mandrillus sphinx and the South Asian macaques. However, for the partially or completely overlapping habitats of the five studied South Asian macaques the species separation process can also not be deduced to karyotypic separation.

Non-invasive surveillance for Plasmodium in reservoir macaque species.

PubMed

Siregar, Josephine E; Faust, Christina L; Murdiyarso, Lydia S; Rosmanah, Lis; Saepuloh, Uus; Dobson, Andrew P; Iskandriati, Diah

2015-10-12

Primates are important reservoirs for human diseases, but their infection status and disease dynamics are difficult to track in the wild. Within the last decade, a macaque malaria, Plasmodium knowlesi, has caused disease in hundreds of humans in Southeast Asia. In order to track cases and understand zoonotic risk, it is imperative to be able to quantify infection status in reservoir macaque species. In this study, protocols for the collection of non-invasive samples and isolation of malaria parasites from naturally infected macaques are optimized. Paired faecal and blood samples from 60 Macaca fascicularis and four Macaca nemestrina were collected. All animals came from Sumatra or Java and were housed in semi-captive breeding colonies around West Java. DNA was extracted from samples using a modified protocol. Nested polymerase chain reactions (PCR) were run to detect Plasmodium using primers targeting mitochondrial DNA. Sensitivity of screening faecal samples for Plasmodium was compared to other studies using Kruskal Wallis tests and logistic regression models. The best primer set was 96.7 % (95 % confidence intervals (CI): 83.3-99.4 %) sensitive for detecting Plasmodium in faecal samples of naturally infected macaques (n = 30). This is the first study to produce definitive estimates of Plasmodium sensitivity and specificity in faecal samples from naturally infected hosts. The sensitivity was significantly higher than some other studies involving wild primates. Faecal samples can be used for detection of malaria infection in field surveys of macaques, even when there are no parasites visible in thin blood smears. Repeating samples from individuals will improve inferences of the epidemiology of malaria in wild primates.

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’

PubMed Central

Glaze, Elizabeth R; Roy, Michael J; Dalrymple, Lonnie W; Lanning, Lynda L

2015-01-01

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). PMID:26141449

The effects of thermal and high-CO2 stresses on the metabolism and surrounding microenvironment of the coral Galaxea fascicularis.

PubMed

Agostini, Sylvain; Fujimura, Hiroyuki; Higuchi, Tomihiko; Yuyama, Ikuko; Casareto, Beatriz E; Suzuki, Yoshimi; Nakano, Yoshikatsu

2013-08-01

The effects of elevated temperature and high pCO2 on the metabolism of Galaxea fascicularis were studied with oxygen and pH microsensors. Photosynthesis and respiration rates were evaluated from the oxygen fluxes from and to the coral polyps. High-temperature alone lowered both photosynthetic and respiration rates. High pCO2 alone did not significantly affect either photosynthesis or respiration rates. Under a combination of high-temperature and high-CO2, the photosynthetic rate increased to values close to those of the controls. The same pH in the diffusion boundary layer was observed under light in both (400 and 750 ppm) CO2 treatments, but decreased significantly in the dark as a result of increased CO2. The ATP contents decreased with increasing temperature. The effects of temperature on the metabolism of corals were stronger than the effects of increased CO2. The effects of acidification were minimal without combined temperature stress. However, acidification combined with higher temperature may affect coral metabolism due to the amplification of diel variations in the microenvironment surrounding the coral and the decrease in ATP contents. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

An experimental investigation of referential looking in free-ranging Barbary macaques (Macaca sylvanus).

PubMed

Roberts, Sam G B; McComb, Karen; Ruffman, Ted

2008-02-01

The authors examined looking behavior between 15 Barbary macaque (Macaca sylvanus) infants and their mothers in the presence of a rubber snake (experimental period) and in the absence of the snake (control period). Two of the 15 infants looked referentially at their mother in the experimental period. Including both referential and nonreferential looks, the six older infants (aged 5 to 12 months) displayed a higher frequency of looks to mother than nine younger infants (aged 3 to 4.5 months) in the experimental period, but not in the control period. Older infants looked more to the mother in the experimental condition, whereas the younger infants looked more to the mother in the control condition, or looked equally in the two conditions. These results suggest that age is an important factor in determining looking behavior to mother in situations of uncertainty. Compared to hand-reared chimpanzees or human infants tested in standard social referencing paradigms, the infant macaques displayed a low rate of referential looking. Possible explanations for this are discussed. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

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

PubMed

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.

The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

PubMed

Lim, Khai Lone; Amir, Amirah; Lau, Yee Ling; Fong, Mun Yik

2017-08-11

The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated. The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes. Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P < 0.0001). However, no difference in binding activity level was seen in the binding assay using M. fascicularis erythrocytes. This study is the first report of phenotypic difference between PkDBPαII haplotypes. The biological implication of this finding is yet to be determined. Therefore, further studies need to be carried out to determine whether this differential binding level can be associated with severity of knowlesi malaria in human.

Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal.

PubMed

Kyes, Randall C; Jones-Engel, Lisa; Chalise, Mukesh K; Engel, Gregory; Heidrich, John; Grant, Richard; Bajimaya, Shyam S; McDonough, John; Smith, David Glenn; Ferguson, Betsy

2006-05-01

Indian-origin rhesus macaques (Macaca mulatta) have long served as an animal model for the study of human disease and behavior. Given the current shortage of Indian-origin rhesus, many researchers have turned to rhesus macaques from China as a substitute. However, a number of studies have identified marked genetic differences between the Chinese and Indian animals. We investigated the genetic characteristics of a third rhesus population, the rhesus macaques of Nepal. Twenty-one rhesus macaques at the Swoyambhu Temple in Kathmandu, Nepal, were compared with more than 300 Indian- and Chinese-origin rhesus macaques. The sequence analyses of two mitochondrial DNA (mtDNA) loci, from the HVS I and 12 S rRNA regions, showed that the Nepali animals were more similar to Indian-origin than to Chinese-origin animals. The distribution of alleles at 24 short tandem repeat (STR) loci distributed across 17 chromosomes also showed greater similarity between the Nepali and Indian-origin animals. Finally, an analysis of seven major histocompatibility complex (MHC) alleles showed that the Nepali animals expressed Class I alleles that are common to Indian-origin animals, including Mamu-A*01. All of these analyses also revealed a low level of genetic diversity within this Nepali rhesus sample. We conclude that the rhesus macaques of Nepal more closely resemble rhesus macaques of Indian origin than those of Chinese origin. As such, the Nepali rhesus may offer an additional resource option for researchers who wish to maintain research protocols with animals that possess key genetic features characteristic of Indian-origin rhesus macaques. 2005 Wiley-Liss, Inc.

Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand.

PubMed

Nakgoi, Khajornpong; Nitatpattana, Narong; Wajjwalku, Worawidh; Pongsopawijit, Pornsawan; Kaewchot, Supakarn; Yoksan, Sutee; Siripolwat, Voravit; Souris, Marc; Gonzalez, Jean-Paul

2014-01-01

The potential of macaque Macaca nemestrina leonina in Thailand to be infected by endemic arboviruses was assessed. The prevalence of antibodies of three arboviruses actively circulating in Thailand was determined by Plaque Reduction Neutralization assay procedures using samples from captive colonies in Northern Thailand. Out of 38 macaques, 9 (24%) presented reacting antibodies against dengue virus, 5 (13%) against Japanese encephalitis virus, and 4 (10%) against Chikungunya virus. Our results indicate that the northern pig-tailed macaque in Thailand can be infected by these arboviruses, inferring therefore that their virus specific vectors have bitten them. Given that, northern pig-tailed macaque represents an abundant population, living in close range to human or in peridomestic setting, they could play a role as potential reservoir host for arboviruses circulating in Thailand. © 2013 Wiley Periodicals, Inc.

Investigation of cadmium contamination using hair of the Japanese macaque, Macaca fuscata, from Shimokita Peninsula, Aomori Prefecture in Japan.

PubMed

Mochizuki, Mariko; Anahara, Reiko; Mano, Tomoki; Nakayama, Yuri; Kobori, Mutsumi; Omi, Toshinori; Matsuoka, Shiro; Ueda, Fukiko

2012-09-01

The cadmium (Cd) contents in hair of macaques (n = 45, Macaca fuscata) living on the Shimokita Peninsula were investigated. The mean Cd contents in the hair of Japanese (n = 34, 5.01 μg/g) and macaques (3.05 μg/g) tendency to be higher than those of animals living other areas. The Cd contents of hair of wild macaques were significantly (p < 0.01) lower than that of humans, although three were no significant difference between Cd contents of humans and that of the macaque in captivity. The hair of the macaque was suggested as a useful sample for measurement of Cd contamination in the environment.

Computed tomography or necropsy diagnosis of multiple bullae and the treatment of pneumothorax in rhesus macaques (Macaca mulatta).

PubMed

Kim, Jong-Min; Han, Sungyoung; Shin, Jun-Seop; Min, Byoung-Hoon; Jeong, Won Young; Lee, Ga Eul; Kim, Min Sun; Kim, Ju Eun; Chung, Hyunwoo; Park, Chung-Gyu

2017-10-01

Pulmonary bullae and pneumothorax have various etiologies in veterinary medicine. We diagnosed multiple pulmonary bullae combined with or without pneumothorax by computed tomography (CT) or necropsy in seven rhesus macaques (Macaca mulatta) imported from China. Two of seven rhesus macaques accompanied by pneumothorax were cured by fixation of ruptured lung through left or right 3rd intercostal thoracotomy. Pneumonyssus simicola, one of the etiologies of pulmonary bullae, was not detected from tracheobronchiolar lavage. To the best of our knowledge, this is the first case report on the CT-aided diagnosis of pulmonary bullae and the successful treatment of combined pneumothorax by thoracotomy in non-human primates (NHPs). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evidence of Placentophagia and Mother-Infant Cannibalism in Free-Ranging Macaca mulatta tcheliensis in Mount Taihangshan, Jiyuan, China.

PubMed

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.

Antagonism of the Ethanol-Like Discriminative Stimulus Effects of Ethanol, Pentobarbital, and Midazolam in Cynomolgus Monkeys Reveals Involvement of Specific GABAA Receptor SubtypesS⃞

PubMed Central

Rogers, Laura S. M.; Grant, Kathleen A.

2009-01-01

The γ-aminobutyric acid (GABA)A receptors mediating the discriminative stimulus effects of ethanol were studied by comparing the potency of ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)benzodiazepine-3-carboxylate (Ro15-4513) and ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)-benzodiazepine-3-carboxylate (flumazenil, Ro15-1788) to antagonize ethanol, pentobarbital (PB), and midazolam substitution for ethanol. Ro15-4513 has high affinity for receptors containing α4/6 and α5 subunits and lower affinity for α1, α2, and α3 subunits. Flumazenil is nonselective for GABAA receptors containing α1, α2, α3, and α5 subunits and has low affinity for α4/6-containing receptors. Male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) were trained to discriminate ethanol (1.0 or 2.0 g/kg i.g., 30-min pretreatment) from water. Ethanol, PB, and midazolam dose-dependently substituted for ethanol (80% ethanol-appropriate responding). Ro15-4513 (0.003–0.56 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in a vast majority of monkeys tested (15/15, 16/17, and 11/12, respectively). In contrast, flumazenil (0.30–10.0 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in 9 of 16, 12 of 16, and 7 of 9 monkeys tested, respectively. In the monkeys showing antagonism with both Ro15-4513 and flumazenil, ethanol and PB substitution were antagonized more potently by Ro15-4513 than by flumazenil, whereas midazolam substitution was antagonized with similar potency. There were no sex or training dose differences, with the exception that flumazenil failed to antagonize ethanol substitution in males trained to discriminate 2.0 g/kg ethanol. GABAA receptors with high affinity for Ro15-4513 (i.e., containing α4/6 and α5 subunits) may be particularly important mediators of the multiple discriminative stimulus effects of ethanol

A structural comparison of female-male and female-female mounting in Japanese macaques (Macaca fuscata).

PubMed

Ottenheimer Carrier, Lydia; Leca, Jean-Baptiste; Pellis, Sergio; Vasey, Paul L

2015-10-01

In certain populations, female Japanese macaques (Macaca fuscata) mount both males and females. Vasey (2007) proposed that female-female sexual mounting in Japanese macaques may be a neutral evolutionary by-product of a purported adaptation, namely, female-male mounting. In this study, we aim to further examine the proposed link between female-male and female-female mounting in Japanese macaques by comparing the structural characteristics that define both forms of mounting. We do so using Eshkol-Wachman Movement Notation (EWMN), a globographic reference system that can be used to describe the position of body segments. No significant differences were observed in the female mounters' positioning of eight different body segments (i.e., lower torso, mid-torso, upper torso, upper arm, lower arm, upper leg, lower leg, and foot) during female-male and female-female mounting. This finding lends support to the conclusion that female-female and female-male mounting are structurally, and thus, evolutionarily, related. Copyright © 2015 Elsevier B.V. All rights reserved.

A Chinese rhesus macaque (Macaca mulatta) model for vaginal Lactobacillus colonization and live microbicide development

PubMed Central

Yu, Rosa R.; Cheng, Andrew T.; Lagenaur, Laurel A.; Huang, Wenjun; Weiss, Deborah E.; Treece, Jim; Sanders-Beer, Brigitte E.; Hamer, Dean H.; Lee, Peter P.; Xu, Qiang; Liu, Yang

2015-01-01

Background We sought to establish a nonhuman primate model of vaginal Lactobacillus colonization suitable for evaluating live microbial microbicide candidates. Methods Vaginal and rectal microflora in Chinese rhesus macaques (Macaca mulatta) were analyzed, with cultivable bacteria identified by 16S rRNA gene sequencing. Live lactobacilli were intravaginally administered to evaluate bacterial colonization. Results Chinese rhesus macaques harbored abundant vaginal Lactobacillus, with Lactobacillus johnsonii as the predominant species. Like humans, most examined macaques harbored only one vaginal Lactobacillus species. Vaginal and rectal Lactobacillus isolates from the same animal exhibited different genetic and biochemical profiles. Vaginal Lactobacillus was cleared by a vaginal suppository of azithromycin, and endogenous L. johnsonii was subsequently restored by intravaginal inoculation. Importantly, prolonged colonization of a human vaginal Lactobacillus jensenii was established in these animals. Conclusions The Chinese rhesus macaque harbors vaginal Lactobacillus and is a potentially useful model to support the pre-clinical evaluation of Lactobacillus-based topical microbicides. PMID:19367737

Redescription of Enterobius (Enterobius) macaci Yen, 1973 (Nematoda: Oxyuridae: Enterobiinae) based on material collected from wild Japanese macaque, Macaca fuscata (Primates: Cercopithecidae).

PubMed

Hasegawa, Hideo; Sato, Hiroshi; Torii, Harumi

2012-02-01

Enterobius (Enterobius) macaci Yen, 1973 (Nematoda: Oxyuridae: Enterobiinae) was collected from a Japanese macaque, Macaca fuscata, in Nara and Yamaguchi Prefectures, Honshu Island, Japan, for the first time. A redescription is presented along with DNA sequence data. This pinworm is a typical member of the subgenus Enterobius and is characteristic in the spicule morphology, being readily distinguished from other congeners. Phylogenetic analyses based on 18S ribosomal RNA gene (rDNA) and mitochondrial DNA (mtDNA) Cox1 gene assign its position in the pinworm lineage adapted to the Old World primates, showing divergence before the splitting of the chimpanzee and human pinworms.

Outbreak of larval Echinococcus multilocularis infection in Japanese monkey (Macaca fuscata) in a zoo, Hokkaido: western blotting patterns in the infected monkeys.

PubMed

Sato, Chiaki; Kawase, Shiro; Yano, Shoki; Nagano, Hideki; Fujimoto, Satoshi; Kobayashi, Nobuyuki; Miyahara, Kazuro; Yamada, Kazutaka; Sato, Motoyoshi; Kobayashi, Yoshiyasu

2005-01-01

A high prevalence of larval Echinococcus multilocularis (Em) infection was found in zoo primates in Hokkaido, Japan. In October 1997, a Japanese monkey (Macaca fuscata) died and histopathologically diagnosed as alveolar hydatidosis. Serum samples were collected from the remaining Japanese monkeys and examined for antibodies against Em by enzyme-linked immunosorbent assay and western blotting. Serological tests showed 12 more animals of the remaining 57 monkeys were possibly infected. Ultrasonography revealed that nine of these 12 animals had a cystic lesion in the liver. The band patterns of western blotting in the monkeys were very similar to those in human.

Social bonds affect anti-predator behaviour in a tolerant species of macaque, Macaca nigra.

PubMed

Micheletta, Jérôme; Waller, Bridget M; Panggur, Maria R; Neumann, Christof; Duboscq, Julie; Agil, Muhammad; Engelhardt, Antje

2012-10-07

Enduring positive social bonds between individuals are crucial for humans' health and well being. Similar bonds can be found in a wide range of taxa, revealing the evolutionary origins of humans' social bonds. Evidence suggests that these strong social bonds can function to buffer the negative effects of living in groups, but it is not known whether they also function to minimize predation risk. Here, we show that crested macaques (Macaca nigra) react more strongly to playbacks of recruitment alarm calls (i.e. calls signalling the presence of a predator and eliciting cooperative mobbing behaviour) if they were produced by an individual with whom they share a strong social bond. Dominance relationships between caller and listener had no effect on the reaction of the listener. Thus, strong social bonds may improve the coordination and efficiency of cooperative defence against predators, and therefore increase chances of survival. This result broadens our understanding of the evolution and function of social bonds by highlighting their importance in the anti-predator context.

Social bonds affect anti-predator behaviour in a tolerant species of macaque, Macaca nigra

PubMed Central

Micheletta, Jérôme; Waller, Bridget M.; Panggur, Maria R.; Neumann, Christof; Duboscq, Julie; Agil, Muhammad; Engelhardt, Antje

2012-01-01

Enduring positive social bonds between individuals are crucial for humans' health and well being. Similar bonds can be found in a wide range of taxa, revealing the evolutionary origins of humans' social bonds. Evidence suggests that these strong social bonds can function to buffer the negative effects of living in groups, but it is not known whether they also function to minimize predation risk. Here, we show that crested macaques (Macaca nigra) react more strongly to playbacks of recruitment alarm calls (i.e. calls signalling the presence of a predator and eliciting cooperative mobbing behaviour) if they were produced by an individual with whom they share a strong social bond. Dominance relationships between caller and listener had no effect on the reaction of the listener. Thus, strong social bonds may improve the coordination and efficiency of cooperative defence against predators, and therefore increase chances of survival. This result broadens our understanding of the evolution and function of social bonds by highlighting their importance in the anti-predator context. PMID:22859593

Role of vocal tract characteristics in individual discrimination by Japanese macaques (Macaca fuscata).

PubMed

Furuyama, Takafumi; Kobayasi, Kohta I; Riquimaroux, Hiroshi

2016-08-23

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.

Prenatal growth of the interorbital septum in Macaca mulatta.

PubMed

Lozanoff, Scott; Doll, Sara; Hallgrimsson, Benedikt; Neufeld, Eric

2004-12-01

The interorbital septum is the portion of the anterior cranial base directly contiguous with the eyes. It is considered to be a primitive trait that has evolved independently in various primate groups as a result of ocular and olfactory convergence with concomitant encephalization. This process is hypothesized to have reduced the size of the lateral nasal capsule exposing the anterior cranial base to the ocular apparatus and thus creating an interorbital septum. The purpose of this study was to determine whether differential growth trajectories occur among the chondrocranial elements corresponding to this hypothesis. Macaca mulatta embryos from the Zingeser Collection were selected for this analysis since this primate shows a well-developed interorbital septum throughout ontogeny. Embryos between 40 and 90 days of gestation were selected from the collection and coronal sections including the eye, anterior cranial base and lateral nasal capsule were subjected to video microscopy and computerized reconstruction using SURFdriver Software. Tissue volumes were computed for these tissues while chondrocytic growth attributes were measured utilizing stereological techniques. Results showed a strong correlation between the volume of the lateral nasal capsule and anterior cranial base and these two structures showed a consistent correlation with an increasing eye volume. Chondrocytic volume density and average diameter were larger in the lateral nasal capsule while shape, numerical density and average volume did not differ between the two tissues. These data suggest if differential growth does account for a reduction of the nasal capsule compared to the central cranial base stem, it does not appear to result from differential tissue size change. However, certain cellular growth activities leading to premature chondrocytic hypertrophy may be involved.

Habitual hot-spring bathing by a group of Japanese macaques (Macaca fuscata) in their natural habitat.

PubMed

Zhang, Peng; Watanabe, Kunio; Eishi, Tokida

2007-12-01

Japanese macaques (Macaca fuscata) in a free-ranging group in Jigokudani valley, Nagano prefecture, are known to bathe in a hot spring. We used scan sampling in a study aimed at elucidating the causal factors and possible social transmission of this behavior. From 1980-2003, 31% of a total 114 females in the group habitually bathed in the hot spring. The habit was more widespread in dominant matrilines than in subordinate matrilines. Infants whose mothers bathed were more likely to bathe than infants of mothers who did not bathe. The number of monkeys bathing was clearly influenced by ambient air temperature. More monkeys bathed in the hot spring in winter than in summer. The results support the thermoregulation hypothesis of hot-spring bathing. Bathing behavior varies among age and sex categories of monkeys, with adult females and juveniles bathing more often than adult males and subadults. We compared hot-spring bathing with other thermoregulatory behaviors in various primate populations. (c) 2007 Wiley-Liss, Inc.

Serum biomarkers of Burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses.

PubMed

Glaros, Trevor G; Blancett, Candace D; Bell, Todd M; Natesan, Mohan; Ulrich, Robert G

2015-01-01

The bacterium Burkholderia mallei is the etiological agent of glanders, a highly contagious, often fatal zoonotic infectious disease that is also a biodefense concern. Clinical laboratory assays that analyze blood or other biological fluids are the highest priority because these specimens can be collected with minimal risk to the patient. However, progress in developing sensitive assays for monitoring B. mallei infection is hampered by a shortage of useful biomarkers. Reasoning that there should be a strong correlation between the proteomes of infected tissues and circulating serum, we employed imaging mass spectrometry (IMS) of thin-sectioned tissues from Chlorocebus aethiops (African green) monkeys infected with B. mallei to localize host and pathogen proteins that were associated with abscesses. Using laser-capture microdissection of specific regions identified by IMS and histology within the tissue sections, a more extensive proteomic analysis was performed by a technique that combined the physical separation capabilities of liquid chromatography (LC) with the sensitive mass analysis capabilities of mass spectrometry (LC-MS/MS). By examining standard formalin-fixed, paraffin-embedded tissue sections, this strategy resulted in the identification of several proteins that were associated with lung and skin abscesses, including the host protein calprotectin and the pathogen protein GroEL. Elevated levels of calprotectin detected by ELISA and antibody responses to GroEL, measured by a microarray of the bacterial proteome, were subsequently detected in the sera of C. aethiops, Macaca mulatta, and Macaca fascicularis primates infected with B. mallei. Our results demonstrate that a combination of multidimensional MS analysis of traditional histology specimens with high-content protein microarrays can be used to discover lead pairs of host-pathogen biomarkers of infection that are identifiable in biological fluids.

Compositionality in neural control: an interdisciplinary study of scribbling movements in primates

PubMed Central

Abeles, Moshe; Diesmann, Markus; Flash, Tamar; Geisel, Theo; Herrmann, Michael; Teicher, Mina

2013-01-01

This article discusses the compositional structure of hand movements by analyzing and modeling neural and behavioral data obtained from experiments where a monkey (Macaca fascicularis) performed scribbling movements induced by a search task. Using geometrically based approaches to movement segmentation, it is shown that the hand trajectories are composed of elementary segments that are primarily parabolic in shape. The segments could be categorized into a small number of classes on the basis of decreasing intra-class variance over the course of training. A separate classification of the neural data employing a hidden Markov model showed a coincidence of the neural states with the behavioral categories. An additional analysis of both types of data by a data mining method provided evidence that the neural activity patterns underlying the behavioral primitives were formed by sets of specific and precise spike patterns. A geometric description of the movement trajectories, together with precise neural timing data indicates a compositional variant of a realistic synfire chain model. This model reproduces the typical shapes and temporal properties of the trajectories; hence the structure and composition of the primitives may reflect meaningful behavior. PMID:24062679

A preliminary study on activity budget, daily travel distance and feeding behaviour of long-tailed macaques and spectacled dusky leaf monkey in Bangi campus of Universiti Kebangsaan Malaysia, Selangor

NASA Astrophysics Data System (ADS)

Ruslin, Farhani; Yaakop, Salmah; Zain, Badrul Munir Md.

2014-09-01

The activity budget, ranging behaviour and feeding behaviour of a multimale-multifemale group of long-tailed macaques (Macaca fascicularis) and a multimale-multifemale group of spectacled dusky leaf monkey (Trachypithecus obscurus) were studied. A total of 145 hours and 143 hours have been spent to observe the group of long-tailed macaque and spectacled dusky leaf monkey that ranged the same habitat adjacent to the campus areas. The researchers examined the activity budgets, daily travel length and feeding activity of both species and distinguished how the sympatric species used the same forested habitat. Preliminary study found that the long-tailed macaques spent longer time feeding, moving than resting and other activities. On the other hand, the dusky leaf monkey spent much time in feeding and resting than moving. The differences of daily pattern between these two groups are significant. Macaques have higher daily mean of path length compared to the dusky leaf monkey and spent much time moving compare to the leaf monkey group. The spectacled dusky leaf monkey group also has fully utilized the forested areas where else the long-tailed macaques adopted foraging to the adjacent residential colleges.

Transplantation of iPS-Derived Tumor Cells with a Homozygous MHC Haplotype Induces GRP94 Antibody Production in MHC-Matched Macaques.

PubMed

Ishigaki, Hirohito; Maeda, Toshinaga; Inoue, Hirokazu; Akagi, Tsuyoshi; Sasamura, Takako; Ishida, Hideaki; Inubushi, Toshiro; Okahara, Junko; Shiina, Takashi; Nakayama, Misako; Itoh, Yasushi; Ogasawara, Kazumasa

2017-11-01

Immune surveillance is a critical component of the antitumor response in vivo , yet the specific components of the immune system involved in this regulatory response remain unclear. In this study, we demonstrate that autoantibodies can mitigate tumor growth in vitro and in vivo We generated two cancer cell lines, embryonal carcinoma and glioblastoma cell lines, from monkey-induced pluripotent stem cells (iPSC) carrying a homozygous haplotype of major histocompatibility complex (MHC, Mafa in Macaca fascicularis). To establish a monkey cancer model, we transplanted these cells into monkeys carrying the matched Mafa haplotype in one of the chromosomes. Neither Mafa-homozygous cancer cell line grew in monkeys carrying the matched Mafa haplotype heterozygously. We detected in the plasma of these monkeys an IgG autoantibody against GRP94, a heat shock protein. Injection of the plasma prevented growth of the tumor cells in immunodeficient mice, whereas plasma IgG depleted of GRP94 IgG exhibited reduced killing activity against cancer cells in vitro These results indicate that humoral immunity, including autoantibodies against GRP94, plays a role in cancer immune surveillance. Cancer Res; 77(21); 6001-10. ©2017 AACR . ©2017 American Association for Cancer Research.

Human behavior and opportunities for parasite transmission in communities surrounding long-tailed macaque populations in Bali, Indonesia.

PubMed

Lane-DeGraaf, Kelly E; Putra, I G A Arta; Wandia, I Nengah; Rompis, Aida; Hollocher, Hope; Fuentes, Agustin

2014-02-01

Spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (Macaca fascicularis), concentrating them in areas in close proximity to humans. In this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestinal parasites to understand if age, education level, or occupation are significant determinants of exposure behaviors. These exposure risk behaviors and attitudes include fear of macaques, direct contact with macaques, owning pet macaques, hunting and eating macaques, and overlapping water uses. We find that willingness to participate in exposure risk behaviors are correlated with an individual's occupation, age, and/or education level. We also found that because the actual risk of infection varies across populations, activities such as direct macaque contact and pet ownership, could be putting individuals at real risk in certain contexts. Thus, we show that human demographics and social structure can influence willingness to participate in behaviors putting them at increased risk for exposure to parasites. © 2013 Wiley Periodicals, Inc.

Multiple adaptable mechanisms early in the primate visual pathway

PubMed Central

Dhruv, Neel T.; Tailby, Chris; Sokol, Sach H.; Lennie, Peter

2011-01-01

We describe experiments that isolate and characterize multiple adaptable mechanisms that influence responses of orientation-selective neurons in primary visual cortex (V1) of anesthetized macaque (Macaca fascicularis). The results suggest that three adaptable stages of machinery shape neural responses in V1: a broadly-tuned early stage and a spatio-temporally tuned later stage, both of which provide excitatory input, and a normalization pool that is also broadly tuned. The early stage and the normalization pool are revealed by adapting gratings that themselves fail to evoke a response from the neuron: either low temporal frequency gratings at the null orientation or gratings of any orientation drifting at high temporal frequencies. When effective, adapting stimuli that altered the sensitivity of these two mechanisms caused reductions of contrast gain and often brought about a paradoxical increase in response gain due to a relatively greater desensitization of the normalization pool. The tuned mechanism is desensitized only by stimuli well-matched to a neuron’s receptive field. We could thus infer desensitization of the tuned mechanism by comparing effects obtained with adapting gratings of preferred and null orientation modulated at low temporal frequencies. PMID:22016535

Possible shift in macaque trophic level following a century of biodiversity loss in Singapore.

PubMed

Gibson, Luke

2011-07-01

Biodiversity loss in tropical forests is a major problem in conservation biology, and nowhere is this more dire than in Southeast Asia. Deforestation and the associated loss of species may trigger shifts in habitat and feeding preferences of persisting species. In this study, I compared the habitat use and diet of long-tailed macaque (Macaca fascicularis) populations in Singapore from two time periods: museum specimens originally collected between 1893 and 1944, and living macaques sampled in 2009. I collected hair and used stable carbon and nitrogen isotope analysis to identify temporal changes in dietary source and trophic position, respectively. δ(13)C ratios were virtually identical, suggesting that macaques foraged in similar habitats during both time periods. However, δ(15)N ratios decreased considerably over time, suggesting that macaques today feed at a lower trophic level than previously. This decline in trophic level may be because of the disappearance or decline of other species that compete with macaques for fruit. This study highlights the effect of biodiversity loss on persisting species in degraded habitats of Southeast Asia, and improves our understanding of how species will adapt to further human-driven changes in tropical forest habitats.

Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm viruslike particles.

PubMed Central

Bradley, D W; Krawczynski, K; Cook, E H; McCaustland, K A; Humphrey, C D; Spelbring, J E; Myint, H; Maynard, J E

1987-01-01

An experimental model of enterically transmitted non-A, non-B hepatitis (ET-NANBH) was established in tamarins (Saguinus mystax mystax) and cynomolgus macaques (Macaca fascicularis). First-passage animals were inoculated with two different stool suspensions obtained from human patients with well-defined ET-NANBH that originated from Burma and Pakistan, where epidemics of ET-NANBH occur. Both inocula contained 27- ato 34-nm-diameter viruslike particles (VLPs) that were specifically aggregated by acute-phase ET-NANBH sera. ET-NANBH was subpassaged in both tamarins and cynomolgus macaques by using pools of stool suspensions from first-passage animals. One additional passage of disease in cynomolgus macaques resulted in a significantly shortened incubation period and increased severity of disease. VLPs similar to those found in the human inocula were observed in stool specimens of first-, second-, and third-passage cynomolgus macaques and in first- and second-passage tamarins. Our findings indicate that cynomolgus macaques are particularly suitable experimental models for studies of human ET-NANBH. The 27- to 34-nm VLPs found in infected human and primate stools appear to be etiologically linked to disease. Images PMID:3114746

Occupational transmission of an Orthopoxvirus infection during an outbreak in a colony of Macaca tonkeana in Lazio Region, Italy, 2015.

PubMed

Puro, V; Fusco, F M; Castilletti, C; Carletti, F; Colavita, F; Agrati, C; Di Caro, A; Capobianchi, M R; Ippolito, G

2018-03-07

Orthopoxviruses spill over from animal reservoirs to accidental hosts, sometimes causing human infections. We describe the surveillance and infection control measures undertaken during an outbreak due to an Orthopoxvirus occurred in January 2015 in a colony of Macaca tonkeana in the province of Rieti, Latio, Italy, which caused a human asymptomatic infection. According to the epidemiological investigation, the human transmission occurred after an unprotected exposure. The contacts among wild, captive and domestic animals and humans, together with decreased immunity against Orthopoxviruses in the community, may put animal handlers at risk of infection, especially after the cessation of smallpox vaccination. To reduce these threats, standard precautions including respiratory hygiene and transmission-based precautions should be carefully applied also in veterinary medicine. © 2018 Blackwell Verlag GmbH.

Evidence for kind representations in the absence of language: experiments with rhesus monkeys (Macaca mulatta).

PubMed

Phillips, Webb; Santos, Laurie R

2007-03-01

How do we come to recognize and represent different kinds of objects in the world? Some developmental psychologists have hypothesized that learning language plays a crucial role in this capacity. If this hypothesis were correct, then non-linguistic animals should lack the capacity to represent objects as kinds. Previous research with rhesus monkeys (Macaca mulatta) has shown that this species can successfully individuate different kinds of objects - monkeys who saw one kind of object hidden inside a box searched longer after finding a different kind of object. However, in these studies and the infant studies on which they were based, the objects to be individuated differed both in kind and in properties. Thus, subjects in these experiments may not be representing the kinds of objects per se, but instead only their immediate perceptual properties. Here, we show that rhesus monkeys successfully individuate different kinds of objects even when their perceptual properties are held constant. Although these data provide the best evidence to date that language is not necessary to represent kinds, we discuss our findings in terms of possible associative hypotheses as well.

Aggression in pigtailed macaque (Macaca nemestrina) breeding groups affects pregnancy outcome

PubMed Central

Ha, James; Alloway, Hayley; Sussman, Adrienne

2011-01-01

Past research has shown that aggressive behaviors can affect female reproductive outcome in non-human primate captive breeding programs. In this study, aggressive behaviors were recorded in a colony of pigtailed macaque monkeys (Macaca nemestrina) and related to pregnancy outcome. For twenty-two weeks, behavioral data were collected from nine breeding groups, consisting of zero to one male (some males were removed after a cycle of conceptions for husbandry reasons) and four to eight females. Observations included all occurrences of eleven aggressive behaviors during 15-minute observation sessions, one to three times a week. Mean weekly aggression levels during the study period were determined for each group, as well as for each pregnancy. Aggression data were summarized with Principal Components Analyses (PCA). Results indicate that pigtailed macaque aggression falls into five distinctive categories: warn, engage, threaten, pursue, and attack. Breeding groups differed in their levels of aggression, even after controlling for group size, presence of a sire, and group stability. Levels of the five aggression categories were found to affect the probability that a pregnancy ended in either a natural birth of a live infant, a clinical intervention producing a live infant, or a nonviable outcome. The predictive value of aggression was significant when clinical interventions were included as possible reproductive outcomes, Behavioral observation of captive groups could identify “risk” conditions affecting pregnancy outcome and the requirement for clinical intervention. PMID:21898511

Concealing of facial expressions by a wild Barbary macaque (Macaca sylvanus).

PubMed

Thunström, Maria; Kuchenbuch, Paul; Young, Christopher

2014-07-01

Behavioural research on non-vocal communication among non-human primates and its possible links to the origin of human language is a long-standing research topic. Because human language is under voluntary control, it is of interest whether this is also true for any communicative signals of other species. It has been argued that the behaviour of hiding a facial expression with one's hand supports the idea that gestures might be under more voluntary control than facial expressions among non-human primates, and it has also been interpreted as a sign of intentionality. So far, the behaviour has only been reported twice, for single gorilla and chimpanzee individuals, both in captivity. Here, we report the first observation of concealing of facial expressions by a monkey, a Barbary macaque (Macaca sylvanus), living in the wild. On eight separate occasions between 2009 and 2011 an adult male was filmed concealing two different facial expressions associated with play and aggression ("play face" and "scream face"), 22 times in total. The videos were analysed in detail, including gaze direction, hand usage, duration, and individuals present. This male was the only individual in his group to manifest this behaviour, which always occurred in the presence of a dominant male. Several possible interpretations of the function of the behaviour are discussed. The observations in this study indicate that the gestural communication and cognitive abilities of monkeys warrant more research attention.

Parameter comparison of white matter diffusion tensor imaging (DTI) in rhesus macaques (Macaca mulatta)

PubMed Central

MO, Yin; CHAO, Fang; SONG, Ming; LIU, Ci-Rong; LIU, Hui-Lang; QIAN, Xi-Ying; ZHAO, Xu-Dong

2014-01-01

In this study, we analyzed diffusion tensor imaging (DTI) results of brain white matter in rhesus macaques (Macaca mulatta) with four different parameter settings and found that the sequence A (b=1 000 s/mm2, spatial resolution=1.25 mm×1.25 mm× 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm2, spatial resolution=1.25 mm×1.25 mm×1.25 mm, numbers of direction=33, NSA=3) could accurately track coarse fibers. The fractional anisotropy (FA) derived from sequence C (b=1 000s/mm2, spatial resolution=0.55 mm×0.55 mm×2.5 mm, direction number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By comparison, the high resolution and the FA with high contrast of gray matter and white matter derived from sequence D (b=800 s/mm2, spatial resolution=1.0 mm×1.0 mm ×1.0 mm, numbers of direction=33, NSA=3) qualified in its application in tracking both thick and thin fibers, making it an optimal DTI setting for rhesus macaques. PMID:24866488

Essentialism in the absence of language? Evidence from rhesus monkeys (Macaca mulatta).

PubMed

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

2010-07-01

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 category. In two experiments, monkeys watched as an experimenter visually transformed a familiar fruit (e.g. apple) into a new kind of fruit (e.g. coconut) either by placing a fruit exterior over the original, or by removing an exterior shell and revealing the inside kind of fruit. The experimenter then pretended to place an inside piece of the transformed fruit into a box which the monkey was allowed to search. Results indicated that monkeys searched the box longer when they found a piece of fruit inconsistent with the inside kind, suggesting that the monkeys expected that the inside of the transformed fruit would taste like the innermost kind they saw. These results suggest that monkeys may share at least one aspect of psychological essentialism: they maintain category-specific expectations about an object's internal properties even when that object's external properties change. These results therefore suggest that some essentialist expectations may emerge in the absence of language, and thus raise the possibility that such tendencies may emerge earlier in human development than has previously been considered.

Septic arthritis due to moraxella osloensis in a rhesus macaque (Macaca mulatta).

PubMed

Wren, Melissa A; Caskey, John R; Liu, David X; Embers, Monica E

2013-01-01

A 5.5-y-old Chinese-origin female rhesus macaque (Macaca mulatta) presented for bilateral hindlimb lameness. The primate had been group-reared in an SPF breeding colony and was seronegative for Macacine herpesvirus 1, SIV, simian retrovirus type D, and simian T-lymphotropic virus. The macaque's previous medical history included multiple occasions of swelling in the left tarsus, and trauma to the right arm and bilateral hands. In addition, the macaque had experienced osteomyelitis of the left distal tibia and rupture of the right cranial cruciate ligament that had been surgically repaired. Abnormal physical examination findings on presentation included a thin body condition, mild dehydration, and bilaterally swollen stifles that were warm to the touch, with the right stifle more severely affected. Mild instability in the left stifle was noted, and decreased range of motion and muscle atrophy were present bilaterally. Hematologic findings included marked neutrophilia and lymphopenia and moderate anemia. Arthrocentesis and culture of joint fluid revealed Moraxella-like organisms. Treatment with enrofloxacin was initiated empirically and subsequently switched to cephalexin, which over time alleviated the joint swelling and inflammation. Definitive diagnosis of Moraxella osloensis septic arthritis was made through isolation of the organism and sequencing of the 16S rDNA region. To our knowledge, this report is the first description of Moraxella osloensis septic arthritis in a rhesus macaque.

Septic Arthritis Due to Moraxella osloensis in a Rhesus Macaque (Macaca mulatta)

PubMed Central

Wren, Melissa A; Caskey, John R; Liu, David X; Embers, Monica E

2013-01-01

A 5.5-y-old Chinese-origin female rhesus macaque (Macaca mulatta) presented for bilateral hindlimb lameness. The primate had been group-reared in an SPF breeding colony and was seronegative for Macacine herpesvirus 1, SIV, simian retrovirus type D, and simian T-lymphotropic virus. The macaque's previous medical history included multiple occasions of swelling in the left tarsus, and trauma to the right arm and bilateral hands. In addition, the macaque had experienced osteomyelitis of the left distal tibia and rupture of the right cranial cruciate ligament that had been surgically repaired. Abnormal physical examination findings on presentation included a thin body condition, mild dehydration, and bilaterally swollen stifles that were warm to the touch, with the right stifle more severely affected. Mild instability in the left stifle was noted, and decreased range of motion and muscle atrophy were present bilaterally. Hematologic findings included marked neutrophilia and lymphopenia and moderate anemia. Arthrocentesis and culture of joint fluid revealed Moraxella-like organisms. Treatment with enrofloxacin was initiated empirically and subsequently switched to cephalexin, which over time alleviated the joint swelling and inflammation. Definitive diagnosis of Moraxella osloensis septic arthritis was made through isolation of the organism and sequencing of the 16S rDNA region. To our knowledge, this report is the first description of Moraxella osloensis septic arthritis in a rhesus macaque. PMID:24326229

Geometric distortions affect face recognition in chimpanzees (Pan troglodytes) and monkeys (Macaca mulatta).

PubMed

Taubert, Jessica; Parr, Lisa A

2011-01-01

All primates can recognize faces and do so by analyzing the subtle variation that exists between faces. Through a series of three experiments, we attempted to clarify the nature of second-order information processing in nonhuman primates. Experiment one showed that both chimpanzees (Pan troglodytes) and rhesus monkeys (Macaca mulatta) tolerate geometric distortions along the vertical axis, suggesting that information about absolute position of features does not contribute to accurate face recognition. Chimpanzees differed from monkeys, however, in that they were more sensitive to distortions along the horizontal axis, suggesting that when building a global representation of facial identity, horizontal relations between features are more diagnostic of identity than vertical relations. Two further experiments were performed to determine whether the monkeys were simply less sensitive to horizontal relations compared to chimpanzees or were instead relying on local features. The results of these experiments confirm that monkeys can utilize a holistic strategy when discriminating between faces regardless of familiarity. In contrast, our data show that chimpanzees, like humans, use a combination of holistic and local features when the faces are unfamiliar, but primarily holistic information when the faces become familiar. We argue that our comparative approach to the study of face recognition reveals the impact that individual experience and social organization has on visual cognition.

Calming an aggressor through spontaneous post-conflict triadic contacts: Appeasement in Macaca tonkeana.

PubMed

Pallante, Virginia; Stanyon, Roscoe; Palagi, Elisabetta

2018-04-17

Peaceful third-party interventions usually occur after an aggressive encounter and can be directed toward the victim or the aggressor. Macaca tonkeana, a cercopithecine species characterized by high levels of tolerance, frequently engage in consolatory contacts, which both calm the victim and reduce the probability of further attacks against him/her. Other post-conflict affiliative interventions such as reconciliation and quadratic affiliation are also common in this species. However, little attention has been given to contacts directed toward the aggressor. Here, we explore the role of bystander affiliative interventions toward the aggressor in influencing the affective state of the aggressor and the consequences of triadic interventions at group level. We found that triadic post-conflict affiliation occurred independently from the intensity of the conflict and that it was more frequent in absence of the conciliatory contact between the opponents (reconciliation). Bystanders showed a higher amount of post-conflict affiliation toward low ranking aggressors. Post-conflict triadic affiliation functioned as a tension reduction mechanism by lowering the arousal of the aggressor, which less frequently engaged in renewed aggression. All these findings suggest that post-conflict triadic contacts in Tonkean macaques can be considered as a strategic mechanism to calm the aggressor and reduce the risk of retaliatory aggression. © 2018 Wiley Periodicals, Inc.

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

PubMed

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.

[Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer].

PubMed

Qin, Zu-Xing; Huang, Gao-Bo; Luo, Jun; Ning, Shu-Fang; Lu, Sheng-Sheng; Lu, Ke-Huan

2012-03-01

Long-tailed macaque-pig interspecies somatic cell nuclear transfer (iSCNT) is beneficial to yield embryonic stem cells from iSCNT embryos with similar genetic background as human, which can be used as materials for medical and basic research. The primary objective of this study was to investigate the effects of concentrations and treatment duration of two histone deacetylase inhibitors-Trichostatin A (TSA) and Valproic acid (VPA) and two different embryo culture media (PZM-3 and HECM-10) on the in vitro development of iSCNT embryos. The results suggested that when PZM-3 was used as the embryo culture medium, the blastocyst rate of 10 nmol/L TSA treatment for 48 h was significantly higher than the control group (22.78% vs 9.86%, P< 0.05). However, neither in PZM-3 nor in HECM-10, 2-10 mmol/L VPA treatment did not increase the in vitro developmental potential of iSCNT embryos. It was concluded that TSA treatment could enhance the in vitro developmental potential of long-tailed macaque-pig iSCNT embryos.

Assessment of early placental development in the cynomolgus monkey (Macaca fascicularis) using colour and pulsed wave Doppler sonography.

PubMed

Nimrod, C; Simpson, N; Hafner, T; de Vermette, R; Fournier, J; Coady, L; Baccanale, C

1996-04-01

Colour flow mapping and pulsed wave Doppler were used to assess the process of placental growth and development in the cynomolgus monkey from 32 to 71 days gestational age. Fetal and maternal vessels were reliably visualised and insonated. Accurate longitudinal non-invasive assessment of placentation is possible using this technique.

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

DTIC Science & Technology

2011-11-01

verbal behavior (for example, reading, writing, speaking) and refined motor performances (for example, driving a car, brushing one’s teeth , playing a...food daily (no. 8714 Teklad 15% Monkey Diet , Harlan Laboratories, Indianapolis, IN, and fresh fruit and vegetables) to maintain body weight at

Development of breeding populations of rhesus macaques (Macaca mulatta) that are specific pathogen-free for rhesus cytomegalovirus.

PubMed

Barry, Peter A; Strelow, Lisa

2008-02-01

Development of breeding colonies of rhesus macaques (Macaca mulatta) that are specific pathogen-free (SPF) for rhesus cytomegalovirus (RhCMV) is relatively straightforward and requires few modifications from current SPF programs. Infants separated from the dam at or within a few days of birth and cohoused with similarly treated animals remain RhCMV seronegative indefinitely, provided they are never directly or indirectly exposed to a RhCMV-infected monkey. By systematically cohousing seronegative animals into larger social cohorts, breeding populations of animals SPF for RhCMV can be established. The additional costs involved in expanding the current definition of SPF status to include RhCMV are incremental compared with the money already being spent on existing SPF efforts. Moreover, the large increase in research opportunities available for RhCMV-free animals arguably would far exceed the development costs. Potential new areas of research and further expansion of existing research efforts involving these newly defined SPF animals would have direct implications for improvements in human health.

Particle-to-PFU ratio of Ebola virus influences disease course and survival in cynomolgus macaques.

PubMed

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; Griffiths, Anthony

2015-07-01

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. 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 identical stocks

Zolpidem generalization and antagonism in male and female cynomolgus monkeys trained to discriminate 1.0 or 2.0 g/kg ethanol.

PubMed

Helms, Christa M; Rogers, Laura S M; Waters, Courtney A; Grant, Kathleen A

2008-07-01

The subtypes of gamma-aminobutyric acid (GABA)(A) receptors mediating the discriminative stimulus effects of ethanol in nonhuman primates are not completely identified. The GABA(A) receptor positive modulator zolpidem has high, intermediate, and low activity at receptors containing alpha(1), alpha(2/3), and alpha(5) subunits, respectively, and partially generalizes from ethanol in several species. The partial inverse agonist Ro15-4513 has the greatest affinity for alpha(4/6)-containing receptors, higher affinity for alpha(5)- and lower, but equal, affinity for alpha(1)- and alpha(2/3)-, containing GABA(A) receptors, and antagonizes the discriminative stimulus effects of ethanol. This study assessed Ro15-4513 antagonism of the generalization of zolpidem from ethanol in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 g/kg (n = 10) or 2.0 g/kg (n = 7) ethanol (i.g.) from water with a 30-minute pretreatment interval. Zolpidem (0.017 to 5.6 mg/kg, i.m.) completely generalized from ethanol (>or=80% of total session responses on the ethanol-appropriate lever) for 6/7 monkeys trained to discriminate 2.0 g/kg and 4/10 monkeys trained to discriminate 1.0 g/kg ethanol. Zolpidem partially generalized from 1.0 or 2.0 g/kg ethanol in 6/7 remaining monkeys. Ro15-4513 (0.003 to 0.30 mg/kg, i.m., 5-minute pretreatment) shifted the zolpidem dose-response curve to the right in all monkeys showing generalization. Analysis of apparent pK(B) from antagonism tests suggested that the discriminative stimulus effects of ethanol common with zolpidem are mediated by low-affinity Ro15-4513 binding sites. Main effects of sex and training dose indicated greater potency of Ro15-4513 in males and in monkeys trained to discriminate 1.0 g/kg ethanol. Ethanol and zolpidem share similar discriminative stimulus effects most likely through GABA(A) receptors that contain alpha(1) subunits, however, antagonism by Ro15-4513 of zolpidem generalization

Highly heterogeneous bacterial communities associated with the South China Sea reef corals Porites lutea, Galaxea fascicularis and Acropora millepora.

PubMed

Li, Jie; Chen, Qi; Zhang, Si; Huang, Hui; Yang, Jian; Tian, Xin-Peng; Long, Li-Juan

2013-01-01

Coral harbor diverse and specific bacteria play significant roles in coral holobiont function. Bacteria associated with three of the common and phylogenetically divergent reef-building corals in the South China Sea, Porites lutea, Galaxea fascicularis and Acropora millepora, were investigated using 454 barcoded-pyrosequencing. Three colonies of each species were sampled, and 16S rRNA gene libraries were constructed individually. Analysis of pyrosequencing libraries showed that bacterial communities associated with the three coral species were more diverse than previous estimates based on corals from the Caribbean Sea, Indo-Pacific reefs and the Red Sea. Three candidate phyla, including BRC1, OD1 and SR1, were found for the first time in corals. Bacterial communities were separated into three groups: P. lutea and G. fascicular, A. millepora and seawater. P. lutea and G. fascicular displayed more similar bacterial communities, and bacterial communities associated with A. millepora differed from the other two coral species. The three coral species shared only 22 OTUs, which were distributed in Alphaproteobacteria, Deltaproteobacteria, Gammaproteobacteria, Chloroflexi, Actinobacteria, Acidobacteria and an unclassified bacterial group. The composition of bacterial communities within each colony of each coral species also showed variation. The relatively small common and large specific bacterial communities in these corals implies that bacterial associations may be structured by multiple factors at different scales and that corals may associate with microbes in terms of similar function, rather than identical species.

Reactive amyloidosis associated with ischial callosititis: a report with histology of ischial callosities in rhesus macaques (Macaca mulatta)

PubMed Central

Liu, David X.; Gilbert, Margaret H.; Wang, Xiaolei; Didier, Peter J.; Veazey, Ronald S.

2014-01-01

Ischial callosities have received little attention in veterinary medicine even though they are distinguishing anatomic organs. The organs are characterized by a pair of hairless pads of thickened epidermis, located bilaterally in the gluteal region, which overlay the tuberosities of the ischia of all Old World monkeys, gibbons, and siamangs. The current report describes a case of reactive amyloidosis associated with ischial callosititis in a rhesus macaque (Macaca mulatta). Amyloid A (AA) protein was found in the liver, spleen, small intestine, mesenteric lymph nodes, and ischial callosities by histology, Congo red stain, and immunohistochemistry. Confocal microscopy showed that many cluster of differentiation (CD)68-positive macrophages within the ischial callosities contained intracellular AA protein, which suggests that CD68-positive macrophages have an important role in the pathogenesis of reactive amyloidosis in nonhuman primates. The normal histology of ischial callosities of rhesus macaques is also documented in this report. PMID:23104953

Reactive amyloidosis associated with ischial callosititis: a report with histology of ischial callosities in rhesus macaques (Macaca mulatta).

PubMed

Liu, David X; Gilbert, Margaret H; Wang, Xiaolei; Didier, Peter J; Veazey, Ronald S

2012-11-01

Ischial callosities have received little attention in veterinary medicine even though they are distinguishing anatomic organs. The organs are characterized by a pair of hairless pads of thickened epidermis, located bilaterally in the gluteal region, which overlay the tuberosities of the ischia of all Old World monkeys, gibbons, and siamangs. The current report describes a case of reactive amyloidosis associated with ischial callosititis in a rhesus macaque (Macaca mulatta). Amyloid A (AA) protein was found in the liver, spleen, small intestine, mesenteric lymph nodes, and ischial callosities by histology, Congo red stain, and immunohistochemistry. Confocal microscopy showed that many cluster of differentiation (CD)68-positive macrophages within the ischial callosities contained intracellular AA protein, which suggests that CD68-positive macrophages have an important role in the pathogenesis of reactive amyloidosis in nonhuman primates. The normal histology of ischial callosities of rhesus macaques is also documented in this report.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

PubMed

MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

Neonatal imitation predicts infant rhesus macaque (Macaca mulatta) social and anxiety-related behaviours at one year

PubMed Central

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

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

PubMed

Andrade, Márcia Cristina Ribeiro; Gabeira, Sanny Cerqueira de Oliveira; Abreu-Lopes, Danielle; Esteves, Wagner Thadeu Cardoso; Vilardo, Mônica de Castro Britto; Thomé, Jacqueline D'arc da Silva; Cabello, Pedro Hernan; Lauria-Filgueiras, Ana Luzia

2007-02-01

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.

Asymmetries in mother-infant behaviour in Barbary macaques (Macaca sylvanus)

PubMed Central

Spiezio, Caterina; Hopkins, William Donald

2018-01-01

Asymmetries in the maternal behaviour and anatomy might play an important role in the development of primate manual lateralization. In particular, early life asymmetries in mother’s and infant’s behaviour have been suggested to be associated with the development of the hand preference of the offspring. The aim of this study was to investigate the presence of behavioural asymmetries in different behavioural categories of mother-infant dyads of zoo-living Barbary macaques (Macaca sylvanus). The study subjects were 14 Barbary macaques involved in seven mother-infant dyads housed in Parco Natura Viva, Italy. For the mothers, bouts of hand preference for maternal cradling and infant retrieval were collected. For the infants, we focused on nipple preference and hand preference for clinging on mother ventrum. Moreover, we collected bouts of hand preference for food reaching in both groups. No significant group-level bias was found for any of the behavioural categories in either mothers or infants. However, at the individual level, six out of seven mothers showed a significant cradling bias, three toward the right hand and three toward the left hand. Moreover, all infants showed a significant nipple preference, six toward the mother’s right nipple, one toward the left nipple. Furthermore, a significant correlation was found between the infant nipple preference and their hand preference for food reaching, suggesting that maternal environment rather than behaviour might affect the development of hand preference in Old World monkeys. Our findings seem partially to add to previous literature on perceptual lateralization in different species of non-primate mammals, reporting a lateral bias in mother-infant interactions. Given the incongruences between our study and previous research in great apes and humans, our results seem to suggest possible phylogenetic differences in the lateralization of mothers and infants within the Primates order. PMID:29761052

Plasmodium knowlesi: from Malaysia, a novel health care threat.

PubMed

Sabbatani, Sergio; Fiorino, Sirio; Manfredi, Roberto

2012-03-01

Epidemic foci of Plasmodium knowlesi malaria have been identified during the past ten years in Malaysia, in particular in the States of Sarawak and Sabah (Malaysia Borneo), and in the Pahang region (peninsular Malaysia). Based on a review of the available recent international literature, the authors underline the importance of molecular biology examinations, polymerase chain reactions (PCR), performed with primers specific for P. knowlesi, since the current microscopic examination (haemoscope) may fail to distinguish P. knowlesi from Plasmodium malariae, due to the very similar appearance of the two parasites. P. knowlesi has been described as the causal agent of life-threatening and lethal forms of malaria: its clinical picture is more severe when compared with that of P. malariae, since the disease is characterized by greater parasitaemia, as opposed to that documented in the course of P. malariae disease. The most effective carrier is Anopheles leucosphyrus: this mosquito is attracted by both humans and monkeys. Among primates, the natural hosts of P. knowlesi are Macaca fascicularis and Macaca nemestina, while Saimiri scirea and Macaca mulatta, which cannot become infected in nature, may be useful in experimental models. When underlining the potentially severe evolution, we note the key role played by prompt disease recognition, which is expected to be more straightforward in patients monitored in endemic countries at high risk, but should be carefully implemented for subjects being admitted to hospital in Western countries suffering from the typical signs and symptoms of malaria, after travelling in South-East Asia where they were engaged in excursions in the tropical forest (trekking, and similar outdoor activities). In these cases, the diagnosis should be prompt, and suitable treatment should follow. According to data in the literature, in non-severe cases chloroquine proves very effective against P. knowlesi, achieving the disappearance of signs and

Locally infiltrative ameloblastic fibroma in a rhesus macaque (Macaca mulatta) with characterizations of its proliferating activity and biological behavior

PubMed Central

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.

2014-01-01

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. PMID:22529141

Individual differences in Scanpaths correspond with serotonin transporter genotype and behavioral phenotype in rhesus monkeys (Macaca mulatta).

PubMed

Gibboni, Robert R; Zimmerman, Prisca E; Gothard, Katalin M

2009-01-01

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.

Establishment of a translational endothelial cell model using directed differentiation of induced pluripotent stem cells from Cynomolgus monkey.

PubMed

Thoma, Eva C; Heckel, Tobias; Keller, David; Giroud, Nicolas; Leonard, Brian; Christensen, Klaus; Roth, Adrian; Bertinetti-Lapatki, Cristina; Graf, Martin; Patsch, Christoph

2016-10-25

Due to their broad differentiation potential, pluripotent stem cells (PSCs) offer a promising approach for generating relevant cellular models for various applications. While human PSC-based cellular models are already advanced, similar systems for non-human primates (NHPs) are still lacking. However, as NHPs are the most appropriate animals for evaluating the safety of many novel pharmaceuticals, the availability of in vitro systems would be extremely useful to bridge the gap between cellular and animal models. Here, we present a NHP in vitro endothelial cell system using induced pluripotent stem cells (IPSCs) from Cynomolgus monkey (Macaca fascicularis). Based on an adapted protocol for human IPSCs, we directly differentiated macaque IPSCs into endothelial cells under chemically defined conditions. The resulting endothelial cells can be enriched using immuno-magnetic cell sorting and display endothelial marker expression and function. RNA sequencing revealed that the differentiation process closely resembled vasculogenesis. Moreover, we showed that endothelial cells derived from macaque and human IPSCs are highly similar with respect to gene expression patterns and key endothelial functions, such as inflammatory responses. These data demonstrate the power of IPSC differentiation technology to generate defined cell types for use as translational in vitro models to compare cell type-specific responses across species.

Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates.

PubMed

Deushi, Michiyo; Osaka, Mizuko; Nakano, Kaku; Osada, Kyoichi; Egashira, Kensuke; Yoshida, Masayuki

2016-10-01

Oxidized cholesterol (oxysterols) plays an important and multifaceted role in lipid metabolism. Here we examined whether dietary oxysterols accelerate hepatic lipid accumulation and inflammation in nonhuman primates. We also examined the effect of the Niemann-Pick C1-like1 inhibitor, ezetimibe (Ez). Macaca fascicularis (5-year-old males) were fed either regular cholesterol + high-fat diet (control-HFD) or oxysterols + high-fat diet (ox-HFD; with 0.015% of oxysterols cholesterol) for 24 weeks. Compared with control-HFD, ox-HFD did not affect plasma lipid levels, but it did affect hepatic lipid levels [total cholesterol, 40.9 mg·g -1 (ox-HFD) versus 3.2 (control-HFD) mg·g -1 ; triglycerides, 28.0 (ox-HFD) versus 5.7 (control-HFD) mg·g -1 ]. Ox-HFD increased lipid accumulation as well as recruitment of inflammatory cells when compared to control-HFD. We then examined the effects of Ez, 0.2 mg·kg -1 ·day -1 for 12 weeks. In addition to a significant reduction in dyslipidemia, Ez alleviated biochemical and pathological aspects of steatosis. Dietary oxysterols aggravate steatosis in nonhuman primates. Treatment with Ez may be a novel therapeutic approach to NAFLD by alleviating dyslipidemia.

Comparative community-level associations of helminth infections and microparasite shedding in wild long-tailed macaques in Bali, Indonesia.

PubMed

Wilcox, Justin J S; Lane-Degraaf, Kelly E; Fuentes, Agustin; Hollocher, Hope

2015-03-01

Helminthes have the capacity to modulate host immunity, leading to positive interactions with coinfecting microparasites. This phenomenon has been primarily studied during coinfections with a narrow range of geo-helminthes and intracellular microparasites in human populations or under laboratory conditions. Far less is known regarding differences in coinfection dynamics between helminth types, the range of microparasites that might be affected or the overall community-level effects of helminth infections on microparasites in wild systems. Here, we analysed the presence/absence and abundance patterns of enteric parasites in long-tailed macaques (Macaca fascicularis) on the island of Bali, Indonesia, to assess whether naturally occurring helminth infections were associated with increased shedding of the most common intracellular (Cryptosporidium spp., Isospora spp.) and extracellular (Entamoeba spp., Giardia spp.) microparasites. We also comparatively assessed the statistical correlations of different helminth taxa with microparasite shedding to determine if there were consistent relationships between the specific helminth taxa and microparasites. Helminth infections were associated with increased shedding of both intracellular and extracellular microparasites. Platyhelminthes repeatedly displayed strong positive correlations with several microparasites; while nematodes did not. Our results indicate that helminthes can influence microparasite community shedding dynamics under wild conditions, but that trends may be driven by a narrow range of helminthes.

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

PubMed

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

2018-02-01

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

Fatty liver promotes fibrosis in monkeys consuming high fructose.

PubMed

Cydylo, Michael A; Davis, Ashley T; Kavanagh, Kylie

2017-02-01

Nonalcoholic fatty liver diseases (NAFLD) are related to development of liver fibrosis which currently has few therapeutic options. Rodent models of NAFLD inadequately model the fibrotic aspects of the disease and fail to demonstrate the spectrum of cardiometabolic diseases without genetic manipulation. This study aimed to document a monkey model of fatty liver and fibrosis, which naturally develop cardiometabolic disease pathophysiologies. Twenty-seven cynomolgus monkeys (Macaca fascicularis) fed diets either low or high in simple carbohydrates, supplied as fructose [control and high-fructose diet (HRr)], on low-fat, cholesterol-free background were studied. The HFr was consumed for up to 7 years, and liver tissue was histologically evaluated for fat and fibrosis extent. The HFr diet increased steatosis, and its extent was related to duration of fructose exposure. Lipid droplet size also increased with HFr duration; however, compared with control, the lipid droplets were smaller on average. Fibrosis extent was significantly greater with fructose feeding and was predicted by fructose exposure, extent of fatty liver, and age. These data are the first to demonstrate that high-carbohydrate diets alone can generate both liver fat and fibrosis and thus allow further study of mechanisms and therapeutic options in the translational animal model. © 2017 The Obesity Society.

Influence of immediate loading on provisional restoration in dental implant stability

NASA Astrophysics Data System (ADS)

Ikbal, M.; Odang, R. W.; Indrasari, M.; Dewi, R. S.

2017-08-01

The success of dental implant treatment is determined by the primary stability at placement. One factor that could influence this stability is occlusal loading through provisional restoration. Two types of loading protocols are usually used: immediate and delayed loading. However, some controversies remain about the influence of occlusal loading on implant stability. Therefore, the influence of immediate loading on implant stability must be studied. An animal study was conducted by placing nine dental implants in the mandibular jaw of three Macaca fascicularis. Provisional restorations with various occlusal contacts (no, light, and normal contact) were placed on the implant. The implant stability was measured using the Ostell ISQ three times: immediately (baseline) and at the first and second months after implant placement. The implant stability between implants with no and normal occlusal contact as well as light and normal occlusal contact showed significant differences (p < 0.05) at the first and second months after implant placement. However, no significant increase (p > 0.05) in implant stability was seen at the baseline and the first and second months after implant placement for all occlusal contact groups. Immediate loading influenced the implant stability, and provisional restoration of implant without occlusal contact showed the highest implant stability.

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

USGS Publications Warehouse

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.

Pharmacokinetics and pharmacodynamics of injectable testosterone undecanoate in castrated cynomolgus monkeys (Macaca fascicularis) are independent of different oil vehicles.

PubMed

Wistuba, Joachim; Marc Luetjens, C; Kamischke, Axel; Gu, Yi-Qun; Schlatt, Stefan; Simoni, Manuela; Nieschlag, Eberhard

2005-08-01

Testosterone undecanoate (TU) dissolved in soybean oil was developed in China to improve the pharmacokinetics of this testosterone ester in comparison with TU in castor or tea seed oil. As a pre-clinical primate model, three groups of five castrated cynomolgus macaques received either a single intramuscular injection of 10 mg/kg body weight TU in soybean oil, in tea seed oil, or in castor oil (equals 6.3 mg pure T/kg body weight for all preparations). Testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone as well as prostate volume, body weight and ejaculate weight were evaluated. After injection supraphysiological testosterone levels were induced. There were no significant differences in the pharmacokinetics of the three TU preparations for testosterone and estradiol. The gonadotropin levels showed a high individual variation. Prostate volumes increased equally in all groups after administration and declined to castrate level afterwards. The results suggest that TU in soybean oil produces similar effects as TU in the other vehicles. This study in non-human primates provides no objection to testing of this new preparation in humans.

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences

PubMed Central

Xue, Cheng; Raveendran, Muthuswamy; Harris, R. Alan; Fawcett, Gloria L.; Liu, Xiaoming; White, Simon; Dahdouli, Mahmoud; Rio Deiros, David; Below, Jennifer E.; Salerno, William; Cox, Laura; Fan, Guoping; Ferguson, Betsy; Horvath, Julie; Johnson, Zach; Kanthaswamy, Sree; Kubisch, H. Michael; Liu, Dahai; Platt, Michael; Smith, David G.; Sun, Binghua; Vallender, Eric J.; Wang, Feng; Wiseman, Roger W.; Chen, Rui; Muzny, Donna M.; Gibbs, Richard A.; Yu, Fuli; Rogers, Jeffrey

2016-01-01

Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease. PMID:27934697

Reference Intervals for Preprandial and Postprandial Serum Bile Acid in Adult Rhesus Macaques (Macaca mulatta)

PubMed Central

Lemoy, Marie-Josee MF; Westworth, Diccon R; Ardeshir, Amir; Tarara, Ross P

2013-01-01

The purpose of this study was to determine the 12-h fasting preprandial and 2-h postprandial serum bile acid concentration (SBAC) reference intervals for healthy, adult rhesus macaques (Macaca mulatta). We hypothesized that the mean 2-h postprandial SBAC would be significantly higher than the mean preprandial SBAC. We included 40 (24 male, 16 female) macaques after confirming that their health records, physical examinations, CBC, serum chemistry panels, and urinalyses were all within normal limits. In addition, hepatitis A titers were determined, an ultrasound examination of the liver was performed, and two 16-gauge ultrasound guided percutaneous liver biopsies were collected and submitted for histopathology. Macaques were confirmed healthy according to hepatitis A screens and sonographic and histologic evaluation of hepatic tissue. Within 2 wk of the screening procedures, preprandial and postprandial SBACs were measured. Preprandial SBAC (mean ± 1 SD) was 11.1 ± 1.9 µmol/L and postprandial SBAC was 19.7 ± 8.0 µmol/L, which was significantly higher than the preprandial value. Sex and hepatitis titers did not significantly influence preprandial and postprandial SBAC. The current study indicates that the SBAC reference values for rhesus macaques are higher than those reported for humans and companion animals. PMID:23849441

[Comparisons of aggressive behavior for Tibetan Macaques (Macaca thibetana) to tourists from Mt. Huangshan, China].

PubMed

Ji, Huan; Li, Jin-Hua; Sun, Bing-Hua; Zhu, Yong

2010-08-01

To investigate the relationship between monkey-human aggressive behaviors and age/sex classes of monkey (initiator) and human (recipient), by using all-occurrence sampling and continuous recording, we evaluated the monkey-human aggressive behaviors between macaques (Macaca thibetana) and tourists at Mt. Huangshan in two periods (Nov.-Dec.2008 and Apr.-May 2009). After we divide the aggression into three types according to the dangerous level to tourists, some significant patterns were observed.Our observations indicate that Tibetan macaques respond differently to human according to the age/sex classes involved. On one hand, We found that the adult male monkeys tend to be more aggressive than expected (P<0.01), while the adult female monkeys and immature monkeys participated in AGIII behaviors (threat) less than expected (P<0.01); On the other hand, The adult male human received more aggressive behaviors than expected (P<0.01), while the adult female human and child received less aggressive in AGIII behaviors (threat) (P<0.01). Our results provide not only a scientific basis for the management advice that adult male monkeys and adult male human should be given special attention, but also a good management model of Huangshan for other primate tourist exploring places.

Reference intervals for preprandial and postprandial serum bile acid in adult rhesus macaques (Macaca mulatta).

PubMed

Lemoy, Marie-Josee M F; Westworth, Diccon R; Ardeshir, Amir; Tarara, Ross P

2013-07-01

The purpose of this study was to determine the 12-h fasting preprandial and 2-h postprandial serum bile acid concentration (SBAC) reference intervals for healthy, adult rhesus macaques (Macaca mulatta). We hypothesized that the mean 2-h postprandial SBAC would be significantly higher than the mean preprandial SBAC. We included 40 (24 male, 16 female) macaques after confirming that their health records, physical examinations, CBC, serum chemistry panels, and urinalyses were all within normal limits. In addition, hepatitis A titers were determined, an ultrasound examination of the liver was performed, and two 16-gauge ultrasound guided percutaneous liver biopsies were collected and submitted for histopathology. Macaques were confirmed healthy according to hepatitis A screens and sonographic and histologic evaluation of hepatic tissue. Within 2 wk of the screening procedures, preprandial and postprandial SBACs were measured. Preprandial SBAC (mean ± 1 SD) was 11.1 ± 1.9 μmol/L and postprandial SBAC was 19.7 ± 8.0 μmol/L, which was significantly higher than the preprandial value. Sex and hepatitis titers did not significantly influence preprandial and postprandial SBAC. The current study indicates that the SBAC reference values for rhesus macaques are higher than those reported for humans and companion animals.

Population density-dependent hair cortisol concentrations in rhesus monkeys (Macaca mulatta)

PubMed Central

Dettmer, A.M.; Novak, M.A.; Meyer, J.S.; Suomi, S.J.

2014-01-01

Summary Population density is known to influence acute measures of hypothalamic-pituitary-adrenal (HPA) axis activity in a variety of species, including fish, deer, birds, and humans. However, the effects of population density on levels of chronic stress are unknown. Given the fact that exposure to chronically elevated levels of circulating glucocorticoids results in a host of health disparities in animals and humans alike, it is important to understand how population density may impact chronic stress. We assessed hair cortisol concentrations (HCCs), which are reliable indicators of chronic HPA axis activity, in rhesus monkeys (Macaca mulatta) to determine the influence of population density on these values. In Experiment 1, we compared HCCs of monkeys living in high-density (HD; 1 monkey/0.87m2) and low-density (LD; 1 monkey/63.37m2) environments (N=236 hair samples) and found that HD monkeys exhibited higher hair cortisol across all age categories (infant, juvenile, young adult, adult, and aged) except infancy and aged (F(5)=4.240, p=0.001), for which differences were nearly significant. HD monkeys also received more severe fight wounds than LD monkeys (χ2=26.053, p<0.001), though no effects of dominance status emerged. In Experiment 2, we examined how HCCs change with fluctuating population levels across five years in the adult LD monkeys (N=155 hair samples) and found that increased population density was significantly positively correlated with HCCs in this semi-naturalistic population (r(s)=0.975, p=0.005). These are the first findings to demonstrate that increased population density is associated with increased chronic, endogenous glucocorticoid exposure in a nonhuman primate species. We discuss the implications of these findings with respect to laboratory research, population ecology, and human epidemiology. PMID:24636502

Population density-dependent hair cortisol concentrations in rhesus monkeys (Macaca mulatta).

PubMed

Dettmer, A M; Novak, M A; Meyer, J S; Suomi, S J

2014-04-01

Population density is known to influence acute measures of hypothalamic-pituitary-adrenal (HPA) axis activity in a variety of species, including fish, deer, birds, and humans. However, the effects of population density on levels of chronic stress are unknown. Given the fact that exposure to chronically elevated levels of circulating glucocorticoids results in a host of health disparities in animals and humans alike, it is important to understand how population density may impact chronic stress. We assessed hair cortisol concentrations (HCCs), which are reliable indicators of chronic HPA axis activity, in rhesus monkeys (Macaca mulatta) to determine the influence of population density on these values. In Experiment 1, we compared HCCs of monkeys living in high-density (HD; 1 monkey/0.87m(2)) and low-density (LD; 1 monkey/63.37m(2)) environments (N=236 hair samples) and found that HD monkeys exhibited higher hair cortisol across all age categories (infant, juvenile, young adult, adult, and aged) except infancy and aged (F(5)=4.240, p=0.001), for which differences were nearly significant. HD monkeys also received more severe fight wounds than LD monkeys (χ(2)=26.053, p<0.001), though no effects of dominance status emerged. In Experiment 2, we examined how HCCs change with fluctuating population levels across 5 years in the adult LD monkeys (N=155 hair samples) and found that increased population density was significantly positively correlated with HCCs in this semi-naturalistic population (r(s)=0.975, p=0.005). These are the first findings to demonstrate that increased population density is associated with increased chronic, endogenous glucocorticoid exposure in a nonhuman primate species. We discuss the implications of these findings with respect to laboratory research, population ecology, and human epidemiology. Published by Elsevier Ltd.

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

PubMed

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

2015-10-01

Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

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

PubMed Central

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

2018-01-01

Objective Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. Approach To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency shift key modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3-V batteries for 2 hours of operation. Main results We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely-moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. Significance We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates which can potentially move systems neuroscience to a new direction by allowing to record neural signals while animals interact with their environment. PMID

Comparative sacral morphology and the reconstructed tail lengths of five extinct primates: Proconsul heseloni, Epipliopithecus vindobonensis, Archaeolemur edwardsi, Megaladapis grandidieri, and Palaeopropithecus kelyus.

PubMed

Russo, Gabrielle A

2016-01-01

This study evaluated the relationship between the morphology of the sacrum-the sole bony link between the tail or coccyx and the rest of the body-and tail length (including presence/absence) and function using a comparative sample of extant mammals spanning six orders (Primates, Carnivora, Rodentia, Diprotodontia, Pilosa, Scandentia; N = 472). Phylogenetically-informed regression methods were used to assess how tail length varied with respect to 11 external and internal (i.e., trabecular) bony sacral variables with known or suspected biomechanical significance across all mammals, only primates, and only non-primates. Sacral variables were also evaluated for primates assigned to tail categories ('tailless,' 'nonprehensile short-tailed,' 'nonprehensile long-tailed,' and 'prehensile-tailed'). Compared to primates with reduced tail lengths, primates with longer tails generally exhibited sacra having larger caudal neural openings than cranial neural openings, and last sacral vertebrae with more mediolaterally-expanded caudal articular surfaces than cranial articular surfaces, more laterally-expanded transverse processes, more dorsally-projecting spinous processes, and larger caudal articular surface areas. Observations were corroborated by the comparative sample, which showed that shorter-tailed (e.g., Lynx rufus [bobcat]) and longer-tailed (e.g., Acinonyx jubatus [cheetah]) non-primate mammals morphologically converge with shorter-tailed (e.g., Macaca nemestrina) and longer-tailed (e.g., Macaca fascicularis) primates, respectively. 'Prehensile-tailed' primates exhibited last sacral vertebrae with more laterally-expanded transverse processes and greater caudal articular surface areas than 'nonprehensile long-tailed' primates. Internal sacral variables performed poorly compared to external sacral variables in analyses of extant primates, and were thus deemed less useful for making inferences concerning tail length and function in extinct primates. The tails lengths of

First case of detection of Plasmodium knowlesi in Spain by Real Time PCR in a traveller from Southeast Asia.

PubMed

Ta, Tang Thuy-Huong; Salas, Ana; Ali-Tammam, Marwa; Martínez, María Del Carmen; Lanza, Marta; Arroyo, Eduardo; Rubio, Jose Miguel

2010-07-27

Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia. A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009. His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment. Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative. This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported. Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006. Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia. This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection. Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very

First case of detection of Plasmodium knowlesi in Spain by Real Time PCR in a traveller from Southeast Asia

PubMed Central

2010-01-01

Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia. A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009. His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment. Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative. This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported. Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006. Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia. This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection. Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very

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

NASA Astrophysics Data System (ADS)

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

2015-10-01

Objective. Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. Approach. To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. Main results. We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. Significance. We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

Microvasculature of the Olfactory Organ in the Japanese Monkey (Macaca fuscata fuscata)

NASA Astrophysics Data System (ADS)

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.

Evidence that monkeys (Macaca tonkeana and Sapajus apella) read moves, but no evidence that they read goals.

PubMed

Costes-Thiré, Morgane; Levé, Marine; Uhlrich, Pierre; Pasquaretta, Cristian; De Marco, Arianna; Thierry, Bernard

2015-08-01

Whereas most experiments indicate that monkeys have no theory of mind, a study carried out by Wood and collaborators (2007) claimed that they can make inferences about the intentions of another individual. We applied the experimental procedure devised by these authors to investigate whether monkeys can recognize goal-directed actions. We tested 16 Tonkean macaques (Macaca tonkeana) and 12 tufted capuchin monkeys (Sapajus apella). Each subject was submitted to 24 trials in randomized order. The experimenter presented 2 containers, 1 of which was potentially baited with a food reward. After the experimenter had either intentionally or accidentally made an action on 1 of the containers, the subject was asked to select 1 of them. We found that individuals in both species failed to distinguish between accidental and intentional actions. However, they displayed a significant preference for the container touched by the experimenter in the hand conditions, and not in the elbow conditions. These results do not support those reported by Wood and collaborators, but they are consistent with other studies concluding that monkeys are not capable of mind reading. (c) 2015 APA, all rights reserved).

Bilateral neurotoxic amygdala lesions in rhesus monkeys (Macaca mulatta): Consistent pattern of behavior across different social contexts

PubMed Central

Machado, Christopher J.; Emery, Nathan J.; Capitanio, John P.; Mason, William A.; Mendoza, Sally P.; Amaral, David G.

2010-01-01

Although the amygdala has been repeatedly implicated in normal primate social behavior, great variability exists in the specific social and nonsocial behavioral changes observed after bilateral amygdala lesions in nonhuman primates. One plausible explanation pertains to differences in social context. To investigate this idea, we measured the social behavior of amygdala-lesioned and unoperated rhesus monkeys (Macaca mulatta) in two contexts. Animals interacted in four-member social groups over 32 test days. These animals were previously assessed in pairs (Emery et al., 2001), and were, therefore, familiar with each other at the beginning of this study. Across the two contexts, amygdala lesions produced a highly consistent pattern of social behavior. Operated animals engaged in more affiliative social interactions with control group partners than did control animals. In the course of their interactions, amygdala-lesioned animals also displayed an earlier decrease in nervous and fearful personality qualities than controls. The increased exploration and sexual behavior recorded for amygdala-lesioned animals in pairs was not found in the four-member groups. We conclude that the amygdala contributes to social inhibition and this function transcends various social contexts. PMID:18410164

Evaluation of cell sheet application on one wall bone defect in Macaca nemestrina through periostin expression

NASA Astrophysics Data System (ADS)

Tamin, R. Y.; Soeroso, Y.; Amir, L.; Idrus, E.

2017-08-01

Chronic periodontitis is an oral disease in which the destruction of periodontal tissue leads to tooth loss. Regenerative therapy for attachment cannot be applied to one wall bone defects owing to the minimal existing healthy bone. Tissue engineering in the form of cell sheets has been developed to overcome this limitation. In a previous study, cell sheet application to a one wall bone defect in Macaca nemestrina showed good clinical results. To evaluate the effectiveness of cell sheet application histologically, the level of periostin expression in the gingival crevicular fluid (GCF) of M. nemestrina was determined. Periostin is a 90-kDa protein that regulates coordination and interaction for regeneration and tissue repair. A laboratory observation study was performed to see the differences in periostin levels in samples collected from M. nemestrina’s GCF, where a cell sheet was applied to the bone defect. Gel electrophoresis with SDS-PAGE was performed to detect periostin expression based on its molecular weight and to compare the expression band between the cell sheet and the control at 1, 2, and 3 weeks after treatment. The gel electrophoresis result shows different thicknesses of the protein band around the molecular weight of periostin between the cell sheet groups.

Robust representations of individual faces in chimpanzees (Pan troglodytes) but not monkeys (Macaca mulatta).

PubMed

Taubert, Jessica; Weldon, Kimberly B; Parr, Lisa A

2017-03-01

Being able to recognize the faces of our friends and family members no matter where we see them represents a substantial challenge for the visual system because the retinal image of a face can be degraded by both changes in the person (age, expression, pose, hairstyle, etc.) and changes in the viewing conditions (direction and degree of illumination). Yet most of us are able to recognize familiar people effortlessly. A popular theory for how face recognition is achieved has argued that the brain stabilizes facial appearance by building average representations that enhance diagnostic features that reliably vary between people while diluting features that vary between instances of the same person. This explains why people find it easier to recognize average images of people, created by averaging multiple images of the same person together, than single instances (i.e. photographs). Although this theory is gathering momentum in the psychological and computer sciences, there is no evidence of whether this mechanism represents a unique specialization for individual recognition in humans. Here we tested two species, chimpanzees (Pan troglodytes) and rhesus monkeys (Macaca mulatta), to determine whether average images of different familiar individuals were easier to discriminate than photographs of familiar individuals. Using a two-alternative forced-choice, match-to-sample procedure, we report a behaviour response profile that suggests chimpanzees encode the faces of conspecifics differently than rhesus monkeys and in a manner similar to humans.

Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys

PubMed Central

Grant, Kathleen A.; Helms, Christa M.; Rogers, Laura S.M.; Purdy, Robert H.

2008-01-01

Positive modulation of GABAA and antagonism of NMDA receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol suggesting that these steroids may modulate ethanol addiction. The 4 isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (progesterone) [allopregnanolone (3α,5α-P), pregnanolone (3α,5β-P), epiallopregnanolone (3β,5α-P), epipregnanolone (3β,5β-P)], a synthetic analogue of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3α,5β-P HS)], and a structurally-similar, adrenally-derived steroid [3α-hydroxy-5-androstan-17-one (3α,5α-A, androsterone)], were assessed for ethanol-like discriminative stimulus effects 30 or 60 min after administration in male (n=9) and female (n=8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) with a 30-min pre-treatment interval. The 3α-hydroxysteroids completely substituted for ethanol (80% of cases) whereas the 3β-hydroxysteroids and 3α,5β-P HS rarely substituted for ethanol (6% of cases). There were no sex differences. Compared to monkeys trained to discriminate 2.0 g/kg ethanol, 3α,5β-P and 3α,5α-A substituted more potently in monkeys trained to discriminate 1.0 g/kg ethanol. Compared to the 5β-reduced isomer (3α,5β-P), the 5α isomer of pregnanolone (3α,5α-P) substituted for ethanol with 3–40-fold greater potency but was least efficacious in female monkeys trained to discriminate 2.0 g/kg ethanol. The data suggest that the discriminative stimulus effects of lower doses (1.0 g/kg) of ethanol are mediated to a greater extent by 3α,5β-P-and 3α,5α-A-sensitive receptors compared to higher doses (2.0 g/kg). Furthermore, the discriminative stimulus effects of ethanol appear to be mediated by activity at binding sites that are particularly sensitive to 3α,5α-P. PMID:18436788

Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys.

PubMed

Grant, Kathleen A; Helms, Christa M; Rogers, Laura S M; Purdy, Robert H

2008-07-01

Positive modulation of GABA(A) and antagonism of N-methyl-D-aspartate receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol, suggesting that these steroids may modulate ethanol addiction. The four isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (progesterone) [allopregnanolone (3alpha,5alpha-P), pregnanolone (3alpha,5beta-P), epiallopregnanolone (3beta,5alpha-P), and epipregnanolone (3beta,5beta-P)], a synthetic analog of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3alpha,5beta-P HS)], and a structurally similar, adrenally derived steroid [3alpha-hydroxy-5-androstan-17-one (3alpha,5alpha-A, androsterone)] were assessed for ethanol-like discriminative stimulus effects at 30 or 60 min after administration in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) with a 30-min pretreatment interval. The 3alpha-hydroxysteroids completely substituted for ethanol (80% of cases), whereas the 3beta-hydroxysteroids and 3alpha,5beta-P HS rarely substituted for ethanol (6% of cases). There were no sex differences. Compared with monkeys trained to discriminate 2.0 g/kg ethanol, 3alpha,5beta-P and 3alpha,5alpha-A substituted more potently in monkeys trained to discriminate 1.0 g/kg ethanol. Compared with the 5beta-reduced isomer (3alpha,5beta-P), the 5alpha isomer of pregnanolone (3alpha,5alpha-P) substituted for ethanol with 3 to 40-fold greater potency but was least efficacious in female monkeys trained to discriminate 2.0 g/kg ethanol. The data suggest that the discriminative stimulus effects of lower doses (1.0 g/kg) of ethanol are mediated to a greater extent by 3alpha,5beta-P- and 3alpha,5alpha-A-sensitive receptors compared with higher doses (2.0 g/kg). Furthermore, the discriminative stimulus effects of ethanol appear to be mediated by activity at

Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration.

PubMed

Grant, Kathleen A; Leng, Xiaoyan; Green, Heather L; Szeliga, Kendall T; Rogers, Laura S M; Gonzales, Steven W

2008-10-01

We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent "spree" drinking (intakes >4.0 g/kg/d). This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into

Drinking Typography Established by Scheduled Induction Predicts Chronic Heavy Drinking in a Monkey Model of Ethanol Self-Administration

PubMed Central

Grant, Kathleen A.; Leng, Xiaoyan; Green, Heather L.; Szeliga, Kendall T.; Rogers, Laura S. M.; Gonzales, Steven W.

2010-01-01

Background We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Methods Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Results Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent “spree” drinking (intakes >4.0 g/kg/d). Conclusion This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the

Chronic methylmercury exposure in the monkey (Macaca mulatta)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luschei, E.; Mottet, N.K.; Shaw, C.M.

1977-01-01

Small daily doses of methylmercury hydroxide were administered to rhesus monkeys for periods of up to 17 months. Behavioral tests of peripheral vision and of the accuracy and rapidity of hand movements did not disclose any early subtle deficits preceding the onset of obvious signs of neurotoxicity. These signs appeared suddenly and involved reduced food intake (anorexia), clumsiness of jumping, loss of fine control of the digits, and uncoordinated mastication. With a constant daily dose of 0.1 mg/kg or less, blood concentration of mercury reached a peak after about 2 months, and then decreased to about half the peak value.more » Subsequently, increasing the daily dose level above 0.1 mg/kg (range of 0.12 to 0.21 mg/kg) produced an increase of blood concentration which tended to stabilize in the range of 2.0 to 2.5 ppM. After several months at these elevated concentrations all animals exhibited signs of neurotoxicity.« less

Efficacy of Selective PDE4D Negative Allosteric Modulators in the Object Retrieval Task in Female Cynomolgus Monkeys (Macaca fascicularis)

PubMed Central

Sutcliffe, Jane S.; Beaumont, Vahri; Watson, James M.; Chew, Chang Sing; Beconi, Maria; Hutcheson, Daniel M.; Dominguez, Celia; Munoz-Sanjuan, Ignacio

2014-01-01

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. PMID:25050979

Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

NASA Technical Reports Server (NTRS)

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.

Social object play among young Japanese macaques (Macaca fuscata) in Arashiyama, Japan.

PubMed

Shimada, Masaki

2006-10-01

Social object play (SOP), i.e., social play using portable object(s), among young Japanese macaques (Macaca fuscata; 0-4 years old) in the Arashiyama E troop was studied using a modified sequence sampling method from July to October 2000. SOP was a relatively common activity for most of the young macaques and often continued for long periods. Participants used many kinds of object, including edible natural objects and artificial objects, such as plastic bottles, but they never used provisioned food or wild fruit in SOP bouts. An analysis of long bouts (>/=0.5 min) revealed the following interactive SOP features: (1) at any given time, participants used only one object, and only one participant held the object; (2) during SOP play-chasing, the object holder was likely to be chased by others; (3) during long bouts, the object changed hands frequently; and (4) agonistic competition for an object among young macaques was rare. Combinations of sexes, ages, relative ranks, or matrilines of the object holder and non-holder did not affect the tendency that the holder was chased by non-holder(s) during play-chasing. Even when there was a change in object holders, the repetitiveness of this interactive pattern, i.e., that the holder would be chased during SOP bouts, distinguished the SOP structure from that of other types of social play without object(s). General proximate social play mechanisms, such as self-handicapping or role taking, were associated with SOP. Other mechanisms that affected SOP included the following: (1) young macaques treated an object as a target in play competition, and (2) 'being the holder of a target object' was associated with the 'role of the chasee.'

A Behavioral Taxonomy of Loneliness in Humans and Rhesus Monkeys (Macaca mulatta)

PubMed Central

Capitanio, John P.; Hawkley, Louise C.; Cole, Steven W.; Cacioppo, John T.

2014-01-01

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 mechanistic

Early maternal rejection affects the development of monoaminergic systems and adult abusive parenting in rhesus macaques (Macaca mulatta).

PubMed

Maestripieri, Dario; Higley, J Dee; Lindell, Stephen G; Newman, Timothy K; McCormack, Kai M; Sanchez, Mar M

2006-10-01

This study investigated the effects of early exposure to variable parenting style and infant abuse on cerebrospinal fluid (CSF) concentrations of monoamine metabolites and examined the role of monoaminergic function in the intergenerational transmission of infant abuse in rhesus monkeys (Macaca mulatta). Forty-three infants reared by their biological mothers and 15 infants that were cross-fostered at birth and reared by unrelated mothers were followed longitudinally through their first 3 years of life or longer. Approximately half of the infants were reared by abusive mothers and half by nonabusive controls. Abused infants did not differ from controls in CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylgycol (MHPG). Abused infants, however, were exposed to higher rates of maternal rejection, and highly rejected infants had lower CSF 5-HIAA and HVA than low-rejection infants. The abused females who became abusive mothers in adulthood had lower CSF 5-HIAA than the abused females who did not. A similar trend was also observed among the cross-fostered females, suggesting that low serotonergic function resulting from early exposure to high rates of maternal rejection plays a role in the intergenerational transmission of infant abuse.

Factors increasing snake detection and perceived threat in captive rhesus macaques (Macaca mulatta).

PubMed

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. © 2013 Wiley Periodicals, Inc.

Sex and the stimulus-movement effect: Differences in acquisition of autoshaped responding in cynomolgus monkeys.

PubMed

Rice, Nathaniel C; Makar, Jennifer R; Myers, Todd M

2017-03-15

The stimulus-movement effect refers to the phenomenon in which stimulus discrimination or acquisition of a response is facilitated by moving stimuli as opposed to stationary stimuli. The effect has been found in monkeys, rats, and humans, but the experiments conducted did not provide adequate female representation to investigate potential sex differences. The current experiment analyzed acquisition of stimulus touching in a progressive series of classical conditioning procedures in cynomolgus monkeys (Macaca fascicularis) as a function of sex and stimulus movement. Classical conditioning tasks arrange two or more stimuli in relation to each other with different temporal and predictive relations. Autoshaping procedures overlay operant contingencies onto a classical-conditioning stimulus arrangement. In the present case, a neutral stimulus (a small gray square displayed on a touchscreen) functioned as the conditional stimulus and a food pellet functioned as the unconditional stimulus. Although touching is not required to produce food, with repeated stimulus pairings subjects eventually touch the stimulus. Across conditions of increasing stimulus correlation and temporal contiguity, male monkeys acquired the response faster with a moving stimulus. In contrast, females acquired the response faster with a stationary stimulus. These results demonstrate that the stimulus-movement effect may be differentially affected by sex and indicate that additional experiments with females are needed to determine how sex interacts with behavioral phenomena discovered and elaborated almost exclusively using males. Published by Elsevier Inc.

A longitudinal analysis of circulating stress-related proteins and chronic ethanol self-administration in cynomolgus macaques

PubMed Central

Helms, Christa M.; Messaoudi, Ilhem; Jeng, Sophia; Freeman, Willard M.; Vrana, Kent E.; Grant, Kathleen A.

2011-01-01

Background Alcoholics have alterations in endocrine and immune function and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates. Methods Plasma proteins (n = 60; Luminex) and hormones (adrenocorticotropic hormone, ACTH; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4 months and after 12 months of 22-h daily concurrent access to ethanol and water. Results Significant changes were observed in ACTH, cortisol and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, eight proteins were elevated and nine showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates. Conclusion Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity. PMID:22141444

Sertraline inhibits increases in body fat and carbohydrate dysregulation in adult female cynomolgus monkeys

PubMed Central

Silverstein-Metzler, Marnie G.; Shively, Carol A.; Clarkson, Thomas B.; Appt, Susan E.; Carr, J.Jeffrey; Kritchevsky, Stephen B.; Jones, Sara R.; Register, Thomas C.

2017-01-01

Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed for depression and other disorders. SSRIs have become one of the most commonly used drugs in the United States, particularly by women. Acute effects on body composition and carbohydrate metabolism have been reported, but little is known regarding the effects of chronic SSRI use. We evaluated the effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on body weight and composition, fat distribution, carbohydrate metabolism, as well as activity, in adult female depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n = 42) using a placebo-controlled, longitudinal, randomized study design. Phenotypes were evaluated prior to and after 18 months of oral sertraline (20 mg/kg) or placebo. Over the 18 month treatment period, the placebo group experienced increases in body weight, body fat (visceral and subcutaneous) fasting insulin concentrations, and homeostasis model assessment of insulin resistance scores (HOMA-IR). Sertraline treatment prevented increases in body weight, fat, insulin, and HOMA-IR (all p < 0.05), without significantly altering activity levels. Sertraline treatment altered adiponectin in an unusual way — reducing circulating adiponectin in depressed monkeys without affecting fat mass or body weight. Deleterious effects on adiponectin, a potentially insulin-sensitizing and atheroprotective protein, may result in adverse effects on cardiovascular health despite otherwise beneficial effects on body composition and carbohydrate metabolism. PMID:26939086

Network structure shapes spontaneous functional connectivity dynamics.

PubMed

Shen, Kelly; Hutchison, R Matthew; Bezgin, Gleb; Everling, Stefan; McIntosh, Anthony R

2015-04-08

The structural organization of the brain constrains the range of interactions between different regions and shapes ongoing information processing. Therefore, it is expected that large-scale dynamic functional connectivity (FC) patterns, a surrogate measure of coordination between brain regions, will be closely tied to the fiber pathways that form the underlying structural network. Here, we empirically examined the influence of network structure on FC dynamics by comparing resting-state FC (rsFC) obtained using BOLD-fMRI in macaques (Macaca fascicularis) to structural connectivity derived from macaque axonal tract tracing studies. Consistent with predictions from simulation studies, the correspondence between rsFC and structural connectivity increased as the sample duration increased. Regions with reciprocal structural connections showed the most stable rsFC across time. The data suggest that the transient nature of FC is in part dependent on direct underlying structural connections, but also that dynamic coordination can occur via polysynaptic pathways. Temporal stability was found to be dependent on structural topology, with functional connections within the rich-club core exhibiting the greatest stability over time. We discuss these findings in light of highly variable functional hubs. The results further elucidate how large-scale dynamic functional coordination exists within a fixed structural architecture. Copyright © 2015 the authors 0270-6474/15/355579-10$15.00/0.

Comparison of conventional and synchrotron-radiation-based microtomography of bone around dental implants

NASA Astrophysics Data System (ADS)

Cattaneo, Paolo M.; Dalstra, Michel; Beckmann, Felix; Donath, Tilman; Melsen, Birte

2004-10-01

This study explores the application of conventional micro tomography (μCT) and synchrotron radiation (SR) based μCT to evaluate the bone around titanium dental implants. The SR experiment was performed at beamline W2 of HASYLAB at DESY using a monochromatic X-ray beam of 50 keV. The testing material consisted of undecalcified bone segments harvested from the upper jaw of a macaca fascicularis monkey each containing a titanium dental implant. The results from the two different techniques were qualitatively compared with conventional histological sections examined under light microscopy. The SR-based μCT produced images that, especially at the bone-implant interface, are less noisy and sharper than the ones obtained with conventional μCT. For the proper evaluation of the implant-bone interface, only the SR-based μCT technique is able to display the areas of bony contact and visualize the true 3D structure of bone around dental implants correctly. This investigation shows that both conventional and SR-based μCT scanning techniques are non-destructive methods, which provide detailed images of bone. However with SR-based μCT it is possible to obtain an improved image quality of the bone surrounding dental implants, which display a level of detail comparable to histological sections. Therefore, SR-based μCT scanning could represent a valid, unbiased three-dimensional alternative to evaluate osseointegration of dental implants

An Automated Motion Detection and Reward System for Animal Training.

PubMed

Miller, Brad; Lim, Audrey N; Heidbreder, Arnold F; Black, Kevin J

2015-12-04

A variety of approaches has been used to minimize head movement during functional brain imaging studies in awake laboratory animals. Many laboratories expend substantial effort and time training animals to remain essentially motionless during such studies. We could not locate an "off-the-shelf" automated training system that suited our needs.  We developed a time- and labor-saving automated system to train animals to hold still for extended periods of time. The system uses a personal computer and modest external hardware to provide stimulus cues, monitor movement using commercial video surveillance components, and dispense rewards. A custom computer program automatically increases the motionless duration required for rewards based on performance during the training session but allows changes during sessions. This system was used to train cynomolgus monkeys (Macaca fascicularis) for awake neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The automated system saved the trainer substantial time, presented stimuli and rewards in a highly consistent manner, and automatically documented training sessions. We have limited data to prove the training system's success, drawn from the automated records during training sessions, but we believe others may find it useful. The system can be adapted to a range of behavioral training/recording activities for research or commercial applications, and the software is freely available for non-commercial use.

Information processing architecture of functionally defined clusters in the macaque cortex.

PubMed

Shen, Kelly; Bezgin, Gleb; Hutchison, R Matthew; Gati, Joseph S; Menon, Ravi S; Everling, Stefan; McIntosh, Anthony R

2012-11-28

Computational and empirical neuroimaging studies have suggested that the anatomical connections between brain regions primarily constrain their functional interactions. Given that the large-scale organization of functional networks is determined by the temporal relationships between brain regions, the structural limitations may extend to the global characteristics of functional networks. Here, we explored the extent to which the functional network community structure is determined by the underlying anatomical architecture. We directly compared macaque (Macaca fascicularis) functional connectivity (FC) assessed using spontaneous blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to directed anatomical connectivity derived from macaque axonal tract tracing studies. Consistent with previous reports, FC increased with increasing strength of anatomical connection, and FC was also present between regions that had no direct anatomical connection. We observed moderate similarity between the FC of each region and its anatomical connectivity. Notably, anatomical connectivity patterns, as described by structural motifs, were different within and across functional modules: partitioning of the functional network was supported by dense bidirectional anatomical connections within clusters and unidirectional connections between clusters. Together, our data directly demonstrate that the FC patterns observed in resting-state BOLD-fMRI are dictated by the underlying neuroanatomical architecture. Importantly, we show how this architecture contributes to the global organizational principles of both functional specialization and integration.

Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model

PubMed Central

Xie, Yilin; Su, Yingying; Tang, Jianxia; Goh, Bee Tin; Saigo, Leonardo; Zhang, Chunmei; Wang, Jinsong; Khojasteh, Arash; Wang, Songlin

2017-01-01

Antibody-mediated osseous regeneration (AMOR) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs) immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS) functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT) imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair. PMID:28401163

Ocular toxoplasmosis in immunosuppressed nonhuman primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holland, G.N.; O'Connor, G.R.; Diaz, R.F.

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 stimulatemore » 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.« less

Clinical and microbiological parameters of naturally occurring periodontitis in the non-human primate Macaca mulatta

PubMed Central

Colombo, A. P. V.; Paster, B. J.; Grimaldi, G.; Lourenço, T. G. B.; Teva, A.; Campos-Neto, A.; McCluskey, J.; Kleanthous, H.; Van Dyke, T. E.; Stashenko, P.

2017-01-01

ABSTRACT Background: Non-human primates appear to represent the most faithful model of human disease, but to date the oral microbiome in macaques has not been fully characterized using next-generation sequencing. Objective: In the present study, we characterized the clinical and microbiological features of naturally occurring periodontitis in non-human primates (Macaca mulatta). Design: Clinical parameters of periodontitis including probing pocket depth (PD) and bleeding on probing (BOP) were measured in 40 adult macaques (7–22 yrs), at six sites per tooth. Subgingival plaque was collected from diseased and healthy sites, and subjected to 16S rDNA sequencing and identification at the species or higher taxon level. Results: All macaques had mild periodontitis at minimum, with numerous sites of PD ≥ 4 mm and BOP. A subset (14/40) had moderate-severe disease, with >2 sites with PD ≥ 5mm, deeper mean PD, and more BOP. Animals with mild vs moderate-severe disease were identical in age, suggesting genetic heterogeneity. 16S rDNA sequencing revealed that all macaques had species that were identical to those in humans or closely related to human counterparts, including Porphyromonas gingivalis which was present in all animals. Diseased and healthy sites harboured distinct microbiomes; however there were no significant differences in the microbiomes in moderate-severe vs. mild periodontitis. Conclusions: Naturally occurring periodontitis in older macaques closely resembles human adult periodontitis, thus validating a useful model to evaluate novel anti-microbial therapies. PMID:29805776

Isolation, molecular cloning and in vitro expression of rhesus monkey (Macaca mulatta) prominin-1.s1 complementary DNA encoding a potential hematopoietic stem cell antigen.

PubMed

Husain, S M; Shou, Y; Sorrentino, B P; Handgretinger, R

2006-10-01

Human prominin-1 (CD133 or AC133) is an important cell surface marker used to isolate primitive hematopoietic stem cells. The commercially available antibody to human prominin-1 does not recognize rhesus prominin-1. Therefore, we isolated, cloned and characterized the complementary DNA (cDNA) of rhesus prominin-1 gene and determined its coding potential. Following the nomenclature of prominin family of genes, we named this cDNA as rhesus prominin-1.s1. The amino acid sequence data of the putative rhesus prominin-1.s1 could be used in designing antigenic peptides to raise antibodies for use in isolation of pure populations of rhesus prominin-1(+) hematopoietic cells. To the best of our knowledge, there has been no previously published report about the isolation of a prominin-1 cDNA from rhesus monkey (Macaca mulatta).

Using biological markets principles to examine patterns of grooming exchange in Macaca thibetana.

PubMed

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. © 2011 Wiley Periodicals

Do Tonkean macaques (Macaca tonkeana) perceive what conspecifics do and do not see?

PubMed Central

Piraux, Emilie; Poulin, Nicolas; Meunier, Hélène

2016-01-01

The understanding of the visual perception of others, also named visual perspective taking, is a component of Theory of Mind. Although strong evidence of visual perspective taking has been reported in great apes, the issue is more open to discussion in monkeys. We investigated whether Tonkean macaques (Macaca tonkeana) know what conspecifics do and do not see, using a food competition paradigm originally developed in great apes. We tested individuals in pairs, after establishing the dominance relationship within each pair. Twenty-one pairs were tested in four different conditions. In one condition, the subordinate had the choice between two pieces of food, one that was visible only to it and another that was also visible to the dominant. It was predicted that if the subordinate understands that the dominant cannot see both pieces of food because one is hidden from its view, the subordinate should preferentially go for the food visible only to itself. In the three other conditions, we varied the temporal and visual access to food for both individuals, to control for alternative explanations based on dominance. We recorded the first movement direction chosen by subjects, i.e. towards a) visible food b) hidden food or c) elsewhere; and the outcome of the test, i.e. the quantity of food obtained. Results showed that subordinates moved preferentially for the hidden food when released simultaneously with the dominant and also with a head start on the dominant. By contrast, dominants’ choices of the two pieces of food were random. We also describe and discuss some of the strategies used by subordinates in these tests. According to the whole of our results, Tonkean macaques seem capable of visual perspective taking despite the fact that a low-level explanation as behavior reading has not been totally excluded. PMID:26925323

Sex Differences in the Development of Social Relationships in Rhesus Macaques (Macaca mulatta).

PubMed

Kulik, Lars; Amici, Federica; Langos, Doreen; Widdig, Anja

2015-04-01

Several studies have documented the importance of social bonding for the enhancement of individual fitness. However, little is known about how social relationships develop through ontogeny, and whether their development follows the same trajectory in males and females. Here we analyzed affiliative interactions (proximity, social grooming, play) combined with demographic and genetic data in semi-free-ranging rhesus macaques ( Macaca mulatta ) on Cayo Santiago over their first 4 yr of life (from birth to sexual maturation) to understand how these interactions change through development in both sexes. Generalized linear mixed models revealed that social behaviors mostly followed different developmental trajectories in males and females and were highly dependent on the social context. In particular, sex differences in social behavior varied through development depending on the partner's sex and age. Females engaged in more social interactions than males, especially with other females, and were more involved in grooming around the time of maturation. In contrast, males interacted more with males and age peers, especially around maturation. Sex differences in social behavior varied through development, but also depended on rank, partner's rank, and kin line, although not consistently. High-ranking individuals, especially older females, were generally preferred as social partners. Moreover, both male and female individuals interacted mostly with maternal kin, although males also preferred paternal kin over nonkin. Importantly, most developmental changes in sociality happened when individuals were ca . 2 yr old, suggesting that this might be a milestone in the development of sociality in rhesus macaques. The only notable exception to this pattern was play, which was more pronounced in males from the beginning of their lives. We propose that play might serve as a trigger of sex differences in social behavior, with sex differences emerging early in development and increasing

Rhesus monkeys (Macaca mulatta) detect rhythmic groups in music, but not the beat.

PubMed

Honing, Henkjan; Merchant, Hugo; Háden, Gábor P; Prado, Luis; Bartolo, Ramón

2012-01-01

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).

What Meaning Means for Same and Different: Analogical Reasoning in Humans (Homo sapiens), Chimpanzees (Pan troglodytes), and Rhesus Monkeys (Macaca mulatta)

PubMed Central

Flemming, Timothy M.; Beran, Michael J.; Thompson, Roger K. R.; Kleider, Heather M.; Washburn, David A.

2013-01-01

Thus far, language- and token-trained apes (e.g., D. Premack, 1976; R. K. R. Thompson, D. L. Oden, & S. T. Boysen, 1997) have provided the best evidence that nonhuman animals can solve, complete, and construct analogies, thus implicating symbolic representation as the mechanism enabling the phenomenon. In this study, the authors examined the role of stimulus meaning in the analogical reasoning abilities of three different primate species. Humans (Homo sapiens), chimpanzees (Pan troglodytes), and rhesus monkeys (Macaca mulatta) completed the same relational matching-to-sample (RMTS) tasks with both meaningful and nonmeaningful stimuli. This discrimination of relations-between-relations serves as the basis for analogical reasoning. Meaningfulness facilitated the acquisition of analogical matching for human participants, whereas individual differences among the chimpanzees suggest that meaning can either enable or hinder their ability to complete analogies. Rhesus monkeys did not succeed in the RMTS task regardless of stimulus meaning, suggesting that their ability to reason analogically, if present at all, may be dependent on a dimension other than the representational value of stimuli. PMID:18489233

Evaluation of a therapy for Idiopathic Chronic Enterocolitis in rhesus macaques (Macaca mulatta) and linked microbial community correlates

PubMed Central

Baker, Kate; Lauder, Abigail; Kim, Dorothy; Bailey, Aubrey; Wu, Gary D.; Collman, Ronald G.; Doyle-Meyers, Lara; Russell-Lodrigue, Kasi; Blanchard, James; Bushman, Frederic D.; Bohm, Rudolf

2018-01-01

Idiopathic chronic enterocolitis (ICE) is one of the most commonly encountered and difficult to manage diseases of captive rhesus macaques (Macaca mulatta). The etiology is not well understood, but perturbations in gut microbial communities have been implicated. Here we evaluated the effects of a 14-day course of vancomycin, neomycin, and fluconazole on animals affected with ICE, comparing treated, untreated, and healthy animals. We performed microbiome analysis on duodenal and colonic mucosal samples and feces in order to probe bacterial and/or fungal taxa potentially associated with ICE. All treated animals showed a significant and long-lasting improvement in stool consistency over time when compared to untreated and healthy controls. Microbiome analysis revealed trends associating bacterial community composition with ICE, particularly lineages of the Lactobacillaceae family. Sequencing of DNA from macaque food biscuits revealed that fungal sequences recovered from stool were dominated by yeast-derived food additives; in contrast, bacteria in stool appeared to be authentic gut residents. In conclusion, while validation in larger cohorts is needed, the treatment described here was associated with significantly improved clinical signs; results suggested possible correlates of microbiome structure with disease, though no strong associations were detected between single microbes and ICE. PMID:29666764

Beneficial Use of Dredged Material Monitoring Program. 1996 Annual report (Base Year Through Fy1996).

DTIC Science & Technology

1997-01-01

Echinochloa walteri _ Panicum dichotomiflorum _ Leptochloa fascicularis Cynodon dactylon Paspalum distichum Suaeda linearis Xanthium strumarium ...fascicularis Cynodon dactylon Paspalum distichum Salicornia bigelovii Atriplex pentandra Suaeda linearis Conyza canadensis Xanthium strumarium ...marshes, low fields Xanthium strumarium L cocklebur annual; waste places, old fields, pond shores, ditches, stable dune areas, beaches 5A-6 U.S

Sagittal Plane Kinematics of the Jaw and Hyolingual Apparatus During Swallowing in Macaca mulatta

PubMed Central

Iriarte-Diaz, Jose; Arce-McShane, Fritzie; Orsbon, Courtney P.; Brown, Kevin A.; Eastment, McKenna; Avivi-Arber, Limor; Sessle, Barry J.; Inoue, Makoto; Hatsopoulos, Nicholas G.; Ross, Callum F.

2018-01-01

Studies of mechanisms of feeding behavior are important in a society where aging- and disease-related feeding disorders are increasingly prevalent. It is important to evaluate the clinical relevance of animal models of the disease and the control. Our present study quantifies macaque hyolingual and jaw kinematics around swallowing cycles to determine the extent to which macaque swallowing resembles that of humans. One female and one male adult Macaca mulatta were trained to feed in a primate chair. Videofluoroscopy was used to record kinematics in a sagittal view during natural feeding on solid food, and the kinematics of the hyoid bone, thyroid cartilage, mandibular jaw, and anterior-, middle-, and posterior-tongue. Jaw gape cycles were defined by consecutive maximum gapes, and the kinematics of the swallow cycles were compared with those of the two consecutive non-swallow cycles preceding and succeeding the swallow cycles. Although there are size differences between macaques and humans, and macaques have shorter durations of jaw gape cycles and hyoid and thyroid upward movements, there are several important similarities between our macaque data and human data reported in the literature: (1) The durations of jaw gape cycles during swallow cycles are longer than those of non-swallow cycles as a result of an increased duration of the jaw-opening phase; (2) Hyoid and thyroid upward movement is linked with a posterior tongue movement and is faster during swallow than non-swallow cycles; (3) Tongue elevation propagates from anterior to posterior during swallow and non-swallow cycles. These findings suggest that macaques can be a useful experimental model for human swallowing studies. PMID:28528492

Speech-like orofacial oscillations in stump-tailed macaque (Macaca arctoides) facial and vocal signals.

PubMed

Toyoda, Aru; Maruhashi, Tamaki; Malaivijitnond, Suchinda; Koda, Hiroki

2017-10-01

Speech is unique to humans and characterized by facial actions of ∼5 Hz oscillations of lip, mouth or jaw movements. Lip-smacking, a facial display of primates characterized by oscillatory actions involving the vertical opening and closing of the jaw and lips, exhibits stable 5-Hz oscillation patterns, matching that of speech, suggesting that lip-smacking is a precursor of speech. We tested if facial or vocal actions exhibiting the same rate of oscillation are found in wide forms of facial or vocal displays in various social contexts, exhibiting diversity among species. We observed facial and vocal actions of wild stump-tailed macaques (Macaca arctoides), and selected video clips including facial displays (teeth chattering; TC), panting calls, and feeding. Ten open-to-open mouth durations during TC and feeding and five amplitude peak-to-peak durations in panting were analyzed. Facial display (TC) and vocalization (panting) oscillated within 5.74 ± 1.19 and 6.71 ± 2.91 Hz, respectively, similar to the reported lip-smacking of long-tailed macaques and the speech of humans. These results indicated a common mechanism for the central pattern generator underlying orofacial movements, which would evolve to speech. Similar oscillations in panting, which evolved from different muscular control than the orofacial action, suggested the sensory foundations for perceptual saliency particular to 5-Hz rhythms in macaques. This supports the pre-adaptation hypothesis of speech evolution, which states a central pattern generator for 5-Hz facial oscillation and perceptual background tuned to 5-Hz actions existed in common ancestors of macaques and humans, before the emergence of speech. © 2017 Wiley Periodicals, Inc.

Diversity and Molecular Phylogeny of Mitochondrial DNA of Rhesus Macaques (Macaca mulatta) in Bangladesh

PubMed Central

HASAN, M. KAMRUL; FEEROZ, M. MOSTAFA; JONES-ENGEL, LISA; ENGEL, GREGORY A.; KANTHASWAMY, SREE; SMITH, DAVID GLENN

2015-01-01

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. PMID:24810278

Disability, compensatory behavior, and innovation in free-ranging adult female Japanese macaques (Macaca fuscata).

PubMed

Turner, Sarah E; Fedigan, Linda M; Matthews, H Damon; Nakamichi, Masayuki

2012-09-01

Little is known about consequences of disability in nonhuman primates, yet individuals with disabilities can reveal much about behavioral flexibility, innovation, and the capabilities of a species. The Macaca fuscata population surrounding the Awajishima Monkey Center has experienced high rates of congenital limb malformation for at least 40 years, creating a unique opportunity to examine consequences of physical impairment in situ, in a relatively large sample of free-ranging adult monkeys. Here we present behavioral data on 11 disabled adult females and 12 nondisabled controls from 279 hours of randomly ordered 30-minute focal animal follows collected during May-August in 2005, 2006, and 2007. We quantified numerous statistically significant disability-related behavioral differences among females. Disabled females spent less time begging for peanuts from tourists, and employed a behavioral variant of such peanut begging; they had a lower frequency of hand use in grooming and compensated with increased direct use of the mouth or a two-arm pinch technique; and they had a higher frequency of self-scratching, and more use of feet in self-scratching. Self-scratching against substrates was almost exclusively a disability associated behavior. Two females used habitual bipedalism. These differences not withstanding, disabled females behaved similarly to controls in many respects: overall reliance on provisioned and wild foods, time spent feeding, and feeding efficiency did not differ among females, and there was no time difference in behavior performed arboreally or terrestrially. Disabled adult females were able to compensate behaviorally to perform social and life-sustaining activities, modifying existing behaviors to suit their individual physical situations and, occasionally, inventing new ways of doing things. © 2012 Wiley Periodicals, Inc.

Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

PubMed

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.

Stimulus-Food Pairings Produce Stimulus-Directed Touch-Screen Responding in Cynomolgus Monkeys (MACACA Fascicularis) With or Without a Positive Response Contingency

DTIC Science & Technology

2009-07-01

REPORT NUMBER US Army Medical Research Institute of Chemical Defense ATTN: MCMR-CDT-N 3100 Ricketts Point Road Aberdeen Proving Ground, MD...Medical Research Institute of Chemical Defense Aberdeen Proving Ground, MD 21010-5400 ATTN: MCMR-CDZ-I 11. SPONSOR/MONITOR’S REPORT 3100 Ricketts...CONTINGENCY CHRISTOPHER E. BULLOCK AND TODD M. MYERS UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE Acquisition and maintenance of

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

PubMed

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.

Enoxaparin Treatment of Spontaneous Deep Vein Thrombosis in a Chronically Catheterized Rhesus Macaque (Macaca mulatta)

PubMed Central

Wathen, Asheley B; Myers, Daniel D; Zajkowski, Paul; Flory, Graham; Hankenson, F Claire

2009-01-01

A chronically catheterized 14-y-old male rhesus macaque (Macaca mulatta) was reported for recurrent scrotal swelling. The scrotum was enlarged and warm to touch, and associated skin was noted to be lichenified on physical examination. The penis could not be extruded due to preputial swelling. Results from the following diagnostic tests were all unremarkable or within normal limits: scrotal aspirate, hematology, serum biochemistries, urinalysis, and radiography of the thorax, scrotum, and abdomen. Ultrasonography of lower extremities identified thrombi in bilateral iliac veins and left femoral vein. Collateral circulation surrounding the left femoral vein permitted some compensatory venous return. The left femoral vein of this animal had been catheterized approximately 2 mo before initial presentation. A coagulation panel revealed a positive D-dimer test, indicative of elevated levels of fibrin degradation products due to active thrombus breakdown. Enoxaparin sodium, a low-molecular-weight heparin for human use, was administered at 20 mg subcutaneously once daily for 10 d to treat occlusive venous thrombi. After enoxaparin treatment, the edema was greatly decreased. To achieve complete resolution, a second course of enoxaparin was administered 2 months after the first. Ultrasonography of the pelvic vasculature 6 mo after completion of therapy showed marked thrombus resolution, allowing for bilateral patency in the iliac and femoral veins. Follow-up evaluation revealed that D-dimer values were negative as well. This case demonstrates the novel application of the human medication enoxaparin to treat clinical signs of deep vein thrombosis in a chronically catheterized rhesus macaque. PMID:19807974

Methemoglobin and sulfhemoglobin formation due to benzocaine and lidocaine in macaques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, D.G.; Woodard, C.L.; Gold, M.B.

1993-05-13

Benzocaine (BNZ) and lidocaine (LC) are commonly used topical (spray) anesthetics approved for use in humans. BNZ has structural similarities to methemoglobin (MHb) forming drugs that are current candidates for cyanide prophylaxis, while LC has been reported to increase MHb in man. We therefore, compared MHb and sulfhemoglobin (SHb) production in three groups of Macaques (Macaca mulata, Chinese rhesus and Indian rhesus, and Macaca nemistrina, Pig-tailed Macaques) after exposure to BNZ and LC. Formation of SHb, unlike MHb, is not thought to be reversible and is considered to be toxic. MHb and SHb levels were measured periodically on a CO-Oximeter.more » All rhesus (n=8) were dosed intratrachealy/intranasaly with 56 mg and 280 mg BNZ and with 40 mg of LC in a randomized cross-over design. Pig-tailed macaques (n=6) were dosed with BNZ intranasaly 56 mg and with 40 mg of LC. Since no differences in the peak MHb or time to peak (mean +/- SD) were observed among the three macaque subspecies, the data were pooled. LC did not cause MHb or SHb formation above baseline in any monkey.« less

Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata).

PubMed

Ravindranath, N; Ramesh, V; Krishnamurthy, H N; Rao, A J; Moudgal, R N

1992-03-01

To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). Proven fertile male monkeys exhibiting normal testicular function. Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

Absolute auditory thresholds in three Old World monkey species (Cercopithecus aethiops, C. neglectus, Macaca fuscata) and humans (Homo sapiens).

PubMed

Owren, M J; Hopp, S L; Sinnott, J M; Petersen, M R

1988-06-01

We investigated the absolute auditory sensitivities of three monkey species (Cercopithecus aethiops, C. neglectus, and Macaca fuscata) and humans (Homo sapiens). Results indicated that species-typical variation exists in these primates. Vervets, which have the smallest interaural distance of the species that we tested, exhibited the greatest high-frequency sensitivity. This result is consistent with Masterton, Heffner, and Ravizza's (1969) observations that head size and high-frequency acuity are inversely correlated in mammals. Vervets were also the most sensitive in the middle frequency range. Furthermore, we found that de Brazza's monkeys, though they produce a specialized, low-pitched boom call, did not show the enhanced low-frequency sensitivity that Brown and Waser (1984) showed for blue monkeys (C. mitis), a species with a similar sound. This discrepancy may be related to differences in the acoustics of the respective habitats of these animals or in the way their boom calls are used. The acuity of Japanese monkeys was found to closely resemble that of rhesus macaques (M. mulatta) that were tested in previous studies. Finally, humans tested in the same apparatus exhibited normative sensitivities. These subjects responded more readily to low frequencies than did the monkeys but rapidly became less sensitive in the high ranges.

Trauma rates and patterns in specific pathogen free (SPF) rhesus macaque (Macaca mulatta) groups.

PubMed

Stavisky, Ronda C; Ramsey, Jacklyn K; Meeker, Tracy; Stovall, Melissa; Crane, Maria M

2018-03-01

There are some predictable patterns of trauma in captive rhesus macaque (Macaca mulatta) social groups. Several factors have been documented to contribute to these patterns, including group formation of unrelated animals, and the establishment of dominance ranks. Here, we report on how socially induced trauma in groups of rhesus monkeys is influenced by the breeding season, numbers of matrilines per group and matriline size. We analyzed 3 years of data collected from veterinary admittance logs for four groups in our specific pathogen free (SPF) breeding colony. Since the groups differed in time from formation, both the numbers of matrilines and the composition of those matrilines were different. Across the four groups, trauma rates were significantly higher during the fall breeding season than the spring and summer months when births occur. The group that was formed most recently, comprised of the greatest number of matrilines but fewest related animals, showed significantly higher rates of trauma than the older social groups. Further, the middle and lowest ranking families received signifincantly higher rates of trauma than the highest ranking families, suggesting a rank-related phenomenon. Additionally, there was a significant negative correlation between numbers of adult females in a matriline and rates of trauma observed in each matriline, but the numbers of adult females are significantly higher in the top ranked families compared to all of the other matrilines. These findings suggest that trauma rates increase during the breeding season and may be exacerbated in recently formed breeding groups that have smaller matrilines and reduced opportunities for social support to mitigate rank-related aggression. Management practices should be devised to ensure adequate matrilineal size to decrease rates of trauma in captive rhesus macaque groups. © 2018 Wiley Periodicals, Inc.

Diversity and molecular phylogeny of mitochondrial DNA of rhesus macaques (Macaca mulatta) in Bangladesh.

PubMed

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. © 2014 Wiley Periodicals, Inc.

Abdominal Lipomatosis with Secondary Self-Strangulation of Masses in an Adult Rhesus Macaque (Macaca mulatta)

PubMed Central

Chum, Helen H; Long, C Tyler; McKeon, Gabriel P; Chang, Angela G; Luong, Richard H; Albertelli, Megan A

2014-01-01

An 10-y-old, intact male rhesus macaque (Macaca mulatta) presented for bilateral scrotal swelling and a distended abdomen. A soft mass in the left upper quadrant of the abdomen was palpated. A barium study did not reveal any gastrointestinal abnormalities. Exploratory laparotomy revealed a large (1.25 kg, 15.0 × 13.0 × 9.5 cm), red and tan, soft, circumscribed, spherical mass within the greater omentum and 10 to 20 smaller (diameter, 1 to 4 cm), soft to firm masses in the mesentery and greater omentum. The resected mass was a self-strangulating abdominal lipoma, a pedunculated neoplasm composed of white adipocytes arising from peritoneal adipose tissue undergoing secondary coagulation necrosis after strangulation of the blood supply due to twisting of the mass around the peduncle. The smaller masses were histologically consistent with simple or self-strangulating pedunculated abdominal lipomas. The macaque presented again 9 mo later with a firm, 5.0-cm mass in the midabdomen, with intestinal displacement visible on radiographs. Given this animal's medical history and questionable prognosis, euthanasia was elected. Necropsy revealed numerous, multifocal to coalescing, 1.0- to 15.0-cm, pale tan to yellow, circumscribed, soft to firm, spherical to ellipsoid, pedunculated masses that were scattered throughout the mesentery, greater omentum, lesser omentum, and serosal surfaces of the gastrointestinal tract. All of the masses were pedunculated abdominal lipomas, and most demonstrated coagulation necrosis due to self-strangulation of the blood supply. To our knowledge, this report is the first to describe abdominal lipomatosis with secondary self-strangulation of masses in a rhesus macaque. PMID:25402181

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

PubMed Central

Dettmer, Amanda M.; 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 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 showed less of a stress response, spending less time near their surrogates in the first five minutes of the test session than RS infants (p=.05) and exhibiting a significantly lower rise in salivary cortisol after the test than RS infants (p=.018). 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. PMID:19810188

Immunophenotypic Alterations in Resident Immune Cells and Myocardial Fibrosis in the Aging Rhesus Macaque (Macaca mulatta) Heart

PubMed Central

Macri, Sheila C.; Bailey, Charles C.; de Oca, Nicole Monts; Silva, Nilsa A.; Rosene, Douglas L.; Mansfield, Keith G.; Miller, Andrew D.

2012-01-01

The rhesus macaque (Macaca mulatta) is used extensively in translational biomedical research and drug development studies and is an important model of aging. Macaques often develop myocardial fibrosis with age which can result in the loss of normal cardiac architecture with the expansion of the extracellular matrix and deposition of collagen. The etiology and pathogenesis of this pernicious process is poorly understood. Cardiac fibrosis was assessed using histologic and immunohistochemical techniques in cardiac tissue sections from 34 rhesus macaques. Overall left ventricular and left ventricular mid-myocardial interstitial/perivascular fibrosis were positively correlated with age (r=0.6522, p<0.0001 and r=0.4704, p=0.005, respectively). When divided into young (mean=2.8 years), middle-aged (mean=17.5 years), and advanced age (mean=29.2 years) groups, immunophenotypic characterization of antigen presenting cells revealed differential expression of CD163 and DC-SIGN between the young and middle-aged groups compared to the advanced age group (p<0.0001). HAM-56 expression decreased significantly in the advanced age cohort (p=0.0021). The expression of CD8, CD163, and DCSIGN correlated positively with age (r=0.3999, p= 0.0191; r=0.5676, p=0.0005; r=0.5245, p=0.0014 respectively). These results show the importance of myocardial fibrosis as a common age-related pathology and additionally, alterations in T cell, macrophage, and dendritic cell phenotype in rhesus macaque myocardium are associated with age but unassociated with the fibrosis. PMID:22328408

Minimally Invasive Lumbar Port System for the Collection of Cerebrospinal Fluid from Rhesus Macaques (Macaca mulatta)

PubMed Central

MacAllister, Rhonda Pung; Lester McCully, Cynthia M; Bacher, John; Thomas, Marvin L; Cruz, Rafael; Wangari, Solomon; Warren, Katherine E

2016-01-01

Biomedical translational research frequently incorporates collection of CSF from NHP, because CSF drug levels are used as a surrogate for CNS tissue penetration in pharmacokinetic and dynamic studies. Surgical placement of a CNS ventricular catheter reservoir for CSF collection is an intensive model to create and maintain and thus may not be feasible or practical for short-term studies. Furthermore, previous NHP lumbar port models require laminectomy for catheter placement. The new model uses a minimally invasive technique for percutaneous placement of a lumbar catheter to create a closed, subcutaneous system for effective, repeated CSF sample collection. None of the rhesus macaques (Macaca mulatta; n = 10) implanted with our minimally invasive lumbar port (MILP) system experienced neurologic deficits, postoperative infection of the surgical site, or skin erosion around the port throughout the 21.7-mo study. Functional MILP systems were maintained in 70% of the macaques, with multiple, high-quality, 0.5- to 1.0-mL samples of CSF collected for an average of 3 mo by using aspiration or gravitational flow. Among these macaques, 57% had continuous functionality for a mean of 19.2 mo; 50% of the cohort required surgical repair for port repositioning and replacement during the study. The MILP was unsuccessful in 2 macaques, at an average of 9.5 d after surgery. Nonpatency in these animals was attributed to the position of the lumbar catheter. The MILP system is an appropriate replacement for temporary catheterization and previous models requiring laminectomy and is a short-term alternative for ventricular CSF collection systems in NHP. PMID:27538866

Conceptual thresholds for same and different in old-(Macaca mulatta) and new-world (Cebus apella) monkeys

PubMed Central

Flemming, Timothy M.

2011-01-01

Learning of the relational same/different (S/D) concept has been demonstrated to be largely dependent upon stimulus sets containing more than two items for pigeons and old-world monkeys. Stimulus arrays containing several images for use in same/different discrimination procures (e.g. 16 identical images vs. 16 nonidentical images) have been shown to facilitate and even be necessary for learning of relational concepts (Flemming, Beran & Washburn, 2007; Wasserman, Young & Fagot, 2001; Young, Wasserman & Garner, 1997). In the present study, we investigate the threshold at which a new world primate, the capuchin (Cebus apella) may be able to make such a discrimination. Utilizing a method of increasing entropy, rather than conventional procedures of decreasing entropy, we demonstrate unique evidence that capuchin monkeys are readily capable of making 2-item relational S/D conditional discriminations. In another experiment, we examine the supposed level of difficulty in making S/D discriminations by rhesus monkeys (Macaca mulatta). Whereas pigeons (Columba livia) and baboons (Papio papio) have shown marked difficulty simultaneously discriminating same from different arrays at all when composed of fewer than 8 items each, rhesus monkeys seem to understand that pairs of stimuli connote sameness and difference just the same (Flemming et al., 2007). With sustained accurate performance of 2-item S/D discriminations, both experienced and task-naïve rhesus monkeys appear quite certain in their conceptual knowledge of same and different. We conclude that learning of the same/different relational concept may be less dependent upon high levels of entropy contrast than originally hypothesized for nonhuman primates. PMID:21238555

Palisade endings in extraocular muscles of the monkey are immunoreactive for choline acetyltransferase and vesicular acetylcholine transporter.

PubMed

Konakci, Kadriye Zeynep; Streicher, Johannes; Hoetzenecker, Wolfram; Haberl, Ines; Blumer, Michael Josef Franz; Wieczorek, Grazyna; Meingassner, Josef Gottfried; Paal, Szabolcs Levente; Holzinger, Daniel; Lukas, Julius-Robert; Blumer, Roland

2005-12-01

To analyze palisade endings in extraocular muscles (EOMs) of a primate species and to examine our previous findings in cat that palisade endings are putative effector organs. Eleven monkeys (Macaca fascicularis) of both sexes, between 4 and 6 years of age were analyzed. Whole EOM myotendons were immunostained with four combinations of triple-fluorescent labeling and examined by confocal laser scanning microscopy. Labeling included antibodies against choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), neurofilament, and synaptophysin. Muscle fibers were counterstained with phalloidin. Palisade endings were observed in all monkey EOMs. Nerve fibers extended from the muscle into the tendon and looped back to divide into a terminal arborization (palisade ending) around a single muscle fiber tip. In approximately 30% of the cases, nerve fibers supplying palisade endings often established motor terminals outside the palisade complex. Nerve fibers forming palisade endings were ChAT-neurofilament positive. Axonal branches of palisade endings were ChAT-neurofilament positive as well. All palisade nerve terminals exhibited ChAT-synaptophysin immunoreactivity. Within the palisade complex, palisade nerve terminals exhibited VAChT immunoreactivity. All palisade nerve terminals were VAChT-synaptophysin immunoreactive. The results confirm that in the monkey, palisade endings contain acetylcholine and are therefore most likely effector organs. Palisade endings are also present in human EOMs and because of their location at the myotendinous junction, these organs are of crucial interest for strabismus surgery.

Characterization of Cerebral Damage in a Monkey Model of Alzheimer's Disease Induced by Intracerebroventricular Injection of Streptozotocin.

PubMed

Yeo, Hyeon-Gu; Lee, Youngjeon; Jeon, Chang-Yeop; Jeong, Kang-Jin; Jin, Yeung Bae; Kang, Philyong; Kim, Sun-Uk; Kim, Ji-Su; Huh, Jae-Won; Kim, Young-Hyun; Sim, Bo-Woong; Song, Bong-Seok; Park, Young-Ho; Hong, Yonggeun; Lee, Sang-Rae; Chang, Kyu-Tae

2015-01-01

In line with recent findings showing Alzheimer's disease (AD) as an insulin-resistant brain state, a non-transgenic animal model with intracerebroventricular streptozotocin (icv-STZ) administration has been proposed as a representative experimental model of AD. Although icv-STZ rodent models of AD have been increasingly researched, studies in non-human primate models are very limited. In this study, we aimed to characterize the cerebral damage caused by icv-STZ in non-human primates; to achieve this, three cynomolgus monkeys (Macaca fascicularis) were administered four dosages of STZ (2 mg/kg) dissolved in artificial cerebrospinal fluid and another three controls were injected with only artificial cerebrospinal fluid at the cerebellomedullary cistern. In vivo neuroimaging was performed with clinical 3.0 T MRI, followed by quantitative analysis with FSL for evaluation of structural changes of the brain. Immunohistochemistry was performed to evaluate cerebral histopathology. We showed that icv-STZ caused severe ventricular enlargement and parenchymal atrophy, accompanying amyloid-β deposition, hippocampal cell loss, tauopathy, ependymal cell loss, astrogliosis, and microglial activation, which are observed in human aged or AD brain. The findings suggest that the icv-STZ monkey model would be a valuable resource to study the mechanisms and consequences of a variety of cerebral pathologies including major pathological hallmarks of AD. Furthermore, the study of icv-STZ monkeys could contribute to the development of treatments for age- or AD-associated cerebral changes.

Force-related neuronal activity in two regions of the primate ventral premotor cortex.

PubMed

Hepp-Reymond, M C; Hüsler, E J; Maier, M A; Ql, H X

1994-05-01

Neuronal activity was recorded in the ventral premotor cortex of one monkey (Macaca fascicularis) trained to exert finely graded forces with thumb and index finger on a force sensor in a visuomotor step-tracking paradigm. Trials with two or three consecutive ramp-and-hold force steps were presented randomly. Most neurons displayed similar discharge patterns in the two- and three-step trials and were assigned to one of the following classes: phasic, phasic-tonic, tonic, decreasing, and mixed. For more than 50% of the neurons with tonic activity, positive or negative correlations between firing rate and force were statistically significant. The indices of force sensitivity were on average higher for the two-step than for the three-step trials, indicating that the correlations yielded linearity over only a limited force range. The force-related cells were located in two regions of the ventral premotor cortex. One group was ying rostrally within the inferior limb of the arcuate sulcus, from which microstimulation elicited movements of fingers and hand. In the other more caudal region, adjacent to the finger region of primary motor cortex, microstimulation was rarely effective, but all neurons had clear peripheral receptive fields on finger and hand. The data indicate that two populations of neurons, located in the ventral premotor cortex, are related to movement execution. Effective microstimulation also suggests that one of the populations has fairly direct access to the spinal motor apparatus.

Longitudinal changes in reproductive hormones and menstrual cyclicity in cynomolgus monkeys during strenuous exercise training: abrupt transition to exercise-induced amenorrhea.

PubMed

Williams, N I; Caston-Balderrama, A L; Helmreich, D L; Parfitt, D B; Nosbisch, C; Cameron, J L

2001-06-01

Cross-sectional studies of exercise-induced reproductive dysfunction have documented a high proportion of menstrual cycle disturbances in women involved in strenuous exercise training. However, longitudinal studies have been needed to examine individual susceptibility to exercise-induced reproductive dysfunction and to elucidate the progression of changes in reproductive function that occur with strenuous exercise training. Using the female cynomolgus monkey (Macaca fascicularis), we documented changes in menstrual cyclicity and patterns of LH, FSH, estradiol, and progesterone secretion as the animals developed exercise-induced amenorrhea. As monkeys gradually increased running to 12.3 +/- 0.9 km/day, body weight did not change significantly although food intake remained constant. The time spent training until amenorrhea developed varied widely among animals (7-24 months; mean = 14.3 +/- 2.2 months) and was not correlated with initial body weight, training distance, or food intake. Consistent changes in function of the reproductive axis occurred abruptly, one to two menstrual cycles before the development of amenorrhea. These included significant declines in plasma reproductive hormone concentrations, an increase in follicular phase length, and a decrease in luteal phase progesterone secretion. These data document a high level of interindividual variability in the development of exercise-induced reproductive dysfunction, delineate the progression of changes in reproductive hormone secretion that occur with exercise training, and illustrate an abrupt transition from normal cyclicity to an amenorrheic state in exercising individuals, that is not necessarily associated with weight loss.

NKp44 expression, phylogenesis and function in non-human primate NK cells

PubMed Central

De Maria, Andrea; Ugolotti, Elisabetta; Rutjens, Erik; Mazza, Stefania; Radic, Luana; Faravelli, Alessandro; Koopman, Gerrit; Di Marco, Eddi; Costa, Paola; Ensoli, Barbara; Cafaro, Aurelio; Mingari, Maria Cristina; Moretta, Lorenzo; Heeney, Jonathan

2009-01-01

Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in species other than Homo sapiens has been elusive, so far. Here, we provide complete phenotypic, molecular and functional characterization for NKp44 triggering receptor on Pan troglodytes NK cells, the closest human relative, and the analysis of NKp44-genomic locus and transcription in Macaca fascicularis. Similar to H. sapiens, NKp44 expression is detectable on chimpanzee NK cells only upon activation. However, basal NKp44 transcription is 5-fold higher in chimpanzees with lower differential increases upon cell activation compared with humans. Upon activation, an overall 12-fold lower NKp44 gene expression is observed in P. troglodytes compared with H. sapiens NK cells with only a slight reduction in NKp44 surface expression. Functional analysis of ‘in vitro’ activated purified NK cells confirms the NKp44 triggering potential compared with other major NCRs. These findings suggest the presence of a post-transcriptional regulation that evolved differently in H. sapiens. Analysis of cynomolgus NKp44-genomic sequence and transcription pattern showed very low levels of transcription with occurrence of out-of-frame transcripts and no surface expression. The present comparative analysis suggests that NKp44-genomic organization appears during macaque speciation, with considerable evolution of its transcriptional and post-transcriptional tuning. Thus, NKp44 may represent an NCR being only recently emerged during speciation, acquiring functional relevance only in non-human primates closest to H. sapiens. PMID:19147838

Thalamic projections to visual and visuomotor areas (V6 and V6A) in the Rostral Bank of the parieto-occipital sulcus of the Macaque.

PubMed

Gamberini, Michela; Bakola, Sophia; Passarelli, Lauretta; Burman, Kathleen J; Rosa, Marcello G P; Fattori, Patrizia; Galletti, Claudio

2016-04-01

The medial posterior parietal cortex of the primate brain includes different functional areas, which have been defined based on the functional properties, cyto- and myeloarchitectural criteria, and cortico-cortical connections. Here, we describe the thalamic projections to two of these areas (V6 and V6A), based on 14 retrograde neuronal tracer injections in 11 hemispheres of 9 Macaca fascicularis. The injections were placed either by direct visualisation or using electrophysiological guidance, and the location of injection sites was determined post mortem based on cyto- and myeloarchitectural criteria. We found that the majority of the thalamic afferents to the visual area V6 originate in subdivisions of the lateral and inferior pulvinar nuclei, with weaker inputs originating from the central densocellular, paracentral, lateral posterior, lateral geniculate, ventral anterior and mediodorsal nuclei. In contrast, injections in both the dorsal and ventral parts of the visuomotor area V6A revealed strong inputs from the lateral posterior and medial pulvinar nuclei, as well as smaller inputs from the ventrolateral complex and from the central densocellular, paracentral, and mediodorsal nuclei. These projection patterns are in line with the functional properties of injected areas: "dorsal stream" extrastriate area V6 receives information from visuotopically organised subdivisions of the thalamus; whereas visuomotor area V6A, which is involved in the sensory guidance of arm movement, receives its primary afferents from thalamic nuclei that provide high-order somatic and visual input.

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. II. Stereologic analysis of chemoarchitecture.

PubMed

Sherwood, Chet C; Holloway, Ralph L; Erwin, Joseph M; Hof, Patrick R

2004-01-01

This study presents a comparative stereologic investigation of neurofilament protein- and calcium-binding protein-immunoreactive neurons within the region of orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens). Results showed that the density of interneurons involved in vertical interlaminar processing (i.e., calbindin- and calretinin-immunoreactive neurons) as well pyramidal neurons that supply heavily-myelinated projections (i.e., neurofilament protein-immunoreactive neurons) are correlated with overall neuronal density, whereas interneurons making transcolumnar connections (i.e., parvalbumin-immunoreactive neurons) do not exhibit such a relationship. These results suggest that differential scaling rules apply to different neuronal subtypes depending on their functional role in cortical circuitry. For example, cortical columns across catarrhine species appear to involve a similar conserved network of intracolumnar inhibitory interconnections, as represented by the distribution of calbindin- and calretinin-immunoreactive neurons. The subpopulation of horizontally-oriented wide-arbor interneurons, on the other hand, increases in density relative to other interneuron subpopulations in large brains. Due to these scaling trends, the region of orofacial representation of primary motor cortex in great apes and humans is characterized by a greater proportion of neurons enriched in neurofilament protein and parvalbumin compared to the Old World monkeys examined. These modifications might contribute to the voluntary dexterous control of orofacial muscles in great ape and human communication. Copyright 2004 S. Karger AG, Basel

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. I. Quantitative analysis of cytoarchitecture.

PubMed

Sherwood, Chet C; Holloway, Ralph L; Erwin, Joseph M; Schleicher, Axel; Zilles, Karl; Hof, Patrick R

2004-01-01

Social life in anthropoid primates is mediated by interindividual communication, involving movements of the orofacial muscles for the production of vocalization and gestural expression. Although phylogenetic diversity has been reported in the auditory and visual communication systems of primates, little is known about the comparative neuroanatomy that subserves orofacial movement. The current study reports results from quantitative image analysis of the region corresponding to orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens) using the Grey Level Index method. This cortical region has been implicated in the execution of skilled motor activities such as voluntary facial expression and human speech. Density profiles of the laminar distribution of Nissl-stained neuronal somata were acquired from high-resolution images to quantify cytoarchitectural patterns. Despite general similarity in these profiles across catarrhines, multivariate analysis showed that cytoarchitectural patterns of individuals were more similar within-species versus between-species. Compared to Old World monkeys, the orofacial representation of area 4 in great apes and humans was characterized by an increased relative thickness of layer III and overall lower cell volume densities, providing more neuropil space for interconnections. These phylogenetic differences in microstructure might provide an anatomical substrate for the evolution of greater volitional fine motor control of facial expressions in great apes and humans. Copyright 2004 S. Karger AG, Basel

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

PubMed

Mubiru, James N; Yang, Alice S; Olsen, Christian; Nayak, Sudhir; Livi, Carolina B; Dick, Edward J; Owston, Michael; Garcia-Forey, Magdalena; Shade, Robert E; Rogers, Jeffrey

2014-01-01

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

First description of the surgical anatomy of the cynomolgus monkey liver.

PubMed

Vons, Corinne; Beaudoin, Sylvie; Helmy, Nada; Dagher, Ibrahim; Weber, Anne; Franco, Dominique

2009-05-01

No detailed description of nonhuman primate liver anatomy has been reported and little is known about the similarity between such livers and human liver. The cynomolgus monkey (Macaca fascicularis) was used to establish a preclinical model of genetically modified hepatocytes auto transplantation. Here, we report information gleaned from careful observation and notes obtained from 59 female cynomolgus monkeys undergoing 44 anatomical hepatic resections, 12 main portal vein division dissections and selective branch ligations, and 46 portographies. Additionally, three anatomical liver dissections after total resection at autopsy were performed and served to confirm peroperative observations and for photography to provide illustrations. Our results indicate that the cynomolgus monkey liver has four lobes: the median (the largest), the right and left lateral, and the caudate lobes. In 60% (N=20) of individuals the portal bifurcates into right and left portal veins, in the remaining 40% (N=14) the portal vein trifurcates into right anterior, right posterior, and left portal veins. The anatomy and branching pattern of the hepatic artery and bile ducts closely follow those of the portal branches. Functionally, the cynomolgus monkey liver can be divided into eight independent segments. Thus, we report the first detailed description of the hepatic and portal surgical anatomy of the cynomolgus monkey. The cynomolgus monkey liver is more similar to the human liver than are livers of any small or large nonprimate mammals that have been described. (c) 2009 Wiley-Liss, Inc.

Temperament in rhesus, long-tailed, and pigtailed macaques varies by species and sex

PubMed Central

Sussman, Adrienne F.; Ha, James C.; Bentson, Kathy L.; Crockett, Carolyn M.

2012-01-01

Temperament differs among individuals both within and between species. Evidence suggests that differences in temperament of group members may parallel differences in social behavior among groups or between species. Here, we compared temperament between three closely related species of monkey - rhesus (Macaca mulatta), long-tailed (M. fascicularis), and pigtailed (M. nemestrina) macaques - using cage-front behavioral observations of individually housed monkeys at a National Primate Research Center. Frequencies of 12 behaviors in 899 subjects were analyzed using a PCA to identify temperament components. The analysis identified four components, which we interpreted as Sociability towards humans, Cautiousness, Aggressiveness, and Fearfulness. Species and sexes differed in their average scores on these components, even after controlling for differences in age and early-life experiences. Our results suggest that rhesus macaques are especially aggressive and unsociable towards humans, long-tailed macaques are more cautious and fearful, and pigtailed macaques are more sociable towards humans and less aggressive than the other species. Pigtailed males were notably more sociable than any other group. The differences observed are consistent with reported variation in these species’ social behaviors, as rhesus macaques generally engage in more social aggression and pigtailed macaques engage in more male-male affiliative behaviors. Differences in predation risks are among the socioecological factors that might make these species-typical behaviors adaptive. Our results suggest that adaptive species-level social differences may be encoded in individual-level temperaments, which are manifested even outside of a social context. PMID:23225368

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

PubMed Central

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

Developing a musculoskeletal model of the primate skull: predicting muscle activations, bite force, and joint reaction forces using multibody dynamics analysis and advanced optimisation methods.

PubMed

Shi, Junfen; Curtis, Neil; Fitton, Laura C; O'Higgins, Paul; Fagan, Michael J

2012-10-07

An accurate, dynamic, functional model of the skull that can be used to predict muscle forces, bite forces, and joint reaction forces would have many uses across a broad range of disciplines. One major issue however with musculoskeletal analyses is that of muscle activation pattern indeterminacy. A very large number of possible muscle force combinations will satisfy a particular functional task. This makes predicting physiological muscle recruitment patterns difficult. Here we describe in detail the process of development of a complex multibody computer model of a primate skull (Macaca fascicularis), that aims to predict muscle recruitment patterns during biting. Using optimisation criteria based on minimisation of muscle stress we predict working to balancing side muscle force ratios, peak bite forces, and joint reaction forces during unilateral biting. Validation of such models is problematic; however we have shown comparable working to balancing muscle activity and TMJ reaction ratios during biting to those observed in vivo and that peak predicted bite forces compare well to published experimental data. To our knowledge the complexity of the musculoskeletal model is greater than any previously reported for a primate. This complexity, when compared to more simple representations provides more nuanced insights into the functioning of masticatory muscles. Thus, we have shown muscle activity to vary throughout individual muscle groups, which enables them to function optimally during specific masticatory tasks. This model will be utilised in future studies into the functioning of the masticatory apparatus. Copyright © 2012 Elsevier Ltd. All rights reserved.

Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques

PubMed Central

Campbell, Kevin J.; Detmer, Ann M.; Karl, Julie A.; Wiseman, Roger W.; Blasky, Alex J.; Hughes, Austin L.; Bimber, Benjamin N.; O’Connor, Shelby L.; O’Connor, David H.

2009-01-01

Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for infectious disease research. Several geographically distinct populations of these macaques from Southeast Asia and the Indian Ocean island of Mauritius are available for pathogenesis studies. Though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. In this study we identified 47 full-length MHC class I nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority of MHC class I sequences characterized (39 of 47) were unique to this regional population. However, we discovered eight sequences with perfect identity and six sequences with close similarity to previously defined MHC class I sequences from other macaque populations. We identified two ancestral MHC haplotypes that appear to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B haplotype that has previously been shown to protect Mauritian cynomolgus macaques against challenge with a simian/human immunodeficiency virus, SHIV89.6P. We also identified a Filipino cynomolgus macaque MHC class I sequence for which the predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is important because Mamu-B*17 is strongly associated with protection against simian immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols. PMID:19107381

Behavioral and neurobiological characteristics influencing social hierarchy formation in female cynomolgus monkeys.

PubMed

Riddick, N V; Czoty, P W; Gage, H D; Kaplan, J R; Nader, S H; Icenhower, M; Pierre, P J; Bennett, A; Garg, P K; Garg, S; Nader, M A

2009-02-18

Socially housed monkeys have been used as a model to study human diseases. The present study examined behavioral, physiological and neurochemical measures as predictors of social rank in 16 experimentally naïve, individually housed female cynomolgus monkeys (Macaca fascicularis). The two behavioral measures examined were novel object reactivity (NOR), as determined by latency to touch an opaque acrylic box placed in the home cage, and locomotor activity assessed in a novel open-field apparatus. Serum cortisol concentrations were evaluated three times per week for four consecutive weeks, and stress reactivity was assessed on one occasion by evaluating the cortisol response to adrenocorticotropic hormone (ACTH) following dexamethasone suppression. Measures of serotonin (5-HT) function included whole blood 5-HT (WBS) concentrations, cerebrospinal fluid (CSF) concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) and brain 5-HT transporter (SERT) availability obtained using positron emission tomography (PET). After baseline measures were obtained, monkeys were assigned to four social groups of four monkeys per group. The two measures that correlated with eventual social rank were CSF 5-HIAA concentrations, which were significantly higher in the animals who eventually became subordinate, and latency to touch the novel object, which was significantly lower in eventual subordinate monkeys. Measures of 5-HT function did not change as a consequence of social rank. These data suggest that levels of central 5-HIAA and measures of novel object reactivity may be trait markers that influence eventual social rank in female macaques.

Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach

PubMed Central

Shaylor, Lara A.; Hwang, Sung Jin; Sanders, Kenton M.

2016-01-01

Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1−/−) and P2Y1 receptors (P2ry1−/−) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1−/− mice IJPs and relaxations persisted whereas in P2ry1−/− mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species. PMID:27634009

Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach.

PubMed

Shaylor, Lara A; Hwang, Sung Jin; Sanders, Kenton M; Ward, Sean M

2016-11-01

Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1 -/- ) and P2Y1 receptors (P2ry1 -/- ) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1 -/- mice IJPs and relaxations persisted whereas in P2ry1 -/- mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species. Copyright © 2016 the American Physiological Society.

Utah optrode array customization using stereotactic brain atlases and 3-D CAD modeling for optogenetic neocortical interrogation in small rodents and nonhuman primates.

PubMed

Boutte, Ronald W; Merlin, Sam; Yona, Guy; Griffiths, Brandon; Angelucci, Alessandra; Kahn, Itamar; Shoham, Shy; Blair, Steve

2017-10-01

As the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks ® computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey ( Macaca fascicularis ) visual cortex. The 3-D CAD model of the brain was used to customize an [Formula: see text] Utah optrode array (UOA) after it was determined that a high-density ([Formula: see text]) UOA caused extensive damage to marmoset ( Callithrix jacchus ) primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.5-mm-diameter through glass via. The [Formula: see text] UOA was customized for optrode length ([Formula: see text]), optrode width ([Formula: see text]), optrode pitch ([Formula: see text]), backplane thickness ([Formula: see text]), and overall form factor ([Formula: see text]). Two [Formula: see text] UOAs were inserted into layer VI of macaque V4D cortices with minimal damage as assessed in fixed tissue cytochrome oxidase staining in nonrecoverable surgeries. Additionally, two [Formula: see text] arrays were implanted in mice ( Mus musculus ) motor cortices, providing early evidence for long-term tolerability (over 6 months), and for the ability to integrate the UOA with a Holobundle light delivery system toward patterned optogenetic stimulation of cortical networks.

A Central Mesencephalic Reticular Formation Projection to the Supraoculomotor Area in Macaque Monkeys

PubMed Central

Bohlen, Martin O.; Warren, Susan; May, Paul J.

2015-01-01

The central mesencephalic reticular formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system’s premotor circuitry. This study in Macaca fascicularis monkeys investigates the pattern of central mesencephalic reticular formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. It also examines the location of the cells responsible for this projection. Injections of biotinylated dextran amine were stereotaxically placed within the central mesencephalic reticular formation to anterogradely label axons and terminals. These revealed bilateral terminal fields in the supraoculomotor area. In addition, dense terminations were found in both the preganglionic Edinger-Westphal nuclei. The dense terminations just dorsal to the oculomotor nucleus overlap with the location of the C-group medial rectus motoneurons projecting to multiply innervated muscle fibers suggesting they may be targeted. Minor terminal fields were observed bilaterally within the borders of the oculomotor and abducens nuclei. Injections including the supraoculomotor area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing the central third of the central mesencephalic reticular formation at all rostrocaudal levels, indicating a subregion of the nucleus provides this projection. Thus, these experiments reveal that a subregion of the central mesencephalic reticular formation may directly project to motoneurons in the oculomotor and abducens nuclei, as well as to preganglionic neurons controlling the tone of intraocular muscles. This pattern of projections suggests an as yet undetermined role in regulating the near triad. PMID:25859632

A central mesencephalic reticular formation projection to the supraoculomotor area in macaque monkeys.

PubMed

Bohlen, Martin O; Warren, Susan; May, Paul J

2016-05-01

The central mesencephalic reticular formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system's premotor circuitry. This study in Macaca fascicularis monkeys investigates the pattern of central mesencephalic reticular formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. It also examines the location of the cells responsible for this projection. Injections of biotinylated dextran amine were stereotaxically placed within the central mesencephalic reticular formation to anterogradely label axons and terminals. These revealed bilateral terminal fields in the supraoculomotor area. In addition, dense terminations were found in both the preganglionic Edinger-Westphal nuclei. The dense terminations just dorsal to the oculomotor nucleus overlap with the location of the C-group medial rectus motoneurons projecting to multiply innervated muscle fibers suggesting they may be targeted. Minor terminal fields were observed bilaterally within the borders of the oculomotor and abducens nuclei. Injections including the supraoculomotor area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing the central third of the central mesencephalic reticular formation at all rostrocaudal levels, indicating a subregion of the nucleus provides this projection. Thus, these experiments reveal that a subregion of the central mesencephalic reticular formation may directly project to motoneurons in the oculomotor and abducens nuclei, as well as to preganglionic neurons controlling the tone of intraocular muscles. This pattern of projections suggests an as yet undetermined role in regulating the near triad.

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

PubMed

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.

Antiviral efficacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques.

PubMed

Guedj, Jérémie; Piorkowski, Géraldine; Jacquot, Frédéric; Madelain, Vincent; Nguyen, Thi Huyen Tram; Rodallec, Anne; Gunther, Stephan; Carbonnelle, Caroline; Mentré, France; Raoul, Hervé; de Lamballerie, Xavier

2018-03-01

Despite repeated outbreaks, in particular the devastating 2014-2016 epidemic, there is no effective treatment validated for patients with Ebola virus disease (EVD). Among the drug candidates is the broad-spectrum polymerase inhibitor favipiravir, which showed a good tolerance profile in patients with EVD (JIKI trial) but did not demonstrate a strong antiviral efficacy. In order to gain new insights into the antiviral efficacy of favipiravir and improve preparedness and public health management of future outbreaks, we assess the efficacy achieved by ascending doses of favipiravir in Ebola-virus-infected nonhuman primates (NHPs). A total of 26 animals (Macaca fascicularis) were challenged intramuscularly at day 0 with 1,000 focus-forming units of Ebola virus Gabon 2001 strain and followed for 21 days (study termination). This included 13 animals left untreated and 13 treated with doses of 100, 150, and 180 mg/kg (N = 3, 5, and 5, respectively) favipiravir administered intravenously twice a day for 14 days, starting 2 days before infection. All animals left untreated or treated with 100 mg/kg died within 10 days post-infection, while animals receiving 150 and 180 mg/kg had extended survival (P < 0.001 and 0.001, respectively, compared to untreated animals), leading to a survival rate of 40% (2/5) and 60% (3/5), respectively, at day 21. Favipiravir inhibited viral replication (molecular and infectious viral loads) in a drug-concentration-dependent manner (P values < 0.001), and genomic deep sequencing analyses showed an increase in virus mutagenesis over time. These results allowed us to identify that plasma trough favipiravir concentrations greater than 70-80 μg/ml were associated with reduced viral loads, lower virus infectivity, and extended survival. These levels are higher than those found in the JIKI trial, where patients had median trough drug concentrations equal to 46 and 26 μg/ml at day 2 and day 4 post-treatment, respectively, and suggest that the dosing

Retinal response of Macaca mulatta to picosecond laser pulses of varying energy and spot size.

PubMed

Roach, William P; Cain, Clarence P; Narayan, Drew G; Noojin, Gary D; Boppart, Stephen A; Birngruber, Reginald; Fujimoto, James G; Toth, Cynthia A

2004-01-01

We investigate the relationship between the laser beam at the retina (spot size) and the extent of retinal injury from single ultrashort laser pulses. From previous studies it is believed that the retinal effect of single 3-ps laser pulses should vary in extent and location, depending on the occurrence of laser-induced breakdown (LIB) at the site of laser delivery. Single 3-ps pulses of 580-nm laser energy are delivered over a range of spot sizes to the retina of Macaca mulatta. The retinal response is captured sequentially with optical coherence tomography (OCT). The in vivo OCT images and the extent of pathology on final microscopic sections of the laser site are compared. With delivery of a laser pulse with peak irradiance greater than that required for LIB, OCT and light micrographs demonstrate inner retinal injury with many intraretinal and/or vitreous hemorrhages. In contrast, broad outer retinal injury with minimal to no choriocapillaris effect is seen after delivery of laser pulses to a larger retinal area (60 to 300 microm diam) when peak irradiance is less than that required for LIB. The broader lesions extend into the inner retina when higher energy delivery produces intraretinal injury. Microscopic examination of stained fixed tissues provide better resolution of retinal morphology than OCT. OCT provides less resolution but could be guided over an in vivo, visible retinal lesion for repeated sampling over time during the evolution of the lesion formation. For 3-ps visible wavelength laser pulses, varying the spot size and laser energy directly affects the extent of retinal injury. This again is believed to be partly due to the onset of LIB, as seen in previous studies. Spot-size dependence should be considered when comparing studies of retinal effects or when pursuing a specific retinal effect from ultrashort laser pulses. Copyright 2004 Society of Photo-Optical Instrumentation Engineers.

The influence of kinship and dominance hierarchy on grooming partner choice in free-ranging Macaca mulatta brevicaudus.

PubMed

Wu, Cheng-Feng; Liao, Zhi-Jie; Sueur, Cedric; Sha, John Chih Mun; Zhang, Jie; Zhang, Peng

2018-04-18

In group-living animals, individuals do not interact uniformly with their conspecifics. Among primates, such heterogeneity in partner choice can be discerned from affiliative grooming patterns. While the preference for selecting close kin as grooming partners is ubiquitous across the primate order, the selection of higher-ranking non-kin individuals as grooming partners is less common. We studied a group of provisioned rhesus macaques (Macaca mulatta brevicaudus) on Hainan Island, China, to examine rank-related benefits of grooming exchanges and the influence of kin relationships. We tested four hypotheses based on Seyfarth's model: (1) there will be kin preference in grooming relationships; (2) grooming between non-kin individuals will be directed up the dominance rank; (3) grooming between non-kin individuals will reduce aggression from higher-ranking ones; and (4) non-kin individuals will spend more time grooming with adjacent ranked ones. We found that grooming relationships between kin individuals were stronger than those between non-kin individuals. For non-kin relationships, lower-ranking individuals received less aggression from higher-ranking ones through grooming; a benefit they could not derive through grooming exchanges with individuals related by kinship. Individuals spent more time grooming adjacent higher-ranking non-kin individuals and higher-ranking individuals also received more grooming from non-kin individuals. Our results supported Seyfarth's model for predicting partner choice between non-kin individuals. For relationships between kin individuals, we found results that were not consistent with prediction for the exchanges of aggression and grooming, indicating the importance to control for the influence of kinship in future studies.

Influence of dominance rank and affiliation relationships on self-directed behavior in female Tibetan macaques (Macaca thibetana).

PubMed

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.

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta).

PubMed

Freeman, Sara M; Inoue, Kiyoshi; Smith, Aaron L; Goodman, Mark M; Young, Larry J

2014-07-01

The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication. Copyright © 2014 Elsevier Ltd. All rights reserved.

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

PubMed Central

Freeman, Sara M.; Inoue, Kiyoshi; Smith, Aaron L.; Goodman, Mark M.; Young, Larry J.

2014-01-01

The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication. PMID:24845184

Delayed effects of proton irradiation in Macaca Mulatta (22-year summary)

NASA Astrophysics Data System (ADS)

Woods, D. H.; Hardy, K. A.; Cox, A. B.; Salmon, Y. L.; Yochmowitz, M. G.; Cordts, R. E.

1989-05-01

Lifetime observations on a group of rhesus monkeys indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be correlated with the dose and energy of radiation. The primary cause of life shortening is nonleukemic cancers. Radiation also increased the rise of endometriosis (an abnormal proliferation of the lining of the uterus in females). Other effects associated with radiation exposures are lowered glucose tolerance and increased incidence of cataracts. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total body surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of humans is, therefore, critical to the assessment of lifetime cancer risk.

Delayed effects of proton irradiation in Macaca Mulatta (22-year summary)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woods, D.H.; Hardy, K.A.; Cox, A.B.

1989-05-15

Lifetime observations on a group of rhesus monkeys indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be correlated with the dose and energy of radiation. The primary cause of life shortening is nonleukemic cancers. Radiation also increased the rise of endometriosis (an abnormal proliferation of the lining of the uterus in females). Other effects associated with radiation exposures are lowered glucose tolerance and increased incidence of cataracts. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total bodymore » surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of humans is, therefore, critical to the assessment of lifetime cancer risk.« less

Dose specification for radiation therapy: dose to water or dose to medium?

NASA Astrophysics Data System (ADS)

Ma, C.-M.; Li, Jinsheng

2011-05-01

The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

Division of Labor in Hand Usage Is Associated with Higher Hand Performance in Free-Ranging Bonnet Macaques, Macaca radiata

PubMed Central

Mangalam, Madhur; Desai, Nisarg; Singh, Mewa

2015-01-01

A practical approach to understanding lateral asymmetries in body, brain, and cognition would be to examine the performance advantages/disadvantages associated with the corresponding functions and behavior. In the present study, we examined whether the division of labor in hand usage, marked by the preferential usage of the two hands across manual operations requiring maneuvering in three-dimensional space (e.g., reaching for food, grooming, and hitting an opponent) and those requiring physical strength (e.g., climbing), is associated with higher hand performance in free-ranging bonnet macaques, Macaca radiata. We determined the extent to which the macaques exhibit laterality in hand usage in an experimental unimanual and a bimanual food-reaching task, and the extent to which manual laterality is associated with hand performance in an experimental hand-performance-differentiation task. We observed negative relationships between (a) the latency in food extraction by the preferred hand in the hand-performance-differentiation task (wherein, lower latency implies higher performance), the preferred hand determined using the bimanual food-reaching task, and the normalized difference between the performance of the two hands, and (b) the normalized difference between the performance of the two hands and the absolute difference between the laterality in hand usage in the unimanual and the bimanual food-reaching tasks (wherein, lesser difference implies higher manual specialization). Collectively, these observations demonstrate that the division of labor between the two hands is associated with higher hand performance. PMID:25806511

Arboreal adaptations of body fat in wild toque macaques (Macaca sinica) and the evolution of adiposity in primates.

PubMed

Dittus, Wolfgang P J

2013-11-01

There is a paucity of information on body composition and fat patterning in wild nonhuman primates. Dissected adipose tissue from wild toque macaques (Macaca sinica) (WTM), feeding on a natural diet, accounted for 2.1% of body weight. This was far less than fatness reported for nonhuman primates raised in captivity or for contemporary humans. In WTM, fatness increased with age and diet richness, but did not differ by sex. In WTM (none of which were obese) intra-abdominal fat filled first, and "excess" fat was stored peripherally in a ratio of about 6:1. Intermuscular fat was minimal (0.1%). The superficial paunch held <15% of subcutaneous fat weight in contrast to its much larger proportions in obese humans and captive monkeys where most added fat accumulates subcutaneously. With increasing total adiposity, accumulating fat shifted in its distribution among eight different main internal and peripheral deposit areas-consistent with maintaining body balance and a low center of gravity. The available data suggest that, in arboreal primates, adaptations for agile locomotion and terminal branch feeding set constraints on the quantity and distribution of fat. The absence of a higher percentage of body fat in females and neonates (as are typical of humans) suggests that arboreal adaptations preclude the development of fat-dependent, large-brained infants and the adipose-rich mothers needed to sustain them. The lifestyle and body composition of wild primates represent a more appropriate model for early human foragers than well-fed captive monkeys do. Copyright © 2013 Wiley Periodicals, Inc.

Effect of sodium meclofenamate on radiation-induced esophagitis and cystitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ambrus, J.L.; Ambrus, C.M.; Lillie, D.B.

Stumptailed monkeys (Macaca arctoides) received 2000 rad irradiation to the upper half of the esophagus and to the bladder by a 6-MeV linear accelerator. Endoscopy and biopsy was obtained from these organs weekly for 3 weeks. At the end of this period, the animals were autopsied and histopathologic examination undertaken. Sodium meclofenamate in doses of 5-20 mg/kg/day p.os was found effective in reducing or preventing radiation-induced esophagitis and cystitis.

Palisade endings: cholinergic sensory organs or effector organs?

PubMed

Blumer, Roland; Konakci, Kadriye Zeynep; Pomikal, Christine; Wieczorek, Grazyna; Lukas, Julius-Robert; Streicher, Johannes

2009-03-01

This study aims to complement the authors' prior findings on palisade endings in extraocular muscles (EOMs) of monkeys, and to clarify whether palisade endings are cholinergic motor or cholinergic sensory. Macaque monkeys (Macaca fascicularis, n = 10) of both sexes were analyzed using three-dimensional (3D) reconstructions, confocal laser scanning microscopy (CLSM), and conventional/immuno transmission electron microscopy (TEM). For CLSM, we used three combinations of triple fluorescent labeling. EOM wholemounts were labeled with cholinergic markers, including choline acetyltransferase (ChAT), choline transporter (ChT), vesicular acetylcholine transporter (VAChT), and a classical postsynaptic marker for motor terminals, namely alpha-bungarotoxin. Muscle fibers were counterstained with phalloidin. 3D reconstructions were done of triple-labeled palisade endings. For immuno TEM, tissue was labeled with antibody against ChAT. Concordant with prior findings, the authors demonstrated that palisade endings at the muscle fiber tips arose from nerve fibers that are ChAT-positive. In 25% of the cases, axons forming palisade endings established multiple neuromuscular contacts outside the palisade complex. Such additional neuromuscular contacts were motor terminals, as demonstrated by alpha-bungarotoxin binding. All palisade endings established nerve terminals on the tendon. In 40% of the palisade endings, nerve terminals were observed on the muscle fiber as well. Neurotendinous contacts and neuromuscular contacts in palisade endings were ChT/ChAT/VAChT-immunoreactive. Neuromuscular contacts exhibited structural features of motor terminals and were also alpha-bungarotoxin positive. The present study ascertained that palisade endings are cholinergic motor organs. Therefore, it was concluded that palisade endings are not candidates to provide eye-position signals.

The Effect of Short Moderate Stress on the Midbrain CRF System in a Macaque Model of Functional Hypothalamic Amenorrhea

PubMed Central

Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

2014-01-01

Objective To study the effect of moderate stress on CRF components in the serotonergic midbrain region in a monkey model of FHA. Design After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days prior to euthanasia. Setting University of Pittsburgh nonhuman primate facility. Animals Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n=5), medium stress resilient (MSR, N=4) or stress sensitive (SS, n=4). Intervention 5 days of diet in a novel room with unfamiliar conspecifics. Main Outcome Measures Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of UCN1 cells; the density of UCN1 axons; the expression of CRF-R1 and CRF-R2 in the dorsal raphe nucleus. Results CRF innervation was higher in HSR than SS animals; UCN1 cell number was higher in HSR than SS animals and UCN1 axon bouton density was not different, all opposite of non-stressed animals. CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than SS animals. The relative expression of CRF-R1 and R2 was similar to non-stressed animals. Conclusions HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. PMID:23849846

Induction of pluripotent stem cells from a cynomolgus monkey using a polycistronic simian immunodeficiency virus-based vector, differentiation toward functional cardiomyocytes, and generation of stably expressing reporter lines.

PubMed

Wunderlich, Stephanie; Haase, Alexandra; Merkert, Sylvia; Beier, Jennifer; Schwanke, Kristin; Schambach, Axel; Glage, Silke; Göhring, Gudrun; Curnow, Eliza C; Martin, Ulrich

2012-12-01

Induced pluripotent stem cells (iPSCs) represent a novel cell source for regenerative therapies. Many emerging iPSC-based therapeutic concepts will require preclinical evaluation in suitable large animal models. Among the large animal species frequently used in preclinical efficacy and safety studies, macaques show the highest similarities to humans at physiological, cellular, and molecular levels. We have generated iPSCs from cynomolgus monkeys (Macaca fascicularis) as a segue to regenerative therapy model development in this species. Because typical human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors show poor transduction of simian cells, a simian immunodeficiency virus (SIV)-based vector was chosen for efficient transduction of cynomolgus skin fibroblasts. A corresponding polycistronic vector with codon-optimized reprogramming factors was constructed for reprogramming. Growth characteristics as well as cell and colony morphology of the resulting cynomolgus iPSCs (cyiPSCs) were demonstrated to be almost identical to cynomolgus embryonic stem cells (cyESCs), and cyiPSCs expressed typical pluripotency markers including OCT4, SOX2, and NANOG. Furthermore, differentiation in vivo and in vitro into derivatives of all three germ layers, as well as generation of functional cardiomyocytes, could be demonstrated. Finally, a highly efficient technique for generation of transgenic cyiPSC clones with stable reporter expression in undifferentiated cells as well as differentiated transgenic cyiPSC progeny was developed to enable cell tracking in recipient animals. In conclusion, our data indicate that cyiPSCs represent a valuable cell source for establishment of macaque-based allogeneic and autologous preclinical cell transplantation models for various fields of regenerative medicine.

Anatomical Evidence that the Superior Colliculus Controls Saccades through Central Mesencephalic Reticular Formation Gating of Omnipause Neuron Activity

PubMed Central

Wang, Niping; Perkins, Eddie; Zhou, Lan; Warren, Susan

2013-01-01

Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectum's saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC–cMRF–RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF. PMID:24107960

Color vision test for dichromatic and trichromatic macaque monkeys.

PubMed

Koida, Kowa; Yokoi, Isao; Okazawa, Gouki; Mikami, Akichika; Widayati, Kanthi Arum; Miyachi, Shigehiro; Komatsu, Hidehiko

2013-11-01

Dichromacy is a color vision defect in which one of the three cone photoreceptors is absent. Individuals with dichromacy are called dichromats (or sometimes "color-blind"), and their color discrimination performance has contributed significantly to our understanding of color vision. Macaque monkeys, which normally have trichromatic color vision that is nearly identical to humans, have been used extensively in neurophysiological studies of color vision. In the present study we employed two tests, a pseudoisochromatic color discrimination test and a monochromatic light detection test, to compare the color vision of genetically identified dichromatic macaques (Macaca fascicularis) with that of normal trichromatic macaques. In the color discrimination test, dichromats could not discriminate colors along the protanopic confusion line, though trichromats could. In the light detection test, the relative thresholds for longer wavelength light were higher in the dichromats than the trichromats, indicating dichromats to be less sensitive to longer wavelength light. Because the dichromatic macaque is very rare, the present study provides valuable new information on the color vision behavior of dichromatic macaques, which may be a useful animal model of human dichromacy. The behavioral tests used in the present study have been previously used to characterize the color behaviors of trichromatic as well as dichromatic new world monkeys. The present results show that comparative studies of color vision employing similar tests may be feasible to examine the difference in color behaviors between trichromatic and dichromatic individuals, although the genetic mechanisms of trichromacy/dichromacy is quite different between new world monkeys and macaques.

Nonhuman anthropoid primate femoral neck trabecular architecture and its relationship to locomotor mode.

PubMed

Fajardo, Roberto J; Müller, Ralph; Ketcham, Rich A; Colbert, Matthew

2007-04-01

Functional analyses of human and nonhuman anthropoid primate femoral neck structure have largely ignored the trabecular bone. We tested hypotheses regarding differences in the relative distribution and structural anisotropy of trabecular bone in the femoral neck of quadrupedal and climbing/suspensory anthropoids. We used high-resolution X-ray computed tomography to analyze quantitatively the femoral neck trabecular structure of Ateles geoffroyi, Symphalangus syndactylus, Alouatta seniculus, Colobus guereza, Macaca fascicularis, and Papio cynocephalus (n = 46). We analyzed a size-scaled superior and inferior volume of interest (VOI) in the femoral neck. The ratio of the superior to inferior VOI bone volume fraction indicated that the distribution of trabecular bone was inferiorly skewed in most (but not all) quadrupeds and evenly distributed the climbing/suspensory species, but interspecific comparisons indicated that all taxa overlapped in these measurements. Degree of anisotropy values were generally higher in the inferior VOI of all species and the results for the two climbing/suspensory taxa, A. geoffroyi (1.71 +/- 0.30) and S. syndactylus (1.55 +/- 0.04), were similar to the results for the quadrupedal anthropoids, C. guereza (male = 1.64 +/- 0.13; female = 1.68 +/- 0.07) and P. cynocephalus (1.47 +/- 0.13). These results suggest strong trabecular architecture similarity across body sizes, anthropoid phylogenetic backgrounds, and locomotor mode. This structural similarity might be explained by greater similarity in anthropoid hip joint loading mechanics than previously considered. It is likely that our current models of anthropoid hip joint mechanics are overly simplistic.

The effect of short moderate stress on the midbrain corticotropin-releasing factor system in a macaque model of functional hypothalamic amenorrhea.

PubMed

Bethea, Cynthia L; Phu, Kenny; Reddy, Arubala P; Cameron, Judy L

2013-10-01

To study the effect of moderate stress on corticotropin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea. After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia. Primate research center. Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4). Five days of diet in a novel room with unfamiliar conspecifics. Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus. The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals. The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A suitable method for the detection of a potential fraud of bringing macaque monkey meat into the food chain.

PubMed

Rashid, Nur Raifana Abdul; Ali, Md Eaqub; Hamid, Sharifah Bee Abd; Rahman, Md Mahfujur; Razzak, Md Abdur; Asing; Amin, Md Al

2015-01-01

Being the third-largest primate population has not made macaque (Macaca fascicularis sp.) monkeys less exposed to threats and dangers. Despite wildlife protection, they have been widely hunted and consumed in several countries because of their purported nutritional values. In addition to trading as pure bush meats in several places, monkey meat has been sold in meatball and soup products in Indonesia. Thus the possibility of macaque meat trafficking under the label of common meats is quite high. This paper reports the development of a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with the shortest amplicon length for the confirmed detection of monkey meat under compromised states which are known to degrade DNA. We amplified a 120-bp region of d-loop gene using a pair of macaque-specific primers and confirmed their specificity for the target species through cross-challenging against 17 different species using a 141-bp site of an 18 S rRNA gene as an endogenous control for eukaryotes. This eliminated the possibilities of any false-negative detection with complex matrices or degraded specimens. The detection limit was 0.00001 ng DNA in a pure state and 0.1% of meat in mixed matrices and commercial meatball products. RFLP analysis further authenticated the originality of the PCR product and distinctive restriction patterns were found upon AluI and CViKI-1 digestion. A micro-fluidic lab-on-a-chip automated electrophoretic system separated the fragments with high resolution. The assay was validated for screening commercial meatball products with sufficient internal control.

Balancing the spatial demands of the developing dentition with the mechanical demands of the catarrhine mandibular symphysis

PubMed Central

Cobb, Samuel N; Panagiotopoulou, Olga

2011-01-01

The superior transverse torus of the catarrhine mandible has been shown to effectively reduce bending at the symphysis during unilateral postcanine biting. While the adult superior transverse torus contains trabecular bone, the juvenile one is almost entirely filled by developing permanent incisors until their eruption. This study uses finite elements analysis (FEA) to investigate whether the presence of developing incisors in the juvenile symphysis increases strains on the superior transverse torus. Two FE models of a juvenile Macaca fascicularis mandible were created: one included all the developing teeth; the second was modified to remove the incisor tooth crypts by filling them with trabecular bone. The models were loaded identically to simulate static physiological unilateral biting on dp4 and strain magnitudes, patterns and distributions of the two FE models were compared. The FEA results show a notable increase in strain magnitudes by up to 40% when the developing incisors are present. The results indicate that, in order to maintain the same symphyseal strain magnitudes during chewing, the presence of the incisors in the symphysis necessitates a larger superior transverse torus in the juvenile than would be required if the superior transverse torus did not house the developing incisors. These results highlight the adaptational balance of the symphyseal morphology throughout ontogeny between biomechanics and the spatial demands of the developing dentition. Based on the findings we therefore propose that the spatial requirements of the developing incisors during ontogeny can act as a constraint on the functional adaptation and subsequent adult morphology observed in the catarrhine mandibular symphysis. PMID:21158857

Intergroup variation in robbing and bartering by long-tailed macaques at Uluwatu Temple (Bali, Indonesia).

PubMed

Brotcorne, Fany; Giraud, Gwennan; Gunst, Noëlle; Fuentes, Agustín; Wandia, I Nengah; Beudels-Jamar, Roseline C; Poncin, Pascal; Huynen, Marie-Claude; Leca, Jean-Baptiste

2017-10-01

Robbing and bartering (RB) is a behavioral practice anecdotally reported in free-ranging commensal macaques. It usually occurs in two steps: after taking inedible objects (e.g., glasses) from humans, the macaques appear to use them as tokens, returning them to humans in exchange for food. While extensively studied in captivity, our research is the first to investigate the object/food exchange between humans and primates in a natural setting. During a 4-month study in 2010, we used both focal and event sampling to record 201 RB events in a population of long-tailed macaques (Macaca fascicularis), including four neighboring groups ranging freely around Uluwatu Temple, Bali (Indonesia). In each group, we documented the RB frequency, prevalence and outcome, and tested the underpinning anthropogenic and demographic determinants. In line with the environmental opportunity hypothesis, we found a positive qualitative relation at the group level between time spent in tourist zones and RB frequency or prevalence. For two of the four groups, RB events were significantly more frequent when humans were more present in the environment. We also found qualitative partial support for the male-biased sex ratio hypothesis [i.e., RB was more frequent and prevalent in groups with higher ratios of (sub)adult males], whereas the group density hypothesis was not supported. This preliminary study showed that RB is a spontaneous, customary (in some groups), and enduring population-specific practice characterized by intergroup variation in Balinese macaques. As such, RB is a candidate for a new behavioral tradition in this species.

Admixture in Humans of Two Divergent Plasmodium knowlesi Populations Associated with Different Macaque Host Species

PubMed Central

Divis, Paul C. S.; Singh, Balbir; Anderios, Fread; Hisam, Shamilah; Matusop, Asmad; Kocken, Clemens H.; Assefa, Samuel A.; Duffy, Craig W.; Conway, David J.

2015-01-01

Human malaria parasite species were originally acquired from other primate hosts and subsequently became endemic, then spread throughout large parts of the world. A major zoonosis is now occurring with Plasmodium knowlesi from macaques in Southeast Asia, with a recent acceleration in numbers of reported cases particularly in Malaysia. To investigate the parasite population genetics, we developed sensitive and species-specific microsatellite genotyping protocols and applied these to analysis of samples from 10 sites covering a range of >1,600 km within which most cases have occurred. Genotypic analyses of 599 P. knowlesi infections (552 in humans and 47 in wild macaques) at 10 highly polymorphic loci provide radical new insights on the emergence. Parasites from sympatric long-tailed macaques (Macaca fascicularis) and pig-tailed macaques (M. nemestrina) were very highly differentiated (FST = 0.22, and K-means clustering confirmed two host-associated subpopulations). Approximately two thirds of human P. knowlesi infections were of the long-tailed macaque type (Cluster 1), and one third were of the pig-tailed-macaque type (Cluster 2), with relative proportions varying across the different sites. Among the samples from humans, there was significant indication of genetic isolation by geographical distance overall and within Cluster 1 alone. Across the different sites, the level of multi-locus linkage disequilibrium correlated with the degree of local admixture of the two different clusters. The widespread occurrence of both types of P. knowlesi in humans enhances the potential for parasite adaptation in this zoonotic system. PMID:26020959

Acute Fetal Demise with First Trimester Maternal Infection Resulting from Listeria monocytogenes in a Nonhuman Primate Model

PubMed Central

Wolfe, Bryce; Wiepz, Gregory J.; Schotzko, Michele; Bondarenko, Gennadiy I.; Durning, Maureen; Simmons, Heather A.; Mejia, Andres; Faith, Nancy G.; Sampene, Emmanuel; Suresh, Marulasiddappa; Kathariou, Sophia; Czuprynski, Charles J.

2017-01-01

ABSTRACT Infection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy. Four pregnant cynomolgus macaques (Macaca fascicularis) received a single intragastric inoculation between days 36 and 46 of gestation with 107 CFU of an L. monocytogenes strain isolated from a previous cluster of human listeriosis cases that resulted in adverse pregnancy outcomes. Fecal shedding, maternal bacteremia, and fetal demise were consistently noted within 7 to 13 days. Biopsy specimens of maternal liver, spleen, and lymph node displayed variable inflammation and relatively low bacterial burden. In comparison, we observed greater bacterial burden in the decidua and placenta and the highest burden in fetal tissues. Histopathology indicated vasculitis, fibrinoid necrosis, and thrombosis of the decidual spiral arteries, acute chorioamnionitis and villitis in the placenta, and hematogenous infection of the fetus. Vascular pathology suggests early impact of L. monocytogenes infection on spiral arteries in the decidua, which we hypothesize precipitates subsequent placentitis and fetal demise. These results demonstrate that L. monocytogenes tropism for the maternal reproductive tract results in infection of the decidua, placenta, and the fetus itself during the first trimester of pregnancy. PMID:28223455

The mesencephalic reticular formation as a conduit for primate collicular gaze control: tectal inputs to neurons targeting the spinal cord and medulla.

PubMed

Perkins, Eddie; Warren, Susan; May, Paul J

2009-08-01

The superior colliculus (SC), which directs orienting movements of both the eyes and head, is reciprocally connected to the mesencephalic reticular formation (MRF), suggesting the latter is involved in gaze control. The MRF has been provisionally subdivided to include a rostral portion, which subserves vertical gaze, and a caudal portion, which subserves horizontal gaze. Both regions contain cells projecting downstream that may provide a conduit for tectal signals targeting the gaze control centers which direct head movements. We determined the distribution of cells targeting the cervical spinal cord and rostral medullary reticular formation (MdRF), and investigated whether these MRF neurons receive input from the SC by the use of dual tracer techniques in Macaca fascicularis monkeys. Either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin was injected into the SC. Wheat germ agglutinin conjugated horseradish peroxidase was placed into the ipsilateral cervical spinal cord or medial MdRF to retrogradely label MRF neurons. A small number of medially located cells in the rostral and caudal MRF were labeled following spinal cord injections, and greater numbers were labeled in the same region following MdRF injections. In both cases, anterogradely labeled tectoreticular terminals were observed in close association with retrogradely labeled neurons. These close associations between tectoreticular terminals and neurons with descending projections suggest the presence of a trans-MRF pathway that provides a conduit for tectal control over head orienting movements. The medial location of these reticulospinal and reticuloreticular neurons suggests this MRF region may be specialized for head movement control. (c) 2009 Wiley-Liss, Inc.

A central mesencephalic reticular formation projection to the Edinger-Westphal nuclei.

PubMed

May, Paul J; Warren, Susan; Bohlen, Martin O; Barnerssoi, Miriam; Horn, Anja K E

2016-11-01

The central mesencephalic reticular formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger-Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger-Westphal divisions receives synaptic input from the central mesencephalic reticular formation. Anterogradely labeled reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger-Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger-Westphal nucleus is not the primary target of the projection from the central mesencephalic reticular formation. We conclude from these data that the central mesencephalic reticular formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.

Anatomical evidence that the superior colliculus controls saccades through central mesencephalic reticular formation gating of omnipause neuron activity.

PubMed

Wang, Niping; Perkins, Eddie; Zhou, Lan; Warren, Susan; May, Paul J

2013-10-09

Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectum's saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC-cMRF-RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF.

A central mesencephalic reticular formation projection to the Edinger–Westphal nuclei

PubMed Central

May, Paul J.; Warren, Susan; Bohlen, Martin O.; Barnerssoi, Miriam

2016-01-01

The central mesencephalic reticular formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger–Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger–Westphal divisions receives synaptic input from the central mesencephalic reticular formation. Anterogradely labeled reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger–Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger–Westphal nucleus is not the primary target of the projection from the central mesencephalic reticular formation. We conclude from these data that the central mesencephalic reticular formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space. PMID:26615603

Absorbed Dose and Dose Equivalent Calculations for Modeling Effective Dose

NASA Technical Reports Server (NTRS)

Welton, Andrew; Lee, Kerry

2010-01-01

While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.

Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.

PubMed

Duong, Phuong-Anh; Little, Brent P

2014-08-01

Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations in the endometrium of rats, rabbits, and Macaca mulatta that received an implantation of copper/low-density polyethylene nanocomposite.

PubMed

Hu, Li-Xia; Wang, Hong; Rao, Meng; Zhao, Xiao-Ling; Yang, Jing; Hu, Shi-Fu; He, Jing; Xia, Wei; Liu, Hefang; Zhen, Bo; Di, Haihong; Xie, Changsheng; Xia, Xianping; Zhu, Changhong

2014-01-01

A copper/low-density polyethylene nanocomposite (nano-Cu/LDPE), a potential intrauterine device component material, has been developed from our research. A logical extension of our previous work, this study was conducted to investigate the expression of plasminogen activator inhibitor 1 (PAI-1), substance P (SP), and substance P receptor (SP-R) in the endometrium of Sprague Dawley rats, New Zealand White rabbits, and Macaca mulatta implanted with nano-Cu/LDPE composite. The influence of the nano-Cu/LDPE composite on the morphology of the endometrium was also investigated. Animals were randomly divided into five groups: the sham-operated control group (SO group), bulk copper group (Cu group), LDPE group, and nano-Cu/LDPE groups I and II. An expression of PAI-1, SP, and SP-R in the endometrial tissues was examined by immunohistochemistry at day 30, 60, 90, and 180 postimplantation. The significant difference for PAI-1, SP, and SP-R between the nano-Cu/LDPE groups and the SO group (P<0.05) was identified when the observation period was terminated, and the changes of nano-Cu/LDPE on these parameters were less remarkable than those of the Cu group (P<0.05). The damage to the endometrial morphology caused by the nano-Cu/LDPE composite was much less than that caused by bulk copper. The nano-Cu/LDPE composite might be a potential substitute for conventional materials for intrauterine devices in the future because of its decreased adverse effects on the endometrial microenvironment.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

PubMed Central

Rühm, Werner; Azizova, Tamara; Bouffler, Simon; Cullings, Harry M; Grosche, Bernd; Little, Mark P; Shore, Roy S; Walsh, Linda; Woloschak, Gayle E

2018-01-01

Abstract In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan. PMID:29432579

Elo-rating for Tracking Rank Fluctuations after Demographic Changes Involving Semi-free– ranging Rhesus Macaques (Macaca mulatta)

PubMed Central

Wooddell, Lauren J; Kaburu, Stefano SK; Suomi, Stephen J; Dettmer, Amanda M

2017-01-01

Rhesus macaques (Macaca mulatta) are gregarious primates that form despotic societies characterized by frequent and intense aggression. Within long-term social groups, demographic changes may influence hierarchical stability, potentially resulting in conflict and violently abrupt hierarchical changes. This conflict can result in serious implications for animal welfare, and thus, predictive tools would be invaluable to captive managers in determining social instabilities. Using the method Elo-rating to track rank changes and dominance stability, we predicted that demographic changes to a population of semi-free ranging rhesus macaques would result in changes in hierarchical stability. Over a 3 y period, dominance data were recorded on all troop members to track the hierarchy. Throughout the 3 y, significant changes occurred to the population (mainly due to health and colony management reasons; no changes specifically occurred for this study) including permanent removal of a large group of natal males, temporary and permanent removal of top-ranking females, and depositions of top-ranking families. Our retrospective study suggests that removing natal males was beneficial in promoting overall troop stability (that is, stability of dominance relationships), although remaining males opportunistically attempted to increase in rank, perhaps due to limited competition. Our results also suggest that removing top-ranking females, even temporarily, destabilized dominance relationships; consequently adjacently ranked females opportunistically increased in Elo-rating, both before and after the depositions of the α families. Thus, these challenges to the established hierarchy can be predicted by increases in Elo-rating within the β families after demographic changes to the α families. Our results suggest that the presence of natal males and the removal of top-ranking females should be minimized to maintain stable dominance relationships. In addition, longitudinal data

Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus)

PubMed Central

Levy, Xandria; Meints, Kerstin; Majolo, Bonaventura

2017-01-01

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 and distressed

Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus).

PubMed

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

Seventeen-year mortality experience of proton radiation in Macaca mulatta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yochmowitz, M.G.; Wood, D.H.; Salmon, Y.L.

1985-04-01

This is an interim report on the lifetime study of chronic mortality and its causes under investigation in 31 control (20 males, 11 females) and 217 survivors (124 males, 93 females) of an acute 90-day experiment in rhesus monkeys. Single acute whole-body exposures were made using 32-, 55-, 138-, 400-, and 2300-MeV protons in 1964-1965. Doses ranged from 25 to 800 rad and dose rates from 12.5 and 100 rad per minute. For pooled data: (1) mortality was signigicantly higher in irradiated animals (48%) than in controls (19%); (2) mortality in animals exposed to partially penetrating 55-MeV protons was essentiallymore » similar to those given totally penetrating 138-, 400-, and 2300-MeV exposures; (3) proton energies and doses that were effective in producing life shortening were greater than or equal to 55 MeV and greater than or equal to 360-400 rad, respectively; (4) death rates for irradiated animals compared to controls began to increase after approx.8 years, approx.2 years, and approx.1 year for those exposed to 360-400, 500-650, and 800 rad, respectively; (5) of the nine probable causes of death reported, the leading causes were primary infections in both irradiated and control animals, endometriosis, neoplasms, and organ degeneration; and (6) if endometriosis is included with the neoplastic group, deaths from all forms of neoplasms would be 42% in irradiated animals. From the results of this study, it is reasonable to conclude that development of endometriosis in females and neoplasms in males is enhanced significantly by proton irradiation over that of respective controls.« less

Implicit and Explicit Categorization: A Tale of Four Species

DTIC Science & Technology

2012-01-01

macaques (Macaca mulatta) and humans ( Homo sapiens ). J. Exp. Psychol. Anim. Behav. Process., 36, 54-65. Smith, J.D., Chapman, W.P., Redford, J.S...2010 (b). Stages of category learning in monkeys (Macaca mulatta) and humans ( Homo sapiens ). J. Exp. Psychol. Anim. Behav. Process., 36, 39-53...Smith, J.D., Coutinho, M.V.C., Couchman, J.J., 2011 (b). The learning of exclusive-or categories by monkeys (Macaca mulatta) and humans ( Homo sapiens ). J

[Evaluation of Organ Dose Estimation from Indices of CT Dose Using Dose Index Registry].

PubMed

Iriuchijima, Akiko; Fukushima, Yasuhiro; Ogura, Akio

Direct measurement of each patient organ dose from computed tomography (CT) is not possible. Most methods to estimate patient organ dose is using Monte Carlo simulation with dedicated software. However, dedicated software is too expensive for small scale hospitals. Not every hospital can estimate organ dose with dedicated software. The purpose of this study was to evaluate the simple method of organ dose estimation using some common indices of CT dose. The Monte Carlo simulation software Radimetrics (Bayer) was used for calculating organ dose and analysis relationship between indices of CT dose and organ dose. Multidetector CT scanners were compared with those from two manufactures (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare). Using stored patient data from Radimetrics, the relationships between indices of CT dose and organ dose were indicated as each formula for estimating organ dose. The accuracy of estimation method of organ dose was compared with the results of Monte Carlo simulation using the Bland-Altman plots. In the results, SSDE was the feasible index for estimation organ dose in almost organs because it reflected each patient size. The differences of organ dose between estimation and simulation were within 23%. In conclusion, our estimation method of organ dose using indices of CT dose is convenient for clinical with accuracy.

Late cataractogenesis caused by particulate radiations and photons in long-lived mammalian species

NASA Technical Reports Server (NTRS)

Lett, J. T.; Lee, A. C.; Cox, A. B.; Wood, D. H.

1989-01-01

Radiation cataractogenesis induced by small acute doses of particulate radiations and photons in the New Zealand white rabbit (Oryctolagus cuniculus), the beagle dog (Canis familiaris) and the rhesus monkey (Macaca mulatta) is discussed in the context of the use of animal models to assess the radiation hazards faced by humans during lengthy sojourns in deep space. Attention is paid to (1) the importance of lifespan studies with long-lived species - the above animals have median lifespans in captivity of 5-7, 13-14 and 25 years, respectively; and (2) the magnitudes of possible dose thresholds for cataractogenesis from sparsely ionizing radiations and the modifications of those thresholds by the late degenerative phase of the phenomenon.

Concentration of radiocesium in the wild Japanese monkey (Macaca fuscata) over the first 15 months after the Fukushima Daiichi nuclear disaster.

PubMed

Hayama, Shin-ichi; Nakiri, Sachie; Nakanishi, Setsuko; Ishii, Naomi; Uno, Taiki; Kato, Takuya; Konno, Fumiharu; Kawamoto, Yoshi; Tsuchida, Shuichi; Ochiai, Kazuhiko; Omi, Toshinori

2013-01-01

Following the massive earthquake that struck eastern Japan on March 11, 2011, a nuclear reactor core meltdown occurred at the Fukushima Daiichi Nuclear Power Plant, operated by Tokyo Electric Power Company, and was followed by the release of large amounts of radioactive materials. The objective of this study was to measure the concentration of radiocesium (134)Cs and (137)Cs in the muscle of Japanese monkeys (Macaca fuscata) inhabiting the forest area of Fukushima City and to determine the change in concentration over time as well as the relationship with the level of soil contamination. Cesium concentrations in the muscle of monkeys captured at locations with 100,000-300,000 Bq/m(2) were 6,000-25,000 Bq/kg in April 2011 and decreased over 3 months to around 1,000 Bq/kg. However, the concentration increased again to 2,000-3,000 Bq/kg in some animals during and after December 2011 before returning to 1,000 Bq/kg in April 2012, after which it remained relatively constant. This pattern of change in muscle radiocesium concentration was similar to that of the change in radiocesium concentration in atmospheric fallout. Moreover, the monkeys feed on winter buds and the cambium layer of tree bark potentially containing higher concentrations of radiocesium than that in the diet during the rest of the year. The muscle radiocesium concentration in the monkeys related significantly with the level of soil contamination at the capture locations.

Genetic characteristics and antimicrobial resistance of Escherichia coli from Japanese macaques (Macaca fuscata) in rural Japan.

PubMed

Ogawa, Keiko; Yamaguchi, Keiji; Suzuki, Masatsugu; Tsubota, Toshio; Ohya, Kenji; Fukushi, Hideto

2011-04-01

Escherichia coli was isolated from wild and captive Japanese macaques (Macaca fuscata) to investigate the risk of zoonotic infections and the prevalence of antimicrobial-resistant Escherichia coli in the wild macaque population in Shimokita Peninsula, a rural area of Japan. We collected 265 fresh fecal samples from wild macaques and 20 samples from captive macaques in 2005 and 2006 for E. coli isolation. The predominant isolates were characterized by serotyping, virulence gene profiling, plasmid profiling, pulsed-field gel electrophoresis (PFGE), and microbial sensitivity tests. In total, 248 E. coli strains were isolated from 159 fecal samples from wild macaques, and 42 E. coli were isolated from 17 samples from captive macaques. None of the virulence genes eae, stx, elt, and est were detected in any of the isolates. The relatedness between wild- and captive-derived isolates was low by serotyping, PFGE, and plasmid profiling. Serotypes O8:H6, O8:H34, O8:H42, O8:HUT, O103:H27, O103:HNM, and OUT:H27 were found in wild macaque feces; serotypes O157:H42 and O119:H21 were recovered from captive macaques. O-and H-serotypes of the 26 isolates were not typed by commercial typing antisera and were named OUT and HUT, respectively. Twenty-eight isolates had no flagellar antigen, and their H-serotypes were named HNM. Similarity of PFGE patterns between wild-derived isolates and captive-derived isolates was <70%. No plasmid profile was shared between wild-derived and captive-derived isolates. The prevalence of antimicrobial-resistant E. coli was 6.5% (n=62) in wild macaques, and these isolates were resistant to cephalothin. We conclude that wild Japanese macaques in Shimokita Peninsula were unlikely to act as a reservoir of pathogenic E. coli for humans and that antimicrobial-resistant E. coli in wild macaques may be derived from humans.

Alterations in the endometrium of rats, rabbits, and Macaca mulatta that received an implantation of copper/low-density polyethylene nanocomposite

PubMed Central

Hu, Li-Xia; Wang, Hong; Rao, Meng; Zhao, Xiao-Ling; Yang, Jing; Hu, Shi-Fu; He, Jing; Xia, Wei; Liu, Hefang; Zhen, Bo; Di, Haihong; Xie, Changsheng; Xia, Xianping; Zhu, Changhong

2014-01-01

A copper/low-density polyethylene nanocomposite (nano-Cu/LDPE), a potential intrauterine device component material, has been developed from our research. A logical extension of our previous work, this study was conducted to investigate the expression of plasminogen activator inhibitor 1 (PAI-1), substance P (SP), and substance P receptor (SP-R) in the endometrium of Sprague Dawley rats, New Zealand White rabbits, and Macaca mulatta implanted with nano-Cu/LDPE composite. The influence of the nano-Cu/LDPE composite on the morphology of the endometrium was also investigated. Animals were randomly divided into five groups: the sham-operated control group (SO group), bulk copper group (Cu group), LDPE group, and nano-Cu/LDPE groups I and II. An expression of PAI-1, SP, and SP-R in the endometrial tissues was examined by immunohistochemistry at day 30, 60, 90, and 180 postimplantation. The significant difference for PAI-1, SP, and SP-R between the nano-Cu/LDPE groups and the SO group (P<0.05) was identified when the observation period was terminated, and the changes of nano-Cu/LDPE on these parameters were less remarkable than those of the Cu group (P<0.05). The damage to the endometrial morphology caused by the nano-Cu/LDPE composite was much less than that caused by bulk copper. The nano-Cu/LDPE composite might be a potential substitute for conventional materials for intrauterine devices in the future because of its decreased adverse effects on the endometrial microenvironment. PMID:24596465

Age-related alterations of plasma glutathione and oxidation of redox potentials in chimpanzee (Pan troglodytes) and rhesus monkey (Macaca mulatta).

PubMed

Paredes, Jamespaul; Jones, Dean P; Wilson, Mark E; Herndon, James G

2014-04-01

Chimpanzee (Pan troglodytes) and rhesus macaque (Macaca mulatta) and humans (Homo sapiens) share physiological and genetic characteristics, but have remarkably different life spans, with chimpanzees living 50-60 % and the rhesus living 35-40 % of maximum human survival. Since oxidative processes are associated with aging and longevity, we might expect to see species differences in age-related oxidative processes. Blood and extracellular fluid contain two major thiol redox nodes, glutathione (GSH)/glutathione-disulfide (GSSG) and cysteine (Cys)/cystine (CySS), which are subject to reversible oxidation-reduction reactions and are maintained in a dynamic non-equilibrium state. Disruption of these thiol redox nodes leads to oxidation of their redox potentials (EhGSSG and EhCySS) which affects cellular physiology and is associated with aging and the development of chronic diseases in humans. The purpose of this study was to measure age-related changes in these redox thiols and their corresponding redox potentials (Eh) in chimpanzees and rhesus monkeys. Our results show similar age-related decreases in the concentration of plasma GSH and Total GSH as well as oxidation of the EhGSSG in male and female chimpanzees. Female chimpanzees and female rhesus monkeys also were similar in several outcome measures. For example, similar age-related decreases in the concentration of plasma GSH and Total GSH, as well as age-related oxidation of the EhGSSG were observed. The data collected from chimpanzees and rhesus monkeys corroborates previous reports on oxidative changes in humans and confirms their value as a comparative reference for primate aging.

The use of honey as a topical dressing to treat a large, devitalized wound in a stumptail macaque (Macaca arctoides).

PubMed

Staunton, Christine J; Halliday, Lisa C; Garcia, Kelly D

2005-07-01

There are many reasons wounds are managed as open wounds rather than by primary closure. Indications include gross contamination, infection, and skin loss leading to insufficient adjacent tissue for wound closure. The most common method of managing an open wound is with wet-to-dry dressings. Wet-to-dry dressings provide mechanical debridement and promote the movement of viscous exudates away from the wound. Wet-to-dry bandages ideally are changed every 12 to 24 h. For nonhuman primates, it is desirable to develop wound management techniques that limit animal handling for bandage changes and thus the frequency of sedation. Anecdotal reports on the use of honey to treat wounds date back to 2000 B.C. Recently, scientific inquiries have found merit to these reports. Honey accelerates healing because of its direct effects on tissue and antibacterial properties. In addition, dressings with honey can be changed relatively infrequently. Honey decreases inflammatory edema, hastens sloughing of devitalized tissue, attracts macrophages which cleanse the wound, provides a local cellular energy source, and protectively covers the wound. A high osmolarity, acidity, and hydrogen peroxide content confer honey with antibacterial properties. Here we describe the use of honey to manage a bite wound in a stumptail macaque (Macaca arctoides). The wound healed rapidly: after 2 weeks of treatment, there was markedly less exudate and no necrotic tissue. This report describes how honey may be helpful in the management of open wounds in nonhuman primates by minimizing the need for sedation for bandage changes.

Playing it cool: Characterizing social play, bout termination, and candidate play signals of juvenile and infant Tibetan macaques (Macaca thibetana).

PubMed

Wright, Kaitlin R; Mayhew, Jessica A; Sheeran, Lori K; Funkhouser, Jake A; Wagner, Ronald S; Sun, Li-Xing; Li, Jin-Hua

2018-07-18

Play behaviors and signals during playful interactions with juvenile conspecifics are important for both the social and cognitive development of young animals. The social organization of a species can also influence juvenile social play. We examined the relationships among play behaviors, candidate play signals, and play bout termination in Tibetan macaques (Macaca thibetana) during juvenile and infant social play to characterize the species play style. As Tibetan macaques are despotic and live in groups with strict linear dominance hierarchies and infrequent reconciliation, we predicted that play would be at risk of misinterpretation by both the individuals engaged in the play bout and by those watching, possibly leading to injury of the players. Animals living in such societies might need to frequently and clearly signal playful intent to play partners and other group members to avoid aggressive outcomes. We gathered video data on 21 individually-identified juvenile and infant macaques (one month to five years of age) from the Valley of the Wild Monkeys, Mt. Huangshan, China. We used all-occurrence sampling to record play behaviors and candidate play signals based on an ethogram. We predicted that play groups would use multiple candidate play signals in a variety of contexts and in association with the number of audience members in proximity to the players and play bout length. In the 283 playful interactions we scored, juvenile and infant macaques used multiple body and facial candidate play signals. Our data showed that juvenile and infant Tibetan macaques use a versatile repertoire of play behaviors and signals to sustain play.

Bioactive factors in milk across lactation: maternal effects and influence on infant growth in rhesus macaques (Macaca mulatta)

PubMed Central

Bernstein, Robin; Hinde, Katie

2017-01-01

Among mammals, numerous bioactive factors in milk vary across mothers and influence offspring outcomes. This emerging area of research has primarily investigated such dynamics within rodent biomedical models, domesticated dairy breeds, and among humans in clinical contexts. Less understood are signaling factors in the milk of non-human primates. Here, we report on multiple bioactive components in rhesus macaque (Macaca mulatta) milk and their associations with maternal and infant characteristics. Milk samples were collected from 59 macaques at multiple time points across lactation in conjunction with maternal and infant morphometrics and life-history animal records. Milk was assayed for adiponectin (APN), epidermal growth factor (EGF) and its receptor (EGF-R), and transforming growth factor beta 2 (TGF-β2). Regression models were constructed to assess the contributions of maternal factors on variation in milk bioactives, and on the relationship of this variation to infant body mass and growth. Maternal body mass, parity, social rank and infant sex were all predictive of concentrations of milk bioactives. Primiparous mothers produced milk with higher adiponectin, but lower EGF, than multiparous mothers. Heavier mothers produced milk with lower EGF and EGF-R, but higher TGF-β2. Mothers of daughters produced milk with higher TGF-β2. Mid-ranking mothers produced milk with higher mean EGF and adiponectin concentrations than low-ranking mothers. Milk EGF and EGF-R were positively associated with infant body mass and growth rate. Importantly, these signaling bioactives (APN, EGF, EGF-R, TGF-β2) were significantly correlated with nutritional values of milk. The effects of milk signals remained after controlling for the available energy in milk revealing the added physiological role of non-nutritive milk bioactives in the developing infant. Integrating analyses of energetic and other bioactive components of milk yields an important perspective for interpreting the

COMPARISON OF INTRAMUSCULAR FENTANYL-MIDAZOLAM, FENTANYL-MIDAZOLAM-KETAMINE, AND KETAMINE-MEDETOMIDINE FOR IMMOBILIZATION OF JAPANESE MACAQUES ( MACACA FUSCATA).

PubMed

Ølberg, Rolf-Arne; Sinclair, Melissa; Barker, Ian K; Crawshaw, Graham

2018-03-01

The combination of fentanyl and midazolam is commonly used as a sedative in humans. The objective of this study was to evaluate the sedative properties and physiological effects of fentanyl-midazolam and fentanyl-midazolam-ketamine compared with medetomidine-ketamine given intramuscularly in Japanese macaques ( Macaca fuscata). In a randomized crossover design, eight Japanese macaques were hand-injected with either 30 μg/kg fentanyl + 0.3 mg/kg midazolam (FM), 15 μg/kg fentanyl + 0.3 mg/kg midazolam + 5.0 mg/kg ketamine (FMK), or 0.05 mg/kg medetomidine + 5.0 mg/kg ketamine (MedK). Heart rate; indirect systolic, mean, and diastolic arterial pressure; respiratory rate; blood gas concentrations; rectal temperature; and duration of immobilization were recorded. Mixed linear models were used to evaluate the effects of drug treatment on all continuous variables, with a significance level of P < 0.05. Only three of seven animals receiving FM were successfully immobilized. All eight animals in both the FMK and MedK treatment groups had a rapid, smooth induction and were successfully immobilized. Both FMK and MedK treatments resulted in significant hypoxia and the animals required supplemental oxygen via face mask. The mean duration of FMK immobilization was 42 ± 10 min, significantly shorter than the 65 ± 14 min for the animals receiving MedK. Immobilization with MedK resulted in significantly lower heart rates, and significantly higher arterial pressure compared with FMK. Hypoventilation was significantly more pronounced in FMK-treated animals compared with MedK treatments. Immobilization with FMK resulted in a gradual, slow recovery whereas MedK-treated animals woke up more rapidly. Fentanyl-midazolam alone is not a useful sedative in Japanese macaques. A combination of fentanyl and midazolam with ketamine can be used as an alternative to medetomidine-ketamine in this species.

Radiation-induced endometriosis in Macaca mulatta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fanton, J.W.; Golden, J.G.

1991-05-01

Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, andmore » minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively.« less

A fully integrated wireless system for intracranial direct cortical stimulation, real-time electrocorticography data transmission, and smart cage for wireless battery recharge.

PubMed

Piangerelli, Marco; Ciavarro, Marco; Paris, Antonino; Marchetti, Stefano; Cristiani, Paolo; Puttilli, Cosimo; Torres, Napoleon; Benabid, Alim Louis; Romanelli, Pantaleo

2014-01-01

Wireless transmission of cortical signals is an essential step to improve the safety of epilepsy procedures requiring seizure focus localization and to provide chronic recording of brain activity for Brain Computer Interface (BCI) applications. Our group developed a fully implantable and externally rechargeable device, able to provide wireless electrocorticographic (ECoG) recording and cortical stimulation (CS). The first prototype of a wireless multi-channel very low power ECoG system was custom-designed to be implanted on non-human primates. The device, named ECOGIW-16E, is housed in a compact hermetically sealed Polyether ether ketone (PEEK) enclosure, allowing seamless battery recharge. ECOGIW-16E is recharged in a wireless fashion using a special cage designed to facilitate the recharge process in monkeys and developed in accordance with guidelines for accommodation of animals by Council of Europe (ETS123). The inductively recharging cage is made up of nylon and provides a thoroughly novel experimental setting on freely moving animals. The combination of wireless cable-free ECoG and external seamless battery recharge solves the problems and shortcomings caused by the presence of cables leaving the skull, providing a safer and easier way to monitor patients and to perform ECoG recording on primates. Data transmission exploits the newly available Medical Implant Communication Service band (MICS): 402-405 MHz. ECOGIW-16E was implanted over the left sensorimotor cortex of a macaca fascicularis to assess the feasibility of wireless ECoG monitoring and brain mapping through CS. With this device, we were able to record the everyday life ECoG signal from a monkey and to deliver focal brain stimulation with movement elicitation.

Impairment of ovarian function and associated health-related abnormalities are attributable to low social status in premenopausal monkeys and not mitigated by a high-isoflavone soy diet.

PubMed

Kaplan, J R; Chen, H; Appt, S E; Lees, C J; Franke, A A; Berga, S L; Wilson, M E; Manuck, S B; Clarkson, T B

2010-12-01

Psychological stress may impair premenopausal ovarian function and contribute to risk for chronic disease. Soy isoflavones may also influence ovarian function and affect health. Here, we report the effects of a psychological stressor (subordinate social status) and dietary soy on reproductive function and related health indices in female monkeys. We hypothesized that reproductive compromise and adverse health outcomes would be induced in subordinate when compared with dominant monkeys and be mitigated by exposure to soy. Subjects were 95 adult cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six. Animals consumed a soy-free, animal protein-based diet during an 8-month Baseline phase and then, during a 32-month Treatment phase, consumed either the baseline diet or an identical diet that substituted high-isoflavone soy protein for animal protein. Across more than 1200 menstrual cycles, subordinate monkeys consistently exhibited ovarian impairment [increased cycle length (P < 0.02) and variability (P < 0.02) and reduced levels of progesterone (P < 0.04) and estradiol (P < 0.04)]. Subordinate status was confirmed behaviorally and was associated with elevated cortisol (P < 0.04) and relative osteopenia (P < 0.05). Consumption of the soy diet had no significant effects. (i) Psychological stress adversely affects ovarian function and related health indices in a well-accepted animal model of women's health; (ii) Similar effects may extend to women experiencing reproductive impairment of psychogenic origin; (iii) soy protein and isoflavones neither exacerbate nor mitigate the effects of an adverse psychosocial environment; and (iv) this study was limited by an inability to investigate the genetic and developmental determinants of social status.

Cochlear Implant Electrode Array From Partial to Full Insertion in Non-Human Primate Model.

PubMed

Manrique-Huarte, Raquel; Calavia, Diego; Gallego, Maria Antonia; Manrique, Manuel

2018-04-01

To determine the feasibility of progressive insertion (two sequential surgeries: partial to full insertion) of an electrode array and to compare functional outcomes. 8 normal-hearing animals (Macaca fascicularis (MF)) were included. A 14 contact electrode array, which is suitably sized for the MF cochlea was partially inserted (PI) in 16 ears. After 3 months of follow-up revision surgery the electrode was advanced to a full insertion (FI) in 8 ears. Radiological examination and auditory testing was performed monthly for 6 months. In order to compare the values a two way repeated measures ANOVA was used. A p-value below 0.05 was considered as statistically significant. IBM SPSS Statistics V20 was used. Surgical procedure was completed in all cases with no complications. Mean auditory threshold shift (ABR click tones) after 6 months follow-up is 19 dB and 27 dB for PI and FI group. For frequencies 4, 6, 8, 12, and 16 kHz in the FI group, tone burst auditory thresholds increased after the revision surgery showing no recovery thereafter. Mean threshold shift at 6 months of follow- up is 19.8 dB ranging from 2 to 36dB for PI group and 33.14dB ranging from 8 to 48dB for FI group. Statistical analysis yields no significant differences between groups. It is feasible to perform a partial insertion of an electrode array and progress on a second surgical time to a full insertion (up to 270º). Hearing preservation is feasible for both procedures. Note that a minimal threshold deterioration is depicted among full insertion group, especially among high frequencies, with no statistical differences.

Genomic Sequencing and Characterization of Cynomolgus Macaque Cytomegalovirus▿

PubMed Central

Marsh, Angie K.; Willer, David O.; Ambagala, Aruna P. N.; Dzamba, Misko; Chan, Jacqueline K.; Pilon, Richard; Fournier, Jocelyn; Sandstrom, Paul; Brudno, Michael; MacDonald, Kelly S.

2011-01-01

Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (Macaca fascicularis; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development. PMID:21994460

Hydrogen and Oxygen Isotope Ratios in Body Water and Hair: Modeling Isotope Dynamics in Nonhuman Primates

PubMed Central

O’Grady, Shannon P.; Valenzuela, Luciano O.; Remien, Christopher H.; Enright, Lindsey E.; Jorgensen, Matthew J.; Kaplan, Jay R.; Wagner, Janice D.; Cerling, Thure E.; Ehleringer, James R.

2012-01-01

The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water (2H/1H, 18O/16O expressed as δ2H and δ18O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ2H and δ18O values of body water and a second model to predict the δ2H and δ18O values of hair. In contrast to previous human-based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ2H and δ18O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ2H and δ18O values of gut water and the 18O isotope fractionation associated with a carbonyl oxygen-water interaction in the gut (αow). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of αow was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems. PMID:22553163

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

PubMed Central

Ferrero, Enza; Orciani, Monia; Vacca, Paola; Ortolan, Erika; Crovella, Sergio; Titti, Fausto; Saccucci, Franca; Malavasi, Fabio

2004-01-01

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. PMID:15383153

Long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.

PubMed

Wang, B; Sun, G; Qiao, W; Liu, Y; Qiao, J; Ye, W; Wang, H; Wang, X; Lindquist, R; Wang, Y; Xiao, Y-F

2017-09-01

Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure. Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks. Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp. Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.

Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques.

PubMed

Phuah, Jiayao; Wong, Eileen A; Gideon, Hannah P; Maiello, Pauline; Coleman, M Teresa; Hendricks, Matthew R; Ruden, Rachel; Cirrincione, Lauren R; Chan, John; Lin, Philana Ling; Flynn, JoAnne L

2016-05-01

Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses against Mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model of M. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells in M. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response in M. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

PubMed

Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

2016-06-01

In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

A central mesencephalic reticular formation projection to medial rectus motoneurons supplying singly and multiply innervated extraocular muscle fibers.

PubMed

Bohlen, Martin O; Warren, Susan; May, Paul J

2017-06-01

We recently demonstrated a bilateral projection to the supraoculomotor area from the central mesencephalic reticular formation (cMRF), a region implicated in horizontal gaze changes. C-group motoneurons, which supply multiply innervated fibers in the medial rectus muscle, are located within the primate supraoculomotor area, but their inputs and function are poorly understood. Here, we tested whether C-group motoneurons in Macaca fascicularis monkeys receive a direct cMRF input by injecting this portion of the reticular formation with anterograde tracers in combination with injection of retrograde tracer into the medial rectus muscle. The results indicate that the cMRF provides a dense, bilateral projection to the region of the medial rectus C-group motoneurons. Numerous close associations between labeled terminals and each multiply innervated fiber motoneuron were present. Within the oculomotor nucleus, a much sparser ipsilateral projection onto some of the A- and B- group medial rectus motoneurons that supply singly innervated fibers was observed. Ultrastructural analysis demonstrated a direct synaptic linkage between anterogradely labeled reticular terminals and retrogradely labeled medial rectus motoneurons in all three groups. These findings reinforce the notion that the cMRF is a critical hub for oculomotility by proving that it contains premotor neurons supplying horizontal extraocular muscle motoneurons. The differences between the cMRF input patterns for C-group versus A- and B-group motoneurons suggest the C-group motoneurons serve a different oculomotor role than the others. The similar patterns of cMRF input to C-group motoneurons and preganglionic Edinger-Westphal motoneurons suggest that medial rectus C-group motoneurons may play a role in accommodation-related vergence. © 2017 Wiley Periodicals, Inc.

Survey of computed tomography scanners in Taiwan: Dose descriptors, dose guidance levels, and effective doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, H. Y.; Tung, C. J.; Yu, C. C.

2007-04-15

The IAEA and the ICRP recommended dose guidance levels for the most frequent computed tomography (CT) examinations to promote strategies for the optimization of radiation dose to CT patients. A national survey, including on-site measurements and questionnaires, was conducted in Taiwan in order to establish dose guidance levels and evaluate effective doses for CT. The beam quality and output and the phantom doses were measured for nine representative CT scanners. Questionnaire forms were completed by respondents from facilities of 146 CT scanners out of 285 total scanners. Information on patient, procedure, scanner, and technique for the head and body examinationsmore » was provided. The weighted computed tomography dose index (CTDI{sub w}), the dose length product (DLP), organ doses and effective dose were calculated using measured data, questionnaire information and Monte Carlo simulation results. A cost-effective analysis was applied to derive the dose guidance levels on CTDI{sub w} and DLP for several CT examinations. The mean effective dose{+-}standard deviation distributes from 1.6{+-}0.9 mSv for the routine head examination to 13{+-}11 mSv for the examination of liver, spleen, and pancreas. The surveyed results and the dose guidance levels were provided to the national authorities to develop quality control standards and protocols for CT examinations.« less

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Is Diet Flexibility an Adaptive Life Trait for Relictual and Peri-Urban Populations of the Endangered Primate Macaca sylvanus?

PubMed Central

Maibeche, Yasmina; Moali, Aissa; Yahi, Nassima; Menard, Nelly

2015-01-01

Habitat loss, fragmentation and urban expansion may drive some species to marginal habitats while others succeed in exploiting urban areas. Species that show dietary flexibility are more able to take advantage of human activities to supplement their diet with anthropogenically abundant and accessible resources. The Barbary macaque (Macaca sylvanus) is an endangered species due to the loss of its habitat, and human pressure. The population of Gouraya National Park (Algeria) lives in a relictual habitat that constitutes about 0.6% of the species range. In addition, this population is a unique case where urban expansion favours contact zones between Barbary macaque habitats and a big city (Bejaia). We quantified the dietary composition of Gouraya macaques over an annual cycle with the objective to understand how diet flexibility of this species may help it adapt to a relictual habitat or cope with urban expansion. We recorded the phenology of plant species every month. This study shows that Gouraya macaques, compared to those living in other forest types of the distribution area, are under lower seasonal constraints. They consume a greater amount of fruit and seeds that are available throughout much of the year, and a lesser amount of costly to find and extract subterranean foods. Therefore the Gouraya relictual habitat appears as a favourable environment compared to other major habitats of that species. This study also shows that colonizing peri-urban zones increases the availability and species richness of diet resources for Barbary macaques as they consume more human foods and exotic plants than in farther sites. Adult males eat more human foods than adult females and immatures do. The exploitation of high-energy anthropogenic food could favour macaque population growth and expansion towards the city center associated with human/macaque conflicts. We recommend applying management actions to restore macaques back to their natural habitat. PMID:25714476

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

PubMed

Bryan, J P; MacArthy, P; Rudock, A; Fogarty, J P; Dowd, H; Legters, L J; Perine, P L

1997-06-01

The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Temperature shapes coral-algal symbiosis in the South China Sea

NASA Astrophysics Data System (ADS)

Tong, Haoya; Cai, Lin; Zhou, Guowei; Yuan, Tao; Zhang, Weipeng; Tian, Renmao; Huang, Hui; Qian, Pei-Yuan

2017-01-01

With the increase in sea surface temperature (SST), scleractinian corals are exposed to bleaching threats but may possess certain flexibilities in terms of their associations with symbiotic algae. Previous studies have shown a close symbiosis between coral the and Symbiodinium; however, the spatial variation of the symbiosis and the attribution underlying are not well understood. In the present study, we examined coral-algal symbiosis in Galaxea fascicularis and Montipora spp. from three biogeographic regions across ~10° of latitude in the South China Sea. Analysis of similarities (ANOSIM) indicated a highly flexible coral-algal symbiosis in both G. fascicularis and Montipora spp. and canonical correspondence analysis (CCA) showed that temperature explained 83.2% and 60.1% of the explanatory subclade variations in G. fascicularis and Montipora spp., respectively, which suggested that temperature was the main environmental factor contributing to the diversity of Symbiodinium across the three regions. The geographic specificity of the Symbiodinium phylogeny was identified, revealing possible environmental selection across the three regions. These results suggest that scleractinian corals may have the ability to regulate Symbiodinium community structures under different temperatures and thus be able to adapt to gradual climate change.

Temperature shapes coral-algal symbiosis in the South China Sea

PubMed Central

Tong, Haoya; Cai, Lin; Zhou, Guowei; Yuan, Tao; Zhang, Weipeng; Tian, Renmao; Huang, Hui; Qian, Pei-Yuan

2017-01-01

With the increase in sea surface temperature (SST), scleractinian corals are exposed to bleaching threats but may possess certain flexibilities in terms of their associations with symbiotic algae. Previous studies have shown a close symbiosis between coral the and Symbiodinium; however, the spatial variation of the symbiosis and the attribution underlying are not well understood. In the present study, we examined coral-algal symbiosis in Galaxea fascicularis and Montipora spp. from three biogeographic regions across ~10° of latitude in the South China Sea. Analysis of similarities (ANOSIM) indicated a highly flexible coral-algal symbiosis in both G. fascicularis and Montipora spp. and canonical correspondence analysis (CCA) showed that temperature explained 83.2% and 60.1% of the explanatory subclade variations in G. fascicularis and Montipora spp., respectively, which suggested that temperature was the main environmental factor contributing to the diversity of Symbiodinium across the three regions. The geographic specificity of the Symbiodinium phylogeny was identified, revealing possible environmental selection across the three regions. These results suggest that scleractinian corals may have the ability to regulate Symbiodinium community structures under different temperatures and thus be able to adapt to gradual climate change. PMID:28084322

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

PubMed

Sosa, Sebastian; Zhang, Peng; Cabanes, Guénaël

2017-06-01

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

Dose gradient curve: A new tool for evaluating dose gradient.

PubMed

Sung, KiHoon; Choi, Young Eun

2018-01-01

Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

Dose gradient curve: A new tool for evaluating dose gradient

PubMed Central

Choi, Young Eun

2018-01-01

Purpose Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. Methods The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Results Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. Conclusions The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice. PMID:29698471

Long-term population survey of the Sulawesi black macaques (Macaca nigra) at Tangkoko Nature Reserve, North Sulawesi, Indonesia.

PubMed

Kyes, Randall C; Iskandar, Entang; Onibala, Jane; Paputungan, Umar; Laatung, Sylvia; Huettmann, Falk

2013-01-01

The Sulawesi black macaque (Macaca nigra) population at Tangkoko Nature Reserve in North Sulawesi, Indonesia has been the focus of periodic study for over 30 years. The population has shown considerable decline during much of that time. Here we present the results of a long-term population survey of the Tangkoko M. nigra, conducted over the past decade, to provide updated information and on-going assessment of the population. Line-transect sampling was conducted annually from 1999 to 2002 and 2005 to 2011 along the same transect during a 2- to 3-week survey period. Although further decline in the population was observed at the outset of the survey, over the subsequent 12-year period we have seen stability in the population parameters with evidence of modest increases in both group and population density. During the 1999-2002 survey periods, there was a mean group density of 3.6 groups/km(2) and a mean population density of 39.8 individuals/km(2) . During 2005-2011, mean group density increased to 3.8 groups/km(2) and mean population density was 51.4 individuals/km(2) . The 2011 survey data indicated an estimated group density of 4.3 groups/km(2) and a population density of 61.5 individuals/km(2) . Given that our transect was located in the core of the Tangkoko reserve, our density estimates should be limited to that area of the reserve. One explanation for the apparent stabilization of the population may be tied to the increasing and sustained number of training and research programs being conducted at the reserve. This collective effort by local and international groups may be helping to reduce illegal activity in the reserve (i.e., hunting and habitat destruction) and generate greater awareness of this critically endangered species. Without the continued vigilance afforded by the existing research and training programs and the support and involvement of the local people, the M. nigra at the Tangkoko Nature Reserve will likely face further decline. © 2012 Wiley

Bioactive factors in milk across lactation: Maternal effects and influence on infant growth in rhesus macaques (Macaca mulatta).

PubMed

Bernstein, Robin M; Hinde, Katie

2016-08-01

Among mammals, numerous bioactive factors in milk vary across mothers and influence offspring outcomes. This emerging area of research has primarily investigated such dynamics within rodent biomedical models, domesticated dairy breeds, and among humans in clinical contexts. Less understood are signaling factors in the milk of non-human primates. Here, we report on multiple bioactive components in rhesus macaque (Macaca mulatta) milk and their associations with maternal and infant characteristics. Milk samples were collected from 59 macaques at multiple time points across lactation in conjunction with maternal and infant morphometrics and life-history animal records. Milk was assayed for adiponectin (APN), epidermal growth factor (EGF) and its receptor (EGF-R), and transforming growth factor beta 2 (TGF-β2 ). Regression models were constructed to assess the contributions of maternal factors on variation in milk bioactives, and on the relationship of this variation to infant body mass and growth. Maternal body mass, parity, social rank, and infant sex were all predictive of concentrations of milk bioactives. Primiparous mothers produced milk with higher adiponectin, but lower EGF, than multiparous mothers. Heavier mothers produced milk with lower EGF and EGF-R, but higher TGF-β2 . Mothers of daughters produced milk with higher TGF-β2 . Mid-ranking mothers produced milk with higher mean EGF and adiponectin concentrations than low-ranking mothers. Milk EGF and EGF-R were positively associated with infant body mass and growth rate. Importantly, these signaling bioactives (APN, EGF, EGF-R, and TGF-β2 ) were significantly correlated with nutritional values of milk. The effects of milk signals remained after controlling for the available energy in milk revealing the added physiological role of non-nutritive milk bioactives in the developing infant. Integrating analyses of energetic and other bioactive components of milk yields an important perspective for interpreting

Mixed fortunes: ancient expansion and recent decline in population size of a subtropical montane primate, the Arunachal macaque Macaca munzala.

PubMed

Chakraborty, Debapriyo; Sinha, Anindya; Ramakrishnan, Uma

2014-01-01

Quaternary glacial oscillations are known to have caused population size fluctuations in many temperate species. Species from subtropical and tropical regions are, however, considerably less studied, despite representing most of the biodiversity hotspots in the world including many highly threatened by anthropogenic activities such as hunting. These regions, consequently, pose a significant knowledge gap in terms of how their fauna have typically responded to past climatic changes. We studied an endangered primate, the Arunachal macaque Macaca munzala, from the subtropical southern edge of the Tibetan plateau, a part of the Eastern Himalaya biodiversity hotspot, also known to be highly threatened due to rampant hunting. We employed a 534 bp-long mitochondrial DNA sequence and 22 autosomal microsatellite loci to investigate the factors that have potentially shaped the demographic history of the species. Analysing the genetic data with traditional statistical methods and advance Bayesian inferential approaches, we demonstrate a limited effect of past glacial fluctuations on the demographic history of the species before the last glacial maximum, approximately 20,000 years ago. This was, however, immediately followed by a significant population expansion possibly due to warmer climatic conditions, approximately 15,000 years ago. These changes may thus represent an apparent balance between that displayed by the relatively climatically stable tropics and those of the more severe, temperate environments of the past. This study also draws attention to the possibility that a cold-tolerant species like the Arunachal macaque, which could withstand historical climate fluctuations and grow once the climate became conducive, may actually be extremely vulnerable to anthropogenic exploitation, as is perhaps indicated by its Holocene ca. 30-fold population decline, approximately 3,500 years ago. Our study thus provides a quantitative appraisal of these demographically important

Dynamically accumulated dose and 4D accumulated dose for moving tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Heng; Li Yupeng; Zhang Xiaodong

2012-12-15

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose

DICOM organ dose does not accurately represent calculated dose in mammography

NASA Astrophysics Data System (ADS)

Suleiman, Moayyad E.; Brennan, Patrick C.; McEntee, Mark F.

2016-03-01

This study aims to analyze the agreement between the mean glandular dose estimated by the mammography unit (organ dose) and mean glandular dose calculated using Dance et al published method (calculated dose). Anonymised digital mammograms from 50 BreastScreen NSW centers were downloaded and exposure information required for the calculation of dose was extracted from the DICOM header along with the organ dose estimated by the system. Data from quality assurance annual tests for the included centers were collected and used to calculate the mean glandular dose for each mammogram. Bland-Altman analysis and a two-tailed paired t-test were used to study the agreement between calculated and organ dose and the significance of any differences. A total of 27,869 dose points from 40 centers were included in the study, mean calculated dose and mean organ dose (+/- standard deviation) were 1.47 (+/-0.66) and 1.38 (+/-0.56) mGy respectively. A statistically significant 0.09 mGy bias (t = 69.25; p<0.0001) with 95% limits of agreement between calculated and organ doses ranging from -0.34 and 0.52 were shown by Bland-Altman analysis, which indicates a small yet highly significant difference between the two means. The use of organ dose for dose audits is done at the risk of over or underestimating the calculated dose, hence, further work is needed to identify the causal agents for differences between organ and calculated doses and to generate a correction factor for organ dose.

Estimating thyroid dose in pediatric CT exams from surface dose measurement

NASA Astrophysics Data System (ADS)

Al-Senan, Rani; Mueller, Deborah L.; Hatab, Mustapha R.

2012-07-01

The purpose of this study was to investigate the possibility of estimating pediatric thyroid doses from CT using surface neck doses. Optically stimulated luminescence dosimeters were used to measure the neck surface dose of 25 children ranging in ages between one and three years old. The neck circumference for each child was measured. The relationship between obtained surface doses and thyroid dose was studied using acrylic phantoms of various sizes and with holes of different depths. The ratios of hole-to-surface doses were used to convert patients' surface dose to thyroid dose. ImPACT software was utilized to calculate thyroid dose after applying the appropriate age correction factors. A paired t-test was performed to compare thyroid doses from our approach and ImPACT. The ratio of thyroid to surface dose was found to be 1.1. Thyroid doses ranged from 20 to 80 mGy. Comparison showed no statistical significance (p = 0.18). In addition, the average of surface dose variation along the z-axis in helical scans was studied and found to range between 5% (in 10 cm diameter phantom/24 mm collimation/pitch 1.0) and 8% (in 16 cm diameter phantom/12 mm collimation/pitch 0.7). We conclude that surface dose is an acceptable predictor for pediatric thyroid dose from CT. The uncertainty due to surface dose variability may be reduced if narrower collimation is used with a pitch factor close to 1.0. Also, the results did not show any effect of thyroid depth on the measured dose.

The impact of inter-fraction dose variations on biological equivalent dose (BED): the concept of equivalent constant dose.

PubMed

Zavgorodni, S

2004-12-07

Inter-fraction dose fluctuations, which appear as a result of setup errors, organ motion and treatment machine output variations, may influence the radiobiological effect of the treatment even when the total delivered physical dose remains constant. The effect of these inter-fraction dose fluctuations on the biological effective dose (BED) has been investigated. Analytical expressions for the BED accounting for the dose fluctuations have been derived. The concept of biological effective constant dose (BECD) has been introduced. The equivalent constant dose (ECD), representing the constant physical dose that provides the same cell survival fraction as the fluctuating dose, has also been introduced. The dose fluctuations with Gaussian as well as exponential probability density functions were investigated. The values of BECD and ECD calculated analytically were compared with those derived from Monte Carlo modelling. The agreement between Monte Carlo modelled and analytical values was excellent (within 1%) for a range of dose standard deviations (0-100% of the dose) and the number of fractions (2 to 37) used in the comparison. The ECDs have also been calculated for conventional radiotherapy fields. The analytical expression for the BECD shows that BECD increases linearly with the variance of the dose. The effect is relatively small, and in the flat regions of the field it results in less than 1% increase of ECD. In the penumbra region of the 6 MV single radiotherapy beam the ECD exceeded the physical dose by up to 35%, when the standard deviation of combined patient setup/organ motion uncertainty was 5 mm. Equivalently, the ECD field was approximately 2 mm wider than the physical dose field. The difference between ECD and the physical dose is greater for normal tissues than for tumours.

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

PubMed

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

2015-10-01

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

Neutrons in active proton therapy: Parameterization of dose and dose equivalent.

PubMed

Schneider, Uwe; Hälg, Roger A; Lomax, Tony

2017-06-01

One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160MeV or 177MeV instead of 138MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy. Copyright © 2016. Published by Elsevier GmbH.

Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

PubMed

Norris, David C

2017-01-01

Background . Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent 'confirmatory' Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of 'the' maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as 'dose-finding', but as dose titration algorithm (DTA) -finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug's population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace 'the' MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to

The quantification of wound healing as a method to assess late radiation damage in primate skin exposed to high-energy protons

NASA Astrophysics Data System (ADS)

Cox, A. B.; Lett, J. T.

In an experiment examining the effects of space radiations on primates, different groups of rhesus monkeys (Macaca mulatta) were exposed to single whole-body doses of 32- or 55-MeV protons. Survivors of those exposures, together with age-matched controls, have been monitored continuously since 1964 and 1965. Late effects of nominal proton doses ranging from 2-6 Gray have been measured in vitro using skin fibroblasts from the animals. A logical extension of that study is reported here, and it involves observations of wound healing after 3-mm diameter dermal punches were removed from the ears (pinnae) of control and irradiated monkeys. Tendencies in the reduction of competence to repair cutaneous wound have been revealed by the initial examinations of animals that received doses greater than 2 Gy more than 2 decades earlier. These trends indicate that this method of assessing radiation damage to skin exposed to high-energy radiations warrants further study.

Studies on ’Macaca mulatta’ Infected with Rocky Mountain Spotted Fever

DTIC Science & Technology

1976-09-10

Mountain spotted fever (RMSF) rickettsiae. The LD50 in monkeys of the yolk-sac-grown seed stock was 10 to the 1.35th power plaque-forming units. Blood...acid glycoprotein, haptoglobin and albumin) were measured during a study in 16 male rhesus monkeys to determine the median lethal dose (LD50) of Rocky

A dose error evaluation study for 4D dose calculations

NASA Astrophysics Data System (ADS)

Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

2014-10-01

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

A dose error evaluation study for 4D dose calculations.

PubMed

Milz, Stefan; Wilkens, Jan J; Ullrich, Wolfgang

2014-11-07

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms.The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms.The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm; 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex programming

Lens capsule structure assessed with atomic force microscopy

PubMed Central

Sueiras, Vivian M.; Moy, Vincent T.

2015-01-01

Purpose To image the ultrastructure of the anterior lens capsule at the nanoscale level using atomic force microscopy (AFM). Methods Experiments were performed on anterior lens capsules maintained in their in situ location surrounding the lens from six human cadavers (donor age range: 44–88 years), four cynomolgus monkeys (Macaca fascicularis age range: 4.83–8.92 years), and seven pigs (<6 months). Hydration of all samples was maintained using Dulbecco’s Modified Eagle Medium (DMEM). Whole lenses were removed from the eye and placed anterior side up in agarose gel before gel hardening where only the posterior half of the lens was contained within the gel. After the gel hardened, the Petri dish was filled with DMEM until the point where the intact lens was fully submerged. AFM was used to image the anterior lens surface in contact mode. An integrated analysis program was used to calculate the interfibrillar spacing, fiber diameter, and surface roughness of the samples. Results The AFM images depict a highly ordered fibrous structure at the surface of the lens capsule in all three species. The interfibrillar spacing for the porcine, cynomolgus monkey, and human lens capsules was 0.68±0.25, 1.80±0.39, and 1.08±0.25 μm, respectively. In the primate, interfibrillar spacing significantly decreased linearly as a function of age. The fiber diameters ranged from 50 to 950 nm. Comparison of the root mean square (RMS) and average deviation demonstrate that the surface of the porcine lens capsule is the smoothest, and that the human and cynomolgus monkey capsules are significantly rougher. Conclusions AFM was successful in providing high-resolution images of the nanostructure of the lens capsule samples. Species-dependent differences were observed in the overall structure and surface roughness. PMID:25814829

Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training.

PubMed

Williams, N I; Helmreich, D L; Parfitt, D B; Caston-Balderrama, A; Cameron, J L

2001-11-01

Cross-sectional and short-term prospective studies in humans support the concept that low energy availability, and not other factors associated with exercise, causes the development of exercise-induced reproductive dysfunction. To rigorously test this hypothesis, we performed a longitudinal study, examining the role of low energy availability on both the development and the reversal of exercise-induced amenorrhea, using a monkey model (Macaca fascicularis). Eight adult female monkeys developed amenorrhea (defined as absence of menses for at least 100 d, with low and unchanging concentrations of LH, FSH, E2, and P4) after gradually increasing their daily exercise to 12.3 +/- 0.9 km/d of running over a 7- to 24-month period. Food intake remained constant during exercise training. To test whether amenorrhea is caused by low energy availability, four of the eight amenorrheic monkeys were provided with supplemental calories (138-181% of calorie intake during amenorrhea) while they maintained their daily training. All four monkeys exhibited increased reproductive hormone levels and reestablished ovulatory cycles, with recovery times for circulating gonadotropin levels ranging from 12-57 d from the initiation of supplemental feeding. The rapidity of recovery within the reproductive axis in a given monkey was directly related to the amount of energy that was consumed during the period of supplemental feeding (r = -0.97; P < 0.05). Repeated measurements of plasma T3 concentrations, a marker of cellular energy availability, revealed a tight correlation between the changes in reproductive function and T3 levels, such that T3 significantly decreased (27%) with the induction and significantly increased (18%) with the reversal of amenorrhea (P < 0.05). These data provide strong evidence that low energy availability plays a causal role in the development of exercise-induced amenorrhea.

Changes in Monkey Crystalline Lens Spherical Aberration During Simulated Accommodation in a Lens Stretcher

PubMed Central

Maceo Heilman, Bianca; Manns, Fabrice; de Castro, Alberto; Durkee, Heather; Arrieta, Esdras; Marcos, Susana; Parel, Jean-Marie

2015-01-01

Purpose. The purpose of this study was to quantify accommodation-induced changes in the spherical aberration of cynomolgus monkey lenses. Methods. Twenty-four lenses from 20 cynomolgus monkeys (Macaca fascicularis; 4.4–16.0 years of age; postmortem time 13.5 ± 13.0 hours) were mounted in a lens stretcher. Lens spherical aberration was measured in the unstretched (accommodated) and stretched (relaxed) states with a laser ray tracing system that delivered 51 equally spaced parallel rays along 1 meridian of the lens over the central 6-mm optical zone. A camera mounted below the lens was used to measure the ray height at multiple positions along the optical axis. For each entrance ray, the change in ray height with axial position was fitted with a third-order polynomial. The effective paraxial focal length and Zernike spherical aberration coefficients corresponding to a 6-mm pupil diameter were extracted from the fitted values. Results. The unstretched lens power decreased with age from 59.3 ± 4.0 diopters (D) for young lenses to 45.7 ± 3.1 D for older lenses. The unstretched lens shifted toward less negative spherical aberration with age, from −6.3 ± 0.7 μm for young lenses to −5.0 ± 0.5 μm for older lenses. The power and spherical aberration of lenses in the stretched state were independent of age, with values of 33.5 ± 3.4 D and −2.6 ± 0.5 μm, respectively. Conclusions. Spherical aberration is negative in cynomolgus monkey lenses and becomes more negative with accommodation. These results are in good agreement with the predicted values using computational ray tracing in a lens model with a reconstructed gradient refractive index. The spherical aberration of the unstretched lens becomes less negative with age. PMID:25670492

Changes in monkey crystalline lens spherical aberration during simulated accommodation in a lens stretcher.

PubMed

Maceo Heilman, Bianca; Manns, Fabrice; de Castro, Alberto; Durkee, Heather; Arrieta, Esdras; Marcos, Susana; Parel, Jean-Marie

2015-02-10

The purpose of this study was to quantify accommodation-induced changes in the spherical aberration of cynomolgus monkey lenses. Twenty-four lenses from 20 cynomolgus monkeys (Macaca fascicularis; 4.4-16.0 years of age; postmortem time 13.5 ± 13.0 hours) were mounted in a lens stretcher. Lens spherical aberration was measured in the unstretched (accommodated) and stretched (relaxed) states with a laser ray tracing system that delivered 51 equally spaced parallel rays along 1 meridian of the lens over the central 6-mm optical zone. A camera mounted below the lens was used to measure the ray height at multiple positions along the optical axis. For each entrance ray, the change in ray height with axial position was fitted with a third-order polynomial. The effective paraxial focal length and Zernike spherical aberration coefficients corresponding to a 6-mm pupil diameter were extracted from the fitted values. The unstretched lens power decreased with age from 59.3 ± 4.0 diopters (D) for young lenses to 45.7 ± 3.1 D for older lenses. The unstretched lens shifted toward less negative spherical aberration with age, from -6.3 ± 0.7 μm for young lenses to -5.0 ± 0.5 μm for older lenses. The power and spherical aberration of lenses in the stretched state were independent of age, with values of 33.5 ± 3.4 D and -2.6 ± 0.5 μm, respectively. Spherical aberration is negative in cynomolgus monkey lenses and becomes more negative with accommodation. These results are in good agreement with the predicted values using computational ray tracing in a lens model with a reconstructed gradient refractive index. The spherical aberration of the unstretched lens becomes less negative with age. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

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

PubMed

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

2017-06-01

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

The number of striatal cholinergic interneurons expressing calretinin is increased in parkinsonian monkeys.

PubMed

Petryszyn, Sarah; Di Paolo, Thérèse; Parent, André; Parent, Martin

2016-11-01

The most abundant interneurons in the primate striatum are those expressing the calcium-binding protein calretinin (CR). The present immunohistochemical study provides detailed assessments of their morphological traits, number, and topographical distribution in normal monkeys (Macaca fascicularis) and in monkeys rendered parkinsonian (PD) by MPTP intoxication. In primates, the CR+ striatal interneurons comprise small (8-12μm), medium (12-20μm) and large-sized (20-45μm) neurons, each with distinctive morphologies. The small CR+ neurons were 2-3 times more abundant than the medium-sized CR+ neurons, which were 20-40 times more numerous than the large CR+ neurons. In normal and PD monkeys, the density of small and medium-sized CR+ neurons was twice as high in the caudate nucleus than in the putamen, whereas the inverse occurred for the large CR+ neurons. Double immunostaining experiments revealed that only the large-sized CR+ neurons expressed choline acetyltransferase (ChAT). The number of large CR+ neurons was found to increase markedly (4-12 times) along the entire anteroposterior extent of both the caudate nucleus and putamen of PD monkeys compared to controls. Comparison of the number of large CR-/ChAT+ and CR+/ChAT+ neurons together with experiments involving the use of bromo-deoxyuridine (BrdU) as a marker of newly generated cells showed that it is the expression of CR by the large ChAT+ striatal interneurons, and not their absolute number, that is increased in the dopamine-depleted striatum. These findings reveal the modulatory role of dopamine in the phenotypic expression of the large cholinergic striatal neurons, which are known to play a crucial role in PD pathophysiology. Copyright © 2016 Elsevier Inc. All rights reserved.

Disulfide bond rearrangement during formation of the chorionic gonadotropin beta-subunit cystine knot in vivo.

PubMed

Wilken, Jason A; Bedows, Elliott

2004-05-04

The intracellular kinetic folding pathway of the human chorionic gonadotropin beta-subunit (hCG-beta) reveals the presence of a disulfide between Cys residues 38-57 that is not detected by X-ray analysis of secreted hCG-beta. This led us to propose that disulfide rearrangement is an essential feature of cystine knot formation during CG-beta folding. To test this, we used disulfide bond formation to monitor progression of intracellular folding intermediates of a previously uncharacterized protein, the CG-beta subunit of cynomolgous macaque (Macaca fascicularis). Like its human counterpart hCG-beta with which it shares 81% identity, macaque (m)CG-beta is a cystine knot-containing subunit that assembles with an alpha-subunit common to all glycoprotein hormone members of its species to form a biologically active heterodimer, mCG, which, like hCG, is required for pregnancy maintenance. An early mCG-beta folding intermediate, mpbeta1, contained two disulfide bonds, one between Cys34 and Cys88 and the other between Cys38 and Cys57. The subsequent folding intermediate, mpbeta2-early, was represented by an ensemble of folding forms that, in addition to the two disulfides mentioned above, included disulfide linkages between Cys9 and Cys57 and between Cys38 and Cys90. These latter two disulfides are those contained within the beta-subunit cystine knot and reveal that a disulfide exchange occurred during the mpbeta2-early folding step leading to formation of the mCG-beta knot. Thus, while defining the intracellular kinetic protein folding pathway of a monkey homologue of CG-beta, we detected the previously predicted disulfide exchange event crucial for CG-beta cystine knot formation and attainment of CG-beta assembly competence.

Müller glial cells of the primate foveola: An electron microscopical study.

PubMed

Syrbe, Steffen; Kuhrt, Heidrun; Gärtner, Ulrich; Habermann, Gunnar; Wiedemann, Peter; Bringmann, Andreas; Reichenbach, Andreas

2018-02-01

Previous studies on the ultrastructure of the primate foveola suggested the presence of an inverted cone-like structure which is formed by 25-35 specialized Müller cells overlying the area of high photoreceptor density. We investigated the ultrastructure of the Müller cells in the foveola of a human and macaque retina. Sections through the posterior poles of an eye of a 40 years-old human donor and an eye of an adult cynomolgus monkey (Macaca fascicularis) were investigated with transmission electron microscopy. The foveola consisted of an inner layer (thickness, 5.5-12 μm) which mainly contained somata (including nuclei) and inner processes of Müller cells; this layer overlaid the central Henle fibers and outer nuclear layer. The inner layer contained numerous watery cysts and thin lamelliform and tubular Müller cell processes which spread along the inner limiting membrane (ILM). The cytoplasm of the outer Müller cell processes became increasingly dispersed and electron-lucent in the course towards the outer limiting membrane. The ILM of the foveola was formed by a very thin basal lamina (thickness, <40 nm) while the basal lamina of the parafovea was thick (0.9-1 μm). The data show that there are various conspicuous features of foveolar Müller cells. The numerous thin Müller cell processes below the ILM may smooth the inner surface of the foveola (to minimize image distortion resulting from varying light refraction angles at an uneven retinal surface), create additional barriers to the vitreous cavity (compensating the thinness of the ILM), and provide mechanical stability to the tissue. The decreasing density of the outer process cytoplasm may support the optical function of the foveola. Copyright © 2017. Published by Elsevier Ltd.

Hydrogen and oxygen isotope ratios in body water and hair: modeling isotope dynamics in nonhuman primates.

PubMed

O'Grady, Shannon P; Valenzuela, Luciano O; Remien, Christopher H; Enright, Lindsey E; Jorgensen, Matthew J; Kaplan, Jay R; Wagner, Janice D; Cerling, Thure E; Ehleringer, James R

2012-07-01

The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water ((2)H/(1)H, (18)O/(16)O expressed as δ(2) H and δ(18)O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ(2)H and δ(18)O values of body water and a second model to predict the δ(2)H and δ(18)O values of hair. In contrast to previous human-based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ(2)H and δ(18)O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ(2)H and δ(18)O values of gut water and the (18)O isotope fractionation associated with a carbonyl oxygen-water interaction in the gut (α(ow)). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of α(ow) was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems. © 2012 Wiley Periodicals, Inc.

The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

PubMed Central

Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

2018-01-01

Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction.

PubMed

Bertin, Jonathan; Dury, Alain Y; Ouellet, Johanne; Pelletier, Georges; Labrie, Fernand

2014-08-01

To better understand the mechanisms underlying the beneficial effects of the intravaginal administration of dehydroepiandrosterone (DHEA) observed in postmenopausal women on sexual dysfunction. To identify the distribution of the androgen-synthesizing enzymes as well as androgen receptor (AR) and measure steroid levels in the monkey vagina. The cynomolgus monkey (Macaca fascicularis), the closest model to the human, has been used to measure the expression levels of steroidogenic enzymes and androgen receptor by quantitative reverse transcription polymerase chain reaction (n=4), confirmed by immunohistochemistry, and immunofluorescence (n=3). DHEA and its androgenic metabolites were quantified by LC-MS/MS (n=4). The presence of SRD5A1, SRD5A2, HSD17B3, AR as well as nerve fibers (PGP 9.5) was investigated, and steroid levels were measured. AR is widely distributed within the vaginal epithelium and also in the lamina propria with a lower expression in the muscularis layer and blood vessel walls. Androgen-forming enzymes, on the other hand, are expressed in the vaginal stratified squamous epithelium at a relatively high level where they are uniformly distributed from the basal membrane up to the superficial keratinized cells. The enzymes are at a lower level in blood vessel walls and zona muscularis where nerve fibers are localized. DHEA and its androgen metabolites are present at biologically significant concentrations in the monkey vagina. The enzymes responsible for androgen formation as well as AR are at the highest level in the superficial layer of the stratified epithelium and muscularis layers of the vagina. These data provide a potential explanation for the described role of androgens in regulating vaginal lubrication, smooth muscle activity, blood flow, and the neuronal activity potentially involved in the correction of sexual dysfunction. © 2014 International Society for Sexual Medicine.

Expression of the estrogen receptors and steroidogenic enzymes involved in estradiol formation in the monkey vagina.

PubMed

Bertin, Jonathan; Ouellet, Johanne; Dury, Alain Yves; Pelletier, Georges; Labrie, Fernand

2014-11-01

Estrogens are well recognized to have beneficial effects on vulvovaginal atrophy because of menopause. The distribution of estrogen receptors and enzymes responsible for estradiol (E2) formation within the vagina may provide insight into how dehydroepiandrosterone, a precursor of both estrogens and androgens, improves vulvovaginal atrophy. The purpose of the study was to determine where the steroidogenic enzymes responsible for E2 formation as well as estrogen receptors are localized in vaginal specimens collected from cynomolgus monkeys (Macaca fascicularis), the closest model to the human. HSD3B1, HSD17B1, HSD17B5, HSD17B12, aromatase (CYP19A1), estrogen receptor (ER)-α, and ER-β were measured or localized by quantitative real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence. Estrogens were quantified by liquid chromatography/tandem mass spectrometry. All steroidogenic enzymes and estrogen receptors are localized mainly in the superficial layer of the stratified squamous epithelium, blood vessel walls, and muscle fibers of the vagina. Immunolabeling of HSD17B5 and HSD17B12 shows that these enzymes are uniformly distributed from the basal membrane to the superficial keratinized cells, whereas HSD3B1 and aromatase are particularly localized in the outer (external) portion of the epithelial layer. ER-α and ER-β are also distributed within the vaginal epithelium, with expression especially elevated at the basal membrane level. The enzymes responsible for E2 formation as well as ERs are expressed mainly in the superficial layer of the stratified epithelium as well as the muscle layer of the vagina. The present data provide morphologic and biochemical support for the role of local dehydroepiandrosterone transformation into estrogens in regulating epithelial cell maturation, pH, fluid secretion, smooth muscle activity, and blood flow regulation in the primate vagina. Copyright © 2014 Elsevier Inc. All rights reserved.

The effect of age on the discriminative stimulus effects of ethanol and its GABA(A) receptor mediation in cynomolgus monkeys.

PubMed

Helms, Christa M; Grant, Kathleen A

2011-08-01

Excessive alcohol consumption is less common among aged compared to young adults, with aged adults showing greater sensitivity to many behavioral effects of ethanol. This study compared the discriminative stimulus effects of ethanol in young and middle-aged adult cynomolgus monkeys (Macaca fascicularis) and its γ-aminobutyric acid (GABA)(A) receptor mediation. Two male and two female monkeys trained to discriminate ethanol (1.0 g/kg, i.g.; 60-min pre-treatment interval) from water at 5-6 years of age (Grant et al. in Psychopharmacology 152:181-188, 2000) were re-trained in the current study more than a decade later (19.3 ± 1.0 years of age) for a within-subjects comparison. Also, four experimentally naïve middle-aged (mean ± SEM, 17.0 ± 1.5 years of age) female monkeys were trained to discriminate ethanol for between-subjects comparison with published data from young adult naïve monkeys. Two of the naïve middle-aged monkeys attained criterion performance, with weak stimulus control and few discrimination tests, despite greater blood-ethanol concentration 60 min after 1.0 g/kg ethanol in middle-aged compared to young adult female monkeys (Green et al. in Alcohol Clin Exp Res 23:611-616, 1999). The efficacy of the GABA(A) receptor positive modulators pentobarbital, midazolam, allopregnanolone, pregnanolone, and androsterone to substitute for the discriminative stimulus effects of 1.0 g/kg ethanol was maintained from young adulthood to middle age. The data suggest that 1.0 g/kg ethanol is a weak discriminative stimulus in naive middle-aged monkeys. Nevertheless, the GABA(A) receptor mechanisms mediating the discriminative stimulus effects of ethanol, when learned as a young adult, appear stable across one third of the primate lifespan.

Intracanal bisphosphonate does not inhibit replacement resorption associated with delayed replantation of monkey incisors.

PubMed

Thong, Yo Len; Messer, Harold H; Zain, Rosnah Binti; Saw, Lip Hean; Yoong, Lai Thong

2009-08-01

Progressive replacement resorption following delayed replantation of avulsed teeth has proved to be an intractable clinical problem. A wide variety of therapeutic approaches have failed to result in the predictable arrest of resorption, with a good long-term prognosis for tooth survival. Bisphosphonates are used in the medical management of a range of bone disorders and topically applied bisphosphonate has been reported to inhibit root resorption in dogs. This study evaluated the effectiveness of a bisphosphonate (etidronate disodium) as an intracanal medicament in the root canals of avulsed monkey teeth, placed before replantation after 1 h of extraoral dry storage. Incisors of six Macaca fascicularis monkeys were extracted and stored dry for 1 h. Teeth were then replanted after canal contamination with dental plaque (negative control) or after root canal debridement and placement of etidronate sealed in the canal space. A positive control of calcium hydroxide placed 8-9 days after replantation was also included. All monkeys were sacrificed 8 weeks later and block sections were prepared for histomorphometric assessment of root resorption and periodontal ligament status. Untreated teeth showed the greatest extent of root resorption (46% of the root surface), which was predominantly inflammatory in nature. Calcium hydroxide treated teeth showed the lowest overall level of resorption (<30% of the root surface), while the bisphosphonate-treated group was intermediate (39%). Ankylosis, defined as the extent of the root surface demonstrating direct bony union to both intact and resorbed root surface, was the lowest in the untreated control group (15% of the root surface), intermediate in the calcium hydroxide group (27%) and the highest in the bisphosphonate group (41%). Bony attachment to the tooth root was divided approximately equally between attachment to intact cementum and to previously resorbed dentin. Overall, bisphosphonate resulted in a worse outcome than

On the Role of the Pedunculopontine Nucleus and Mesencephalic Reticular Formation in Locomotion in Nonhuman Primates.

PubMed

Goetz, Laurent; Piallat, Brigitte; Bhattacharjee, Manik; Mathieu, Hervé; David, Olivier; Chabardès, Stéphan

2016-05-04

The mesencephalic reticular formation (MRF) is formed by the pedunculopontine and cuneiform nuclei, two neuronal structures thought to be key elements in the supraspinal control of locomotion, muscle tone, waking, and REM sleep. The role of MRF has also been advocated in modulation of state of arousal leading to transition from wakefulness to sleep and it is further considered to be a main player in the pathophysiology of gait disorders seen in Parkinson's disease. However, the existence of a mesencephalic locomotor region and of an arousal center has not yet been demonstrated in primates. Here, we provide the first extensive electrophysiological mapping of the MRF using extracellular recordings at rest and during locomotion in a nonhuman primate (NHP) (Macaca fascicularis) model of bipedal locomotion. We found different neuronal populations that discharged according to a phasic or a tonic mode in response to locomotion, supporting the existence of a locomotor neuronal circuit within these MRF in behaving primates. Altogether, these data constitute the first electrophysiological characterization of a locomotor neuronal system present within the MRF in behaving NHPs under normal conditions, in accordance with several studies done in different experimental animal models. We provide the first extensive electrophysiological mapping of the two major components of the mesencephalic reticular formation (MRF), namely the pedunculopontine and cuneiform nuclei. We exploited a nonhuman primate (NHP) model of bipedal locomotion with extracellular recordings in behaving NHPs at rest and during locomotion. Different MRF neuronal groups were found to respond to locomotion, with phasic or tonic patterns of response. These data constitute the first electrophysiological evidences of a locomotor neuronal system within the MRF in behaving NHPs. Copyright © 2016 the authors 0270-6474/16/364917-13$15.00/0.

Superficial dose evaluation of four dose calculation algorithms

NASA Astrophysics Data System (ADS)

Cao, Ying; Yang, Xiaoyu; Yang, Zhen; Qiu, Xiaoping; Lv, Zhiping; Lei, Mingjun; Liu, Gui; Zhang, Zijian; Hu, Yongmei

2017-08-01

Accurate superficial dose calculation is of major importance because of the skin toxicity in radiotherapy, especially within the initial 2 mm depth being considered more clinically relevant. The aim of this study is to evaluate superficial dose calculation accuracy of four commonly used algorithms in commercially available treatment planning systems (TPS) by Monte Carlo (MC) simulation and film measurements. The superficial dose in a simple geometrical phantom with size of 30 cm×30 cm×30 cm was calculated by PBC (Pencil Beam Convolution), AAA (Analytical Anisotropic Algorithm), AXB (Acuros XB) in Eclipse system and CCC (Collapsed Cone Convolution) in Raystation system under the conditions of source to surface distance (SSD) of 100 cm and field size (FS) of 10×10 cm2. EGSnrc (BEAMnrc/DOSXYZnrc) program was performed to simulate the central axis dose distribution of Varian Trilogy accelerator, combined with measurements of superficial dose distribution by an extrapolation method of multilayer radiochromic films, to estimate the dose calculation accuracy of four algorithms in the superficial region which was recommended in detail by the ICRU (International Commission on Radiation Units and Measurement) and the ICRP (International Commission on Radiological Protection). In superficial region, good agreement was achieved between MC simulation and film extrapolation method, with the mean differences less than 1%, 2% and 5% for 0°, 30° and 60°, respectively. The relative skin dose errors were 0.84%, 1.88% and 3.90%; the mean dose discrepancies (0°, 30° and 60°) between each of four algorithms and MC simulation were (2.41±1.55%, 3.11±2.40%, and 1.53±1.05%), (3.09±3.00%, 3.10±3.01%, and 3.77±3.59%), (3.16±1.50%, 8.70±2.84%, and 18.20±4.10%) and (14.45±4.66%, 10.74±4.54%, and 3.34±3.26%) for AXB, CCC, AAA and PBC respectively. Monte Carlo simulation verified the feasibility of the superficial dose measurements by multilayer Gafchromic films. And the rank

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce;

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

PubMed Central

Adams Waldorf, Kristina M.; Gravett, Michael G.; McAdams, Ryan M.; Paolella, Louis J.; Gough, G. Michael; Carl, David J.; Bansal, Aasthaa; Liggitt, H. Denny; Kapur, Raj P.; Reitz, Frederick B.; Rubens, Craig E.

2011-01-01

Background Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. Methodology/Principal Findings Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. Conclusions/Significance A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently

The Organization of Collective Group Movements in Wild Barbary Macaques (Macaca sylvanus): Social Structure Drives Processes of Group Coordination in Macaques

PubMed Central

Seltmann, Anne; Majolo, Bonaventura

2013-01-01

Social animals have to coordinate activities and collective movements to benefit from the advantages of group living. Animals in large groups maintain cohesion by self-organization processes whereas in smaller groups consensus decisions can be reached. Where consensus decisions are relevant leadership may emerge. Variation in the organization of collective movements has been linked to variation in female social tolerance among macaque species ranging from despotic to egalitarian. Here we investigated the processes underlying group movements in a wild macaque species characterized by a degree of social tolerance intermediate to previously studied congeneric species. We focused on processes before, during and after the departure of the first individual. To this end, we observed one group of wild Barbary macaques (Macaca sylvanus) in the Middle Atlas, Morocco using all-occurrence behaviour sampling of 199 collective movements. We found that initiators of a collective movement usually chose the direction in which more individuals displayed pre-departure behavior. Dominant individuals contributed to group movements more than subordinates, especially juveniles, measured as frequencies of successful initiations and pre-departure behaviour. Joining was determined by affiliative relationships and the number of individuals that already joined the movement (mimetism). Thus, in our study group partially shared consensus decisions mediated by selective mimetism seemed to be prevalent, overall supporting the suggestion that a species’ social style affects the organization of group movements. As only the most tolerant species show equally shared consensus decisions whereas in others the decision is partially shared with a bias to dominant individuals the type of consensus decisions seems to follow a stepwise relation. Joining order may also follow a stepwise, however opposite, relationship, because dominance only determined joining in highly despotic, but not in intermediate

GENERAL CONSIDERATIONS OF DOSE-EFFECT AND DOSE-RESPONSE RELATIONSHIPS

EPA Science Inventory

ABSTRACT In 2003, the International Union of Pure and Applied chemistry (IUPAC) issued a glossary of terms that included the defi nition of dose-effect and doseresponse relationships (Nordberg et al., 2004). Dose effect relationship is defined as an association between dose and...

198 AAAAI Survey on Immunotherapy Practice Patterns Concerning Dosing, Dose-Adjustment after Missed Doses and Duration of Immunotherapy

PubMed Central

Linnemann, Désirée Larenas; Gupta, Payel; Mithani, Sima; Ponda, Punita

2012-01-01

Background Several practical issues dealing with the exact application of allergen immunotherapy (AIT) among European and US allergists are not well known. Guidelines on AIT give recommendations and suggestions for only some of them. We present this unique survey with worldwide response. Methods The AAAAI immunotherapy committee conducted a web-based practice patterns survey (program: Survey Monkey) among all members in&outside US on dosing, dose-adjustment after missed doses and duration of AIT. Results 1201 Returned questionnaires (almost 25% response rate). 21% were non-US-Canada members. Maintenance doses in USCan are (mean/median): Dermatophagoides farinae (Df) combined with Dermatophagoides pteronyssinus (Dpt): 2155/1000AU; Df solo 2484/1000AU. Dpt when combined with Df 1937/1000AU; Dpt solo: 2183/1000AU.Cat 3224/2000BAU. Grass 11,410/4000BAU. 57-65% of the dosing falls within the recommended Practice Parameters recommended ranges. Non-USCan allergists expressed maintenance doses in many different units making analysis impossible. Dose-adjustment after missed doses is based on ‘time elapsed since the last applied dose’ by 77% of USCan and 58% of non-USCan allergists and on ‘time since missed scheduled dose’ by the rest. Doses are adjusted when a patient comes in more than 14 d/5 wk after the last administration at build-up/maintenance by both USCan and non-USCan colleagues. The mostly followed dose-adjustment schedules after 1, 2, 3 missed doses are: Build-up: repeat last dose, reduce by one dose, reduce by 2 doses; maintenance: reduce by one dose, reduce by 2 doses, reduce by 3 doses. 26% uses a different approach reducing doses by a certain percentage or volume. AIT is restarted after a gap in build-up of >30 days and of >12 weeks during maintenance in both groups (median). Outside USCan AIT is prescribed for 3 years (Median). However, 75% of USCan allergists prescribes AIT for 5 years. Main reasons why to continue AIT beyond 5 years: �

Co-localization of glycine and gaba immunoreactivity in interneurons in Macaca monkey cerebellar cortex.

PubMed

Crook, J; Hendrickson, A; Robinson, F R

2006-09-15

Previous work demonstrates that the cerebellum uses glycine as a fast inhibitory neurotransmitter [Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66(1):211-221; Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450(1-2):342-353; Dieudonne S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. Proc Natl Acad Sci U S A 92:1441-1445; Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057; Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498; Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM (2005) Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 482(2):123-141]. In the rat cerebellum glycine is not released by itself but is released together with GABA by Lugaro cells onto Golgi cells [Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057] and by Golgi cells onto unipolar brush and granule cells [Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498]. Here we report, from immunolabeling evidence in Macaca cerebellum, that interneurons in the granular cell layer are glycine+ at a density

Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials

PubMed Central

Norris, David C.

2017-01-01

Background. Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent ‘confirmatory’ Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of ‘the’ maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as ‘dose-finding’, but as dose titration algorithm (DTA)-finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug’s population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace ‘the’ MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically

Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta).

PubMed

Dow, Geoffrey S; Gettayacamin, Montip; Hansukjariya, Pranee; Imerbsin, Rawiwan; Komcharoen, Srawuth; Sattabongkot, Jetsumon; Kyle, Dennis; Milhous, Wilbur; Cozens, Simon; Kenworthy, David; Miller, Anne; Veazey, Jim; Ohrt, Colin

2011-07-29

Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns. In 2005, the radical curative efficacy of tafenoquine combinations was investigated in Plasmodium cynomolgi-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD). In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans. The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg versus 18 mg/kg) than for monotherapy. This regimen (1.8 mg/kg) was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg) was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg) appears to be biologically equivalent to a 600-1200 mg dose in humans. At

Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta)

PubMed Central

2011-01-01

Background Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns. Methods In 2005, the radical curative efficacy of tafenoquine combinations was investigated in Plasmodium cynomolgi-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD). In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans. Results The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg versus 18 mg/kg) than for monotherapy. This regimen (1.8 mg/kg) was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg) was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg) appears to be biologically equivalent to a 600

Interferons and Alphavirus Pathogenesis: Implications for Developing Medical Countermeasures

DTIC Science & Technology

2005-12-01

respiratory tract with Venezuelan equine encephalomyelitis virus in normal and operated Macaca rhesus monkeys. II. Results of histological examination... respiratory tract with Venezuelan equine encephalomyelitis virus in normal and operated Macaca rhesus monkeys. I. Results of virological examination. Acta...alphavirus family: Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV). I

Accuracy of Human and Veterinary Point-of-Care Glucometers for Use in Rhesus Macaques (Macaca mulatta), Sooty Mangabeys (Cercocebus atys), and Chimpanzees (Pan troglodytes).

PubMed

Clemmons, Elizabeth A; Stovall, Melissa I; Owens, Devon C; Scott, Jessica A; Jones-Wilkes, Amelia C; Kempf, Doty J; Ethun, Kelly F

2016-01-01

Handheld, point-of-care glucometers are commonly used in NHP for clinical and research purposes, but whether these devices are appropriate for use in NHP is unknown. Other animal studies indicate that glucometers should be species-specific, given differences in glucose distribution between RBC and plasma; in addition, Hct and sampling site (venous compared with capillary) influence glucometer readings. Therefore, we compared the accuracy of 2 human and 2 veterinary glucometers at various Hct ranges in rhesus macaques (Macaca mulatta), sooty mangabeys (Cercocebus atys), and chimpanzees (Pan troglodytes) with that of standard laboratory glucose analysis. Subsequent analyses assessed the effect of hypoglycemia, hyperglycemia, and sampling site on glucometer accuracy. The veterinary glucometers overestimated blood glucose (BG) values in all species by 26 to 75 mg/dL. The mean difference between the human glucometers and the laboratory analyzer was 7 mg/dL or less in all species. The human glucometers overestimated BG in hypoglycemic mangabeys by 4 mg/dL and underestimated BG in hyperglycemic mangabeys by 11 mg/dL; similar patterns occurred in rhesus macaques. Hct did not affect glucometer accuracy, but all samples were within the range at which glucometers generally are accurate in humans. BG values were significantly lower in venous than capillary samples. The current findings show that veterinary glucometers intended for companion-animal species are inappropriate for use in the studied NHP species, whereas the human glucometers showed clinically acceptable accuracy in all 3 species. Finally, potential differences between venous and capillary BG values should be considered when comparing and evaluating results.

Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model.

PubMed

Jaikuna, Tanwiwat; Khadsiri, Phatchareewan; Chawapun, Nisa; Saekho, Suwit; Tharavichitkul, Ekkasit

2017-02-01

To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD 2 ) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD 2 verification with pair t -test statistical analysis using IBM SPSS Statistics version 22 (64-bit). Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D 90% , 0.56% in the bladder, 1.74% in the rectum when determined by D 2cc , and less than 1% in Pinnacle. The difference in the EQD 2 between the software calculation and the manual calculation was not significantly different with 0.00% at p -values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

PubMed Central

Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

2012-01-01

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778