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Sample records for humans monkeys exposed

  1. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

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    Borie Dominic C

    2006-03-01

    Full Text Available Abstract Background The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose α (1,3 galactose (αGal present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s with bioartficial liver devices (BALs, composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine αGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (VH immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgVH genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. Results Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the VH3 family, with a minor contribution from the VH4 family. Immunoglobulin heavy-chain gene (VH cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, VH3-11cyno, has

  2. Vicarious Learning from Human Models in Monkeys

    OpenAIRE

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

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

  3. Vicarious learning from human models in monkeys.

    Science.gov (United States)

    Falcone, Rossella; Brunamonti, Emiliano; Genovesio, Aldo

    2012-01-01

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

  4. Vicarious learning from human models in monkeys.

    Directory of Open Access Journals (Sweden)

    Rossella Falcone

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

  5. Steroid metabolism by monkey and human spermatozoa

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    DEFF Research Database (Denmark)

    Catani, Marco; Robertsson, Naianna; Beyh, Ahmad

    2017-01-01

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

  7. Comparison of Object Recognition Behavior in Human and Monkey

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    Rajalingham, Rishi; Schmidt, Kailyn

    2015-01-01

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

  8. Responsiveness in Behaving Monkeys and Human Subjects

    Science.gov (United States)

    1993-07-31

    Status of Current Research - Statement of Work Each study involving awake , behaving monkey neurophysiological recording used a behavioral paradigm that...anesthesia. A craniotomy was performed at approximately A+ 14.5mm. The recording chamber then was fixed to the skull at a lateral angle of 8’ from

  9. Morphofunctional lesions in kidneys of monkeys pretreated with drugs and exposed to proton radiation

    International Nuclear Information System (INIS)

    Fedorenko, B.S.; Kabachenko, A.N.; Smirnova, O.A.

    1980-01-01

    A study was made of the effect of adeturon or complex treatment on the development of structural derangements, the volume of renal glomeruli and Bowman's capsules in kidneys of monkeys exposed to 240 MeV protons in a dosage of 700 rad. Injection or adeturon (100 mg/kg) 15 min before irradiation, or treatment with antibiotics and vitamins fail to lower the degree of morphological damage to kidneys. It is assumed that processes of autosensitization in the irradiated animal organism play an important role in the development of radiation injury to kidneys

  10. GLP-1 receptor localization in monkey and human tissue

    DEFF Research Database (Denmark)

    Pyke, Charles; Heller, R Scott; Kirk, Rikke K

    2014-01-01

    and increase heart rate. Using a new monoclonal antibody for immunohistochemistry, we detected GLP-1 receptor (GLP-1R) in important target organs in humans and monkeys. In the pancreas, GLP-1R was predominantly localized in β-cells with a markedly weaker expression in acinar cells. Pancreatic ductal epithelial...

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

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

    2014-01-01

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

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

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    Rhia eCatapano

    2014-12-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. The nucleus pararaphales in the human, chimpanzee, and macaque monkey.

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    Baizer, Joan S; Weinstock, Nadav; Witelson, Sandra F; Sherwood, Chet C; Hof, Patrick R

    2013-03-01

    The human cerebral cortex and cerebellum are greatly expanded compared to those of other mammals, including the great apes. This expansion is reflected in differences in the size and organization of precerebellar brainstem structures, such as the inferior olive. In addition, there are cell groups unique to the human brainstem. One such group may be the nucleus pararaphales (PRa); however, there is disagreement among authors about the size and location of this nucleus in the human brainstem. The name "pararaphales" has also been used for neurons in the medulla shown to project to the flocculus in the macaque monkey. We have re-examined the existence and status of the PRa in eight humans, three chimpanzees, and four macaque monkeys using Nissl-stained sections as well as immunohistochemistry. In the human we found a cell group along the midline of the medulla in all cases; it had the form of interrupted cell columns and was variable among cases in rostrocaudal and dorsoventral extent. Cells and processes were highly immunoreactive for non-phosphorylated neurofilament protein (NPNFP); somata were immunoreactive to the synthetic enzyme for nitric oxide, nitric oxide synthase, and for calretinin. In macaque monkey, there was a much smaller oval cell group with NPNFP immunoreactivity. In the chimpanzee, we found a region of NPNFP-immunoreactive cells and fibers similar to what was observed in macaques. These results suggest that the "PRa" in the human may not be the same structure as the flocculus-projecting cell group described in the macaque. The PRa, like the arcuate nucleus, therefore may be unique to humans.

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

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

    2015-05-01

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

  16. Tetraploidy in monkey kidney epithelial cells exposed to various doses of radiation in vitro and in vivo. Comm.3

    International Nuclear Information System (INIS)

    Machavariani, M.G.

    1979-01-01

    The tetraploidy phenomenon in three and five day cultures of monkey kidney epithelial cells exposed to various doses of X-rays at Gsub(0) stage has been revealed. The data are presented on simple and complex tetraploidal enclo-reduplicated cells in monkey kidney epithelium after whole-body irradiaiton of animals by 60 Co γ-rays in dosage of 620-660 R. The frequency decrease of endoreduplicated cells at the second month coincides with the frequency increase of simple tetraploidal cells. In the investigated culture of monkey kidney epithelial cells, irradiated in vitro, a trend is observed towards the increase of the number of tetraploidal cells. An assumption is made on the possibility of using the frequency of tetraploidal cells ( including lymphocytes) for the purposes of biological dosimetry

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

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    Guanghou Shui

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

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

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    M.F. Ahsan

    2014-06-01

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

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

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

    2015-07-01

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

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

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shahin Zangenehpour

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

  2. Reproductive dysfunction in rhesus monkeys exposed to low levels of polychlorinated biphenyls (Aroclor 1248)

    Energy Technology Data Exchange (ETDEWEB)

    Barsotti, D.A.; Marlar, R.J.; Allen, J.R.

    1976-01-01

    Eighteen female and four male adult Rhesus monkeys were fed the polychlorinated biphenyl (PCB) Aroclor 1248 at levels of either 2.5 or 5.0 ppM in the diet. These levels are equal to, and 50% of, the concentration allowed in certain foods destined for human consumption. After consuming these diets for 2 months, some of the females developed acne, alopecia, erythema and swelling of the eyelids, and by 6 months all females exhibited these changes to some degree. Modifications in serum lipids developed gradually, with a trend towards hypocholesterolaemia, hypolipidaemia and decreased serum triglycerides. In addition there was a shift in the plasma albumin/globulin ratio and an increase in serum glutamic-pyruvic transaminase activity. Analysis of subcutaneous fat showed an accumulation of the PCB isomers in the adipose tissue. The concentrations in this tissue reached a plateau, after which only slight variations were observed. Within 4 months, menstrual cycles were altered: menostaxis and menorrhagia occurred frequently and at times amenorrhoea was apparent. The ability of the animals to maintain pregnancy was impaired, as indicated by frequent resorptions and abortions. When infants were born they were small, and the transplacental movement of PCBs was evident from analyses of skin biopsies of neonates and of autopsy tissue from one stillborn. Moreover, additional accumulation of PCBs occurred in infants during breast feeding. All males fed 5.0 ppM PCB exhibited only slight periorbital oedema and erythema after 14 months on the diet and showed no alterations in their breeding capacities. The data presented indicate that long-term, low-level exposure of female non-human primates to PCBs can affect many important biological parameters.

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

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

    2013-01-01

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

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

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

    2017-06-01

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

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

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

    2017-01-01

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

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

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    Bailey, Jarrod

    2014-11-01

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

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

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    Sarah Papworth

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

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

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

    2008-09-25

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

  9. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in Rhesus monkeys exposed to ozone

    International Nuclear Information System (INIS)

    Castleman, W.L.; Dungworth, D.L.; Schwartz, L.W.; Tyler, W.S.

    1980-01-01

    The pathogenesis of acute respiratory bronchiolitis was examined in Rhesus monkeys exposed to 0.8 ppM ozone for 4 to 50 hours. Epithelial injury and renewal were qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy as well as by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4 to 12 hours of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 hours of exposure, and the highest labeling index (18%) was measured after 50 hours of exposure. Most (67 to 80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20 to 33% were Type 2 epithelial cells. After 50 hours of exposure the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 hours and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. The results indicate that Type 1 epithelial cells lining respiratory bronchioles are the cell types most sensitive to injury and that both cuboidal bronchiolar epithelial cells and Type 2 epithelial cells function as stem cells in epithelial renewal

  10. A Deficit in Face-Voice Integration in Developing Vervet Monkeys Exposed to Ethanol during Gestation

    DEFF Research Database (Denmark)

    Zangenehpour, Shahin; Javadi, Pasha; Ervin, Frank R

    2014-01-01

    . However, a group of normally developing monkeys exhibited a significant preference for the non-matching video. This inability to integrate and thereby discriminate audiovisual stimuli was confined to the integration of faces and voices as revealed by the monkeys' ability to match a dynamic face...... to a complex tone or a black-and-white checkerboard to a pure tone, presumably based on duration and/or onset-offset synchrony. Together, these results suggest that prenatal ethanol exposure negatively affects a specific domain of audiovisual integration. This deficit is confined to the integration...... of information that is presented by the face and the voice and does not affect more elementary aspects of sensory integration....

  11. Kinematics and ontogeny of locomotion in monkeys and human babies.

    Science.gov (United States)

    Niemitz, Carsten

    2002-03-01

    Early ontogenetic stages are often assumed to reflect or to be similar to past phylogenetic stages within the evolution of man. Therefore, as a first step, the quadrupedal crawling locomotion of human children was analysed and compared to the quadrupedal walk of Macaca fascicularis. The movements of the human child were not only more irregular, they differed from the walk of the monkey mainly through extraordinarily short swing phases, and also through strong scoliotic movements of the spine. There is a compulsory synchronisation in the hip and knee joint movements of the human crawling baby. We conclude that human crawling may be a behavioural recapitulation of a quadrupedal evolutionary stage. However, with reference to kinematics, man is not only characterised by his unique, habitually bipedal, upright gait but also by a second, equally unique locomotion, namely crawling, which he assumes for a short phase during his first year of life.--The walking movements of the limbs in toddling infants were mainly characterised by i) rather stiff, abducted arms, which were moved mostly by spine torsions (similar to those of bipedally walking Gorilla) and not as a suspensory pendulum. However, they rather work as levers for the elastic torsion pendulum of the spine. ii) They are also characterised by frequently lacking the minor knee flexion, which occurs at about the heel strike within each stride of the adult human. Besides many other details of the results, foot movements differed from adult ones mainly in that the whole plantar surface was placed flat on the ground within a few milliseconds.

  12. Utility of finger maze test for learning and memory abilities in infants of cynomolgus monkeys exposed to thiamazole.

    Science.gov (United States)

    Inoue, Ayumi; Arima, Akihiro; Kato, Hirohito; Ebihara, Shizufumi

    2014-11-01

    A new type of learning and memory test using a finger maze was conducted in infant cynomolgus monkeys that were exposed to thiamazole (2 and 3.5 mg/kg per day to pregnant animals orally) during the fetal period (gestational days 120 to 150). We modified Tsuchida's original finger maze test method by reducing the number of trials per day and simplifying the criteria for achievement of training, and we added a long-term memory test. In the memory test, thiamazole-exposed infants required greater time to complete the finger maze test than the control infants although no effect was noted in the training or learning test. The results suggest that an impaired long-term memory could be detected by our modified finger maze test. © 2014 Japanese Teratology Society.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

  15. Retosiban Prevents Stretch-Induced Human Myometrial Contractility and Delays Labor in Cynomolgus Monkeys.

    Science.gov (United States)

    Aye, Irving L M H; Moraitis, Alexandros A; Stanislaus, Dinesh; Charnock-Jones, D Stephen; Smith, Gordon C S

    2018-03-01

    Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1) the contractility of human myometrial explants and (2) labor in nonhuman primates. Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys. Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Moreover, stretch-induced stimulation of myometrial contractility was prevented by ERK1/2 inhibitors. Retosiban (10 nM) prevented stretch-induced stimulation of myometrial contractility and phosphorylation of ERK1/2. Moreover, the inhibitory effect of retosiban on stretch-induced ERK1/2 phosphorylation was prevented by coincubation with a 100-fold excess of a peptide OTR antagonist, atosiban. Compared with vehicle-treated cynomolgus monkeys, treatment with oral retosiban (100 to 150 days of gestational age) reduced the risk of spontaneous delivery (hazard ratio = 0.07, 95% confidence interval 0.01 to 0.60, P = 0.015). The OTR acts as a uterine mechanosensor, whereby stretch increases myometrial contractility through agonist-free activation of the OTR. Retosiban prevents this through inverse agonism of the OTR and, in vivo, reduced the likelihood of spontaneous labor in nonhuman primates. We hypothesize that retosiban may be an effective preventative treatment of preterm birth in high-risk multiple pregnancies, an area of unmet clinical need.

  16. Metabolism and disposition of [14C]brivanib alaninate after oral administration to rats, monkeys, and humans.

    Science.gov (United States)

    Gong, Jiachang; Gan, Jinping; Caceres-Cortes, Janet; Christopher, Lisa J; Arora, Vinod; Masson, Eric; Williams, Daphne; Pursley, Janice; Allentoff, Alban; Lago, Michael; Tran, Scott B; Iyer, Ramaswamy A

    2011-05-01

    Brivanib [(R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2,4]triazin-6-yloxy)propan-2-ol, BMS-540215] is a potent and selective dual inhibitor of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling pathways. Its alanine prodrug, brivanib alaninate [(1R,2S)-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester, BMS-582664], is currently under development as an oral agent for the treatment of cancer. This study describes the in vivo biotransformation of brivanib after a single oral dose of [(14)C]brivanib alaninate to intact rats, bile duct-cannulated (BDC) rats, intact monkeys, BDC monkeys, and humans. Fecal excretion was the primary route of elimination of drug-derived radioactivity in animals and humans. In BDC rats and monkeys, the majority of radioactivity was excreted in bile. Brivanib alaninate was rapidly and completely converted via hydrolysis to brivanib in vivo. The area under the curve from zero to infinity of brivanib accounted for 14.2 to 54.3% of circulating radioactivity in plasma in animals and humans, suggesting that metabolites contributed significantly to the total drug-related radioactivity. In plasma from animals and humans, brivanib was a prominent circulating component. All the metabolites that humans were exposed to were also present in toxicological species. On the basis of metabolite exposure and activity against VEGF and FGF receptors of the prominent human circulating metabolites, only brivanib is expected to contribute to the pharmacological effects in humans. Unchanged brivanib was not detected in urine or bile samples, suggesting that metabolic clearance was the primary route of elimination. The primary metabolic pathways were oxidative and conjugative metabolism of brivanib.

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  18. Pharmacokinetic modeling: Prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans

    International Nuclear Information System (INIS)

    Fisher, Jeffrey W.; Twaddle, Nathan C.; Vanlandingham, Michelle; Doerge, Daniel R.

    2011-01-01

    A physiologically based pharmacokinetic (PBPK) model was developed for bisphenol A (BPA) in adult rhesus monkeys using intravenous (iv) and oral bolus doses of 100 μg d6-BPA/kg (). This calibrated PBPK adult monkey model for BPA was then evaluated against published monkey kinetic studies with BPA. Using two versions of the adult monkey model based on monkey BPA kinetic data from and , the aglycone BPA pharmacokinetics were simulated for human oral ingestion of 5 mg d16-BPA per person (Völkel et al., 2002). Völkel et al. were unable to detect the aglycone BPA in plasma, but were able to detect BPA metabolites. These human model predictions of the aglycone BPA in plasma were then compared to previously published PBPK model predictions obtained by simulating the Völkel et al. kinetic study. Our BPA human model, using two parameter sets reflecting two adult monkey studies, both predicted lower aglycone levels in human serum than the previous human BPA PBPK model predictions. BPA was metabolized at all ages of monkey (PND 5 to adult) by the gut wall and liver. However, the hepatic metabolism of BPA and systemic clearance of its phase II metabolites appear to be slower in younger monkeys than adults. The use of the current non-human primate BPA model parameters provides more confidence in predicting the aglycone BPA in serum levels in humans after oral ingestion of BPA. -- Highlights: ► A bisphenol A (BPA) PBPK model for the infant and adult monkey was constructed. ► The hepatic metabolic rate of BPA increased with age of the monkey. ► The systemic clearance rate of metabolites increased with age of the monkey. ► Gut wall metabolism of orally administered BPA was substantial across all ages of monkeys. ► Aglycone BPA plasma concentrations were predicted in humans orally given oral doses of deuterated BPA.

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

    Science.gov (United States)

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

    2003-06-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  1. Comparison of predictability for human pharmacokinetics parameters among monkeys, rats, and chimeric mice with humanised liver.

    Science.gov (United States)

    Miyamoto, Maki; Iwasaki, Shinji; Chisaki, Ikumi; Nakagawa, Sayaka; Amano, Nobuyuki; Hirabayashi, Hideki

    2017-12-01

    1. The aim of the present study was to evaluate the usefulness of chimeric mice with humanised liver (PXB mice) for the prediction of clearance (CL t ) and volume of distribution at steady state (Vd ss ), in comparison with monkeys, which have been reported as a reliable model for human pharmacokinetics (PK) prediction, and with rats, as a conventional PK model. 2. CL t and Vd ss values in PXB mice, monkeys and rats were determined following intravenous administration of 30 compounds known to be mainly eliminated in humans via the hepatic metabolism by various drug-metabolising enzymes. Using single-species allometric scaling, human CL t and Vd ss values were predicted from the three animal models. 3. Predicted CL t values from PXB mice exhibited the highest predictability: 25 for PXB mice, 21 for monkeys and 14 for rats were predicted within a three-fold range of actual values among 30 compounds. For predicted human Vd ss values, the number of compounds falling within a three-fold range was 23 for PXB mice, 24 for monkeys, and 16 for rats among 29 compounds. PXB mice indicated a higher predictability for CL t and Vd ss values than the other animal models. 4. These results demonstrate the utility of PXB mice in predicting human PK parameters.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  4. Canine distemper virus isolated from a monkey efficiently replicates on Vero cells expressing non-human primate SLAM receptors but not human SLAM receptor.

    Science.gov (United States)

    Feng, Na; Liu, Yuxiu; Wang, Jianzhong; Xu, Weiwei; Li, Tiansong; Wang, Tiecheng; Wang, Lei; Yu, Yicong; Wang, Hualei; Zhao, Yongkun; Yang, Songtao; Gao, Yuwei; Hu, Guixue; Xia, Xianzhu

    2016-08-02

    In 2008, an outbreak of canine distemper virus (CDV) infection in monkeys was reported in China. We isolated CDV strain (subsequently named Monkey-BJ01-DV) from lung tissue obtained from a rhesus monkey that died in this outbreak. We evaluated the ability of this virus on Vero cells expressing SLAM receptors from dog, monkey and human origin, and analyzed the H gene of Monkey-BJ01-DV with other strains. The Monkey-BJ01-DV isolate replicated to the highest titer on Vero cells expressing dog-origin SLAM (10(5.2±0.2) TCID50/ml) and monkey-origin SLAM (10(5.4±0.1) TCID50/ml), but achieved markedly lower titers on human-origin SLAM cells (10(3.3±0.3) TCID50/ml). Phylogenetic analysis of the full-length H gene showed that Monkey-BJ01-DV was highly related to other CDV strains obtained during recent CDV epidemics among species of the Canidae family in China, and these Monkey strains CDV (Monkey-BJ01-DV, CYN07-dV, Monkey-KM-01) possessed a number of amino acid specific substitutions (E276V, Q392R, D435Y and I542F) compared to the H protein of CDV epidemic in other animals at the same period. Our results suggested that the monkey origin-CDV-H protein could possess specific substitutions to adapt to the new host. Monkey-BJ01-DV can efficiently use monkey- and dog-origin SLAM to infect and replicate in host cells, but further adaptation may be required for efficient replication in host cells expressing the human SLAM receptor.

  5. Finger pressure adjustments to various object configurations during precision grip in humans and monkeys.

    Science.gov (United States)

    Viaro, Riccardo; Tia, Banty; Coudé, Gino; Canto, Rosario; Oliynyk, Andriy; Salmas, Paola; Masia, Lorenzo; Sandini, Giulio; Fadiga, Luciano

    2017-06-01

    In this study, we recorded the pressure exerted onto an object by the index finger and the thumb of the preferred hand of 18 human subjects and either hand of two macaque monkeys during a precision grasping task. The to-be-grasped object was a custom-made device composed by two plates which could be variably oriented by a motorized system while keeping constant the size and thus grip dimension. The to-be-grasped plates were covered by an array of capacitive sensors to measure specific features of finger adaptation, namely pressure intensity and centroid location and displacement. Kinematic measurements demonstrated that for human subjects and for monkeys, different plate configurations did not affect wrist velocity and grip aperture during the reaching phase. Consistently, at the instant of fingers-plates contact, pressure centroids were clustered around the same point for all handle configurations. However, small pressure centroid displacements were specifically adopted for each configuration, indicating that both humans and monkeys can display finger adaptation during precision grip. Moreover, humans applied stronger thumb pressure intensity, performed less centroid displacement and required reduced adjustment time, as compared to monkeys. These pressure patterns remain similar when different load forces were required to pull the handle, as ascertained by additional measurements in humans. The present findings indicate that, although humans and monkeys share common features in motor control of grasping, they differ in the adjustment of fingertip pressure, probably because of skill and/or morphology divergences. Such a precision grip device may form the groundwork for future studies on prehension mechanisms. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. The effects of inhaled corticosteroids on intrinsic responsiveness and histology of airways from infant monkeys exposed to house dust mite allergen and ozone

    International Nuclear Information System (INIS)

    Joad, Jesse P.; Kott, Kayleen S.; Bric, John M.; Schelegle, Edward S.; Gershwin, Laurel J.; Plopper, Charles G.; Peake, Janice L.; Pinkerton, Kent E.

    2008-01-01

    Inhaled corticosteroids (ICS) are recommended to treat infants with asthma, some with intermittent asthma. We previously showed that exposing infant monkeys to allergen/ozone resulted in asthma-like characteristics of their airways. We evaluated the effects of ICS on histology and intrinsic responsiveness of allergen/ozone-exposed and normal infant primate airways. Infant monkeys were exposed by inhalation to (1) filtered air and saline, (2) house dust mite allergen (HDMA) + ozone and saline, (3) filtered air and ICS (budesonide) or (4) HDMA + ozone and ICS. Allergen/ozone exposures started at 1 month and ICS at 3 months of age. At 6 months of age, methacholine-induced changes in luminal area of airways in proximal and distal lung slices were determined using videomicrometry, followed by histology of the same slices. Proximal airway responsiveness was increased by allergen/ozone and by ICS. Eosinophil profiles were increased by allergen/ozone in both proximal and distal airways, an effect that was decreased by ICS in distal airways. In both allergen/ozone- and air-exposed monkeys, ICS increased the number of alveolar attachments in distal airways, decreased mucin in proximal airways and decreased epithelial volume in both airways. ICS increased smooth muscle in air-exposed animals while decreasing it in allergen/ozone-exposed animals in both airways. In proximal airways, there was a small but significant positive correlation between smooth muscle and airway responsiveness, as well as between alveolar attachments and responsiveness. ICS change morphology and function in normal airways as well as allergen/ozone-exposed airways, suggesting that they should be reserved for infants with active symptoms

  7. Comparative anatomy of the prosubiculum, subiculum, presubiculum, postsubiculum, and parasubiculum in human, monkey, and rodent.

    Science.gov (United States)

    Ding, Song-Lin

    2013-12-15

    The subicular complex, including the prosubiculum (ProS), subiculum (Sub), presubiculum, postsubiculum (PoS), and parasubiculum (PaS), plays important roles in the medial temporal memory system and is heavily involved in many neurological diseases such as Alzheimer's disease and epilepsy. In the literature, the ProS (in primate) and PoS (in rodent) are inconstantly identified, making data comparison difficult across species. This review is an attempt to discuss equivalencies and extent of the five subicular components in human, monkey, and rodent based on available information on their cytoarchitecture, chemoarchitecture, molecular signature, and neural connectivity. All five subicular cortices exist in human, monkey, and rodent. In human and monkey, the ProS and Sub extend into the uncal region anteriorly, and the PoS and PaS reach the cingulate isthmus posteriorly. In rodent, most of the typical subicular cortices are located in the dorsal and caudal portions of the hippocampal formation, and the modified version of the ventral ProS and Sub corresponds to the modified description of the uncal ProS and Sub in monkey and human. An interesting triangular region in rodent located at the juncture of the PoS, PaS, retrosplenial cortex, and visual cortex appears to be the equivalent of the monkey area prostriata. Major connections of the five subicular cortices are also summarized based on unified criteria discussed in this review, with distinct connections revealed between the ProS and the Sub. Copyright © 2013 Wiley Periodicals, Inc.

  8. Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen.

    Science.gov (United States)

    Larson, Shawnessy D; Schelegle, Edward S; Walby, William F; Gershwin, Laural J; Fanuccihi, Michelle V; Evans, Michael J; Joad, Jesse P; Tarkington, Brian K; Hyde, Dallas M; Plopper, Charles G

    2004-02-01

    Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O(3)) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O(3), or HDMA + O(3) for 11 episodes (5 days each, 0.5 ppm O(3), 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P < 0.05) decrements in the density of epithelial nerves in monkeys exposed to HDMA or O(3), while in monkeys exposed to HDMA + O(3) there was a greater significant (P < 0.05) reduction in epithelial innervation. In animals exposed to O(3) or HDMA + O(3) there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium.

  9. Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

    Science.gov (United States)

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

    2012-01-01

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

  10. Space representation for eye movements is more contralateral in monkeys than in humans

    OpenAIRE

    Kagan, Igor; Iyer, Asha; Lindner, Axel; Andersen, Richard A.

    2010-01-01

    Contralateral hemispheric representation of sensory inputs (the right visual hemifield in the left hemisphere and vice versa) is a fundamental feature of primate sensorimotor organization, in particular the visuomotor system. However, many higher-order cognitive functions in humans show an asymmetric hemispheric lateralization—e.g., right brain specialization for spatial processing—necessitating a convergence of information from both hemifields. Electrophysiological studies in monkeys and fun...

  11. The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance

    DEFF Research Database (Denmark)

    Innocenti, Giorgio M.; Dyrby, Tim Bjørn; Andersen, Kasper Winther

    2017-01-01

    The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species......, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4–0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon...... diameters and conduction distance are monkey and, by extrapolation,

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

    Science.gov (United States)

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

    2011-01-01

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

  13. Metabolite analysis of [11C]Ro15-4513 in mice, rats, monkeys and humans

    International Nuclear Information System (INIS)

    Kida, T.; Noguchi, J.; Zhang, M.-R.; Suhara, T.; Suzuki, K.

    2003-01-01

    We performed in vitro and in vivo assays of the metabolism of [ 11 C]Ro15-4513 over time in the plasma of mice, rats, monkeys and humans, using a radio-HPLC equipped with a sensitive positron detector, in order to compare the metabolic rates of the radiopharmaceutical agent among the different animal species and to establish a highly sensitive analytical method for the radiotracer agent. We also examined the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats. The analytical method used in this study permitted detection of even extremely low levels of radioactivity (approximately 5,000 dpm). In vitro experiments revealed that [ 11 C]Ro15-4513 in the blood was metabolized to hydrolysate [ 11 C]A. The species were classified in descending order of the metabolic rate of the radiotracer in vitro as follows; mice, rats, and monkeys/humans. In the in vitro experiment, the percentage of the unchanged drug in the plasma at 60 minutes postdose was 9% in mice, 70% in rats, 97% in monkeys, and 98% in humans. In vivo metabolite analysis in the blood showed the presence of two radioactive metabolites, consisting of one hydrolysate [ 11 C]A and another unidentified substance. The species were classified in descending order of the metabolic rate of the radiotracer in vivo as follows; mice, rats/humans, and monkeys. The percentage of the unchanged drug in the plasma was 6% in mice, 21% in rats, 26% in humans, and 40% in monkeys. Furthermore, the in vitro and in vivo experiments conducted to analyze the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats revealed that the radiotracer was metabolized to some extent in the brain tissue of these animals. In the in vivo experiment, the percentage of the unchanged drug at 60 min postdose was 86% in the brain tissue of mice and 88% in the brain tissue of rats, while in the in vitro experiment, the corresponding percentage was 93% in mice, and 91% in rats

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

    Science.gov (United States)

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

    2018-01-02

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

  15. CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.

    Science.gov (United States)

    Kang, Yu; Zheng, Bo; Shen, Bin; Chen, Yongchang; Wang, Lei; Wang, Jianying; Niu, Yuyu; Cui, Yiqiang; Zhou, Jiankui; Wang, Hong; Guo, Xuejiang; Hu, Bian; Zhou, Qi; Sha, Jiahao; Ji, Weizhi; Huang, Xingxu

    2015-12-20

    Mutations in the DAX1 locus cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH), which manifest with primary adrenal insufficiency and incomplete or absent sexual maturation, respectively. The associated defects in spermatogenesis can range from spermatogenic arrest to Sertoli cell only syndrome. Conclusions from Dax1 knockout mouse models provide only limited insight into AHC/HH disease mechanisms, because mouse models exhibit more extensive abnormalities in testicular development, including disorganized and incompletely formed testis cords with decreased number of peritubular myoid cells and male-to-female sex reversal. We previously reported successful clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome targeting in cynomolgus monkeys. Here, we describe a male fetal monkey in which targeted genome editing using CRISPR/Cas9 produced Dax1-null mutations in most somatic tissues and in the gonads. This DAX1-deficient monkey displayed defects in adrenal gland development and abnormal testis architecture with small cords, expanded blood vessels and extensive fibrosis. Sertoli cell formation was not affected. This phenotype strongly resembles findings in human patients with AHC-HH caused by mutations in DAX1. We further detected upregulation of Wnt/β-catenin-VEGF signaling in the fetal Dax1-deficient testis, suggesting abnormal activation of signaling pathways in the absence of DAX1 as one mechanism of AHC-HH. Our study reveals novel insight into the role of DAX1 in HH and provides proof-of-principle for the generation of monkey models of human disease via CRISPR/Cas9-mediated gene targeting. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2009-08-01

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

  17. Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human.

    Science.gov (United States)

    Li, Yan; Zhou, Yanyan; Si, Nan; Han, Lingyu; Ren, Wei; Xin, Shaokun; Wang, Hongjie; Zuo, Ran; Wei, Xiaolu; Yang, Jian; Zhao, Haiyu; Bian, Baolin

    2017-11-01

    Protoberberine alkaloids including berberine, palmatine, jatrorrhizine, coptisine, and epiberberine are major components in many medicinal plants. They have been widely used for the treatment of cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. However, the metabolism of five protoberberine alkaloids among different species has not been clarified previously. In order to elaborate on the in vitro metabolism of them, a comparative analysis of their metabolic profile in rat, rhesus monkey, and human liver microsomes was carried out using ultrahigh-performance liquid chromatography coupled with a high-resolution linear trap quadrupole-Orbitrap mass spectrometer (UHPLC-electrospray ionization-Orbitrap MS) for the first time. Each metabolite was identified and semiquantified by its accurate mass data and peak area. Fifteen metabolites were characterized based on accurate MS/MS spectra and the proposed MS/MS fragmentation pathways including demethylation, hydroxylation, and methyl reduction. Among them, the content of berberine metabolites in human liver microsomes was similar with those in rhesus monkey liver microsomes, whereas berberine in rat liver microsomes showed no demethylation metabolites and the content of metabolites showed significant differences with that in human liver microsomes. On the contrary, the metabolism of palmatine in rat liver microsomes resembled that in human liver microsomes. The content of jatrorrhizine metabolites presented obvious differences in all species. The HR-ESI-MS/MS fragmentation behavior of protoberberine alkaloids and their metabolic profile in rat, rhesus monkey, and human liver microsomes were investigated for the first time. The results demonstrated that the biotransformation characteristics of protoberberine alkaloids among different species had similarities as well differences that would be beneficial for us to better understand the pharmacological activities of protoberberine alkaloids

  18. Monkey Lipsmacking Develops Like the Human Speech Rhythm

    Science.gov (United States)

    Morrill, Ryan J.; Paukner, Annika; Ferrari, Pier F.; Ghazanfar, Asif A.

    2012-01-01

    Across all languages studied to date, audiovisual speech exhibits a consistent rhythmic structure. This rhythm is critical to speech perception. Some have suggested that the speech rhythm evolved "de novo" in humans. An alternative account--the one we explored here--is that the rhythm of speech evolved through the modification of rhythmic facial…

  19. Intraocular distribution of melanin in human, monkey, rabbit, minipig and dog eyes.

    Science.gov (United States)

    Durairaj, Chandrasekar; Chastain, James E; Kompella, Uday B

    2012-05-01

    The purpose of this study was to quantify the melanin pigment content in sclera, choroid-RPE, and retina, three tissues encountered during transscleral drug delivery to the vitreous, in human, rabbit, monkey, minipig, and dog models. Strain differences were assessed in NZW × NZR F1 and Dutch belted rabbits and Yucatan and Gottingen minipigs. The choroid-RPE and retina tissues were divided into central (posterior pole area) and peripheral (away from posterior pole) regions while the sclera was analyzed without such division. Melanin content in the tissues was analyzed using a colorimetric assay. In all species the rank order for pigment content was: choroid-RPE >retina ≥ sclera, except in humans, where scleral melanin levels were higher than retina and central choroid. The melanin content in a given tissue differed between species. Further, while the peripheral tissue pigment levels tended to be generally higher compared to the central regions, these differences were significant in human in the case of choroid-RPE and in human, monkey, and dogs in the case of retina. Strain difference was observed only in the central choroid-RPE region of rabbits (NZW × NZR F1 >Dutch Belted). Species, strain, and regional differences exist in the melanin pigment content in the tissues of the posterior segment of the eye, with Gottingen minipig being closest to humans among the animals assessed. These differences in melanin content might contribute to differences in drug binding, delivery, and toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Metabolism of ginger component [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human.

    Science.gov (United States)

    Chen, Huadong; Soroka, Dominique; Zhu, Yingdong; Sang, Shengmin

    2013-05-01

    There are limited data on the metabolism of [6]-shogaol (6S), a major bioactive component of ginger. This study demonstrates metabolism of 6S in liver microsomes from mouse, rat, dog, monkey, and human. The in vitro metabolism of 6S was compared among five species using liver microsomes from mouse, rat, dog, monkey, and human. Following incubations with 6S, three major reductive metabolites 1-(4'-hydroxy-3'-methoxyphenyl)-4-decen-3-ol (M6), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9), and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11), as well as two new oxidative metabolites (1E,4E)-1-(4'-hydroxy-3'-methoxyphenyl)-deca-1,4-dien-3-one (M14) and (E)-1-(4'-hydroxy-3'-methoxyphenyl)-dec-1-en-3-one (M15) were found in all species. The kinetic parameters of M6 in liver microsomes from each respective species were quantified using Michaelis-Menten theory. A broad CYP-450 inhibitor, 1-aminobenzotriazole, precluded the formation of oxidative metabolites, M14 and M15, and 18β-glycyrrhetinic acid, an aldo-keto reductase inhibitor, eradicated the formation of the reductive metabolites M6, M9, and M11 in all species. Metabolites M14 and M15 were tested for cancer cell growth inhibition and induction of apoptosis and both showed substantial activity, with M14 displaying greater potency than 6S. We conclude that 6S is metabolized extensively in mammalian species mouse, rat, dog, monkey, and human, and that there are significant interspecies differences to consider when planning preclinical trials toward 6S chemoprevention. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2018-05-02

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

  2. Mapping visual cortex in monkeys and humans using surface-based atlases

    Science.gov (United States)

    Van Essen, D. C.; Lewis, J. W.; Drury, H. A.; Hadjikhani, N.; Tootell, R. B.; Bakircioglu, M.; Miller, M. I.

    2001-01-01

    We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

  3. High-frequency oscillations in human and monkey neocortex during the wake-sleep cycle.

    Science.gov (United States)

    Le Van Quyen, Michel; Muller, Lyle E; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G; Dehghani, Nima; Destexhe, Alain

    2016-08-16

    Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake-sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS.

  4. High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle

    Science.gov (United States)

    Le Van Quyen, Michel; Muller, Lyle E.; Telenczuk, Bartosz; Halgren, Eric; Cash, Sydney; Hatsopoulos, Nicholas G.; Dehghani, Nima; Destexhe, Alain

    2016-01-01

    Beta (β)- and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake–sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β- and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β- and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β- and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS. PMID:27482084

  5. Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen

    International Nuclear Information System (INIS)

    Larson, Shawnessy D.; Schelegle, Edward S.; Walby, William F.; Gershwin, Laural J.; Fanuccihi, Michelle V.; Evans, Michael J.; Joad, Jesse P.; Tarkington, Brian K.; Hyde, Dallas M.; Plopper, Charles G.

    2004-01-01

    Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O 3 ) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O 3 , or HDMA + O 3 for 11 episodes (5 days each, 0.5 ppm O 3 , 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P 3 , while in monkeys exposed to HDMA + O 3 there was a greater significant (P 3 or HDMA + O 3 there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium

  6. Comparison of minipig, dog, monkey and human drug metabolism and disposition.

    Science.gov (United States)

    Dalgaard, Lars

    2015-01-01

    This article gives an overview of the drug metabolism and disposition (ADME) characteristics of the most common non-rodent species used in toxicity testing of drugs (minipigs, dogs, and monkeys) and compares these to human characteristics with regard to enzymes mediating the metabolism of drugs and the transport proteins which contribute to the absorption, distribution and excretion of drugs. Literature on ADME and regulatory guidelines of relevance in drug development of small molecules has been gathered. Non-human primates (monkeys) are the species that is closest to humans in terms of genetic homology. Dogs have an advantage due to the ready availability of comprehensive background data for toxicological safety assessment and dogs are easy to handle. Pigs have been used less than dogs and monkeys as a model in safety assessment of drug candidates. However, when a drug candidate is metabolised by aldehyde oxidase (AOX1), N-acetyltransferases (NAT1 and NAT2) or cytochrome (CYP2C9-like) enzymes which are not expressed in dogs, but are present in pigs, this species may be a better choice than dogs, provided that adequate exposure can be obtained in pigs. Conversely, pigs might not be the right choice if sulfation, involving 3-phospho-adenosyl-5-phosphosulphate sulphotransferase (PAPS) is an important pathway in the human metabolism of a drug candidate. In general, the species selection should be based on comparison between in vitro studies with human cell-based systems and animal-cell-based systems. Results from pharmacokinetic studies are also important for decision-making by establishing the obtainable exposure level in the species. Access to genetically humanized mouse models and highly sensitive analytical methods (accelerator mass spectrometry) makes it possible to improve the chance of finding all metabolites relevant for humans before clinical trials have been initiated and, if necessary, to include another animal species before long term toxicity studies are

  7. (Ir)rational choices of humans, rhesus macaques, and capuchin monkeys in dynamic stochastic environments.

    Science.gov (United States)

    Watzek, Julia; Brosnan, Sarah F

    2018-05-28

    Human and animal decision-making is known to violate rational expectations in a variety of contexts. Previous models suggest that statistical structures of real-world environments can favor such seemingly irrational behavior, but this has not been tested empirically. We tested 16 capuchin monkeys, seven rhesus monkeys, and 30 humans in a computerized experiment that implemented such stochastic environments. Subjects chose from among up to three options of different value that disappeared and became available again with different probabilities. All species overwhelmingly chose transitively (A > B > C) in the control condition, where doing so maximized overall gain. Most subjects also adhered to transitivity in the test condition, where it was suboptimal, but ultimately led to negligible losses compared to the optimal, non-transitive strategy. We used a modelling approach to show that differences in temporal discounting may account for this pattern of choices on a proximate level. Specifically, when short- and long-term goals are valued similarly, near-optimal decision rules can map onto rational choice principles. Such cognitive shortcuts have been argued to have evolved to preserve mental resources without sacrificing good decision-making, and here we provide evidence that these heuristics can provide almost identical outcomes even in situations in which they lead to suboptimal choices. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Monkeys and humans take local uncertainty into account when localizing a change.

    Science.gov (United States)

    Devkar, Deepna; Wright, Anthony A; Ma, Wei Ji

    2017-09-01

    Since sensory measurements are noisy, an observer is rarely certain about the identity of a stimulus. In visual perception tasks, observers generally take their uncertainty about a stimulus into account when doing so helps task performance. Whether the same holds in visual working memory tasks is largely unknown. Ten human and two monkey subjects localized a single change in orientation between a sample display containing three ellipses and a test display containing two ellipses. To manipulate uncertainty, we varied the reliability of orientation information by making each ellipse more or less elongated (two levels); reliability was independent across the stimuli. In both species, a variable-precision encoding model equipped with an "uncertainty-indifferent" decision rule, which uses only the noisy memories, fitted the data poorly. In both species, a much better fit was provided by a model in which the observer also takes the levels of reliability-driven uncertainty associated with the memories into account. In particular, a measured change in a low-reliability stimulus was given lower weight than the same change in a high-reliability stimulus. We did not find strong evidence that observers took reliability-independent variations in uncertainty into account. Our results illustrate the importance of studying the decision stage in comparison tasks and provide further evidence for evolutionary continuity of working memory systems between monkeys and humans.

  9. Disruption of a hydrogen bond network in human versus spider monkey cytochrome c affects heme crevice stability.

    Science.gov (United States)

    Goldes, Matthew E; Jeakins-Cooley, Margaret E; McClelland, Levi J; Mou, Tung-Chung; Bowler, Bruce E

    2016-05-01

    The hypothesis that the recent rapid evolution of primate cytochromes c, which primarily involves residues in the least stable Ω-loop (Ω-loop C, residues 40-57), stabilizes the heme crevice of cytochrome c relative to other mammals, is tested. To accomplish this goal, we have compared the properties of human and spider monkey cytochrome c and a set of four variants produced in the process of converting human cytochrome c into spider monkey cytochrome c. The global stability of all variants has been measured by guanidine hydrochloride denaturation. The stability of the heme crevice has been assessed with the alkaline conformational transition. Structural insight into the effects of the five amino acid substitutions needed to convert human cytochrome c into spider monkey cytochrome c is provided by a 1.15Å resolution structure of spider monkey cytochrome c. The global stability for all variants is near 9.0kcal/mol at 25°C and pH7, which is higher than that observed for other mammalian cytochromes c. The heme crevice stability is more sensitive to the substitutions required to produce spider monkey cytochrome c with decreases of up to 0.5 units in the apparent pKa of the alkaline conformational transition relative to human cytochrome c. The structure of spider monkey cytochrome c indicates that the Y46F substitution destabilizes the heme crevice by disrupting an extensive hydrogen bond network that connects three surface loops including Ω-loop D (residues 70-85), which contains the Met80 heme ligand. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    1984-02-15

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

  11. Responses to the Assurance game in monkeys, apes, and humans using equivalent procedures

    DEFF Research Database (Denmark)

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

    2011-01-01

    There is great interest in the evolution of economic behavior. In typical studies, species are asked to play one of a series of economic games, derived from game theory, and their responses are compared. The advantage of this approach is the relative level of consistency and control that emerges...... from the games themselves; however, in the typical experiment, procedures and conditions differ widely, particularly between humans and other species. Thus, in the current study, we investigated how three primate species, capuchin monkeys, chimpanzees, and humans, played the Assurance (or Stag Hunt......) game using procedures that were, to the best of our ability, the same across species, particularly with respect to training and pretesting. Our goal was to determine what, if any, differences existed in the ways in which these species made decisions in this game. We hypothesized differences along...

  12. Nonverbal working memory of humans and monkeys: rehearsal in the sketchpad?

    Science.gov (United States)

    Washburn, D. A.; Astur, R. S.; Rumbaugh, D. M. (Principal Investigator)

    1998-01-01

    Investigations of working memory tend to focus on the retention of verbal information. The present experiments were designed to characterize the active maintenance rehearsal process used in the retention of visuospatial information. Rhesus monkeys (Macaca mulatta; N = 6) were tested as well as humans (total N = 90) because these nonhuman primates have excellent visual working memory but, unlike humans, cannot verbally recode the stimuli to employ verbal rehearsal mechanisms. A series of experiments was conducted using a distractor-task paradigm, a directed forgetting procedure, and a dual-task paradigm. No evidence was found for an active maintenance process for either species. Rather, it appears that information is maintained in the visuospatial sketchpad without active rehearsal.

  13. Morphology and accommodative function of the vitreous zonule in human and monkey eyes.

    Science.gov (United States)

    Lütjen-Drecoll, Elke; Kaufman, Paul L; Wasielewski, Rainer; Ting-Li, Lin; Croft, Mary Ann

    2010-03-01

    To explore the attachments of the posterior zonule and vitreous in relation to accommodation and presbyopia in monkeys and humans. Novel scanning electron microscopy (SEM) and ultrasound biomicroscopy (UBM) techniques were used to visualize the anterior, intermediate, and posterior vitreous zonule and their connections to the ciliary body, vitreous membrane, lens capsule, and ora serrata, and to characterize their age-related changes and correlate them with loss of accommodative forward movement of the ciliary body. alpha-Chymotrypsin was used focally to lyse the vitreous zonule and determine the effect on movement of the accommodative apparatus in monkeys. The vitreous attached to the peripheral lens capsule and the ora serrata directly. The pars plana zonule and the posterior tines of the anterior zonule were separated from the vitreous membrane except for strategically placed attachments, collectively termed the vitreous zonule, that may modulate and smooth the forward and backward movements of the entire system. Age-dependent changes in these relationships correlated significantly with loss of accommodative amplitude. Lysis of the intermediate vitreous zonule partially restored accommodative movement. The vitreous zonule system may help to smoothly translate to the lens the driving forces of accommodation and disaccommodation generated by the ciliary muscle, while maintaining visual focus and protecting the lens capsule and ora serrata from acute tractional forces. Stiffening of the vitreous zonular system may contribute to age-related loss of accommodation and offer a therapeutic target for presbyopia.

  14. The binding patterns of antisera to sex steroids and human gonadotropins on human and rhesus monkey spermatozoa.

    Science.gov (United States)

    Allag, I S; Das, R P; Roy, S

    1983-01-01

    The presence of different hormones on the surface of ejaculated spermatozoa was determined by immunofluorescence studies of the binding patterns of specific antisera to these hormones. There were striking similarities in the binding pattern of antisera to steroid hormones found on human and monkey spermatozoa. Assuming the intensity of fluorescence is proportional to the concentration of the hormone, concentrations of testosterone on the acrosomal and the postacrosomal regions were higher than levels of progesterone and estrogens. Spermatozoa with a "tapering head" had more hCG bound on the acrosomal and postacrosomal regions than spermatozoa with "normal head" (oval shaped). Correlating these findings to the functions of spermatozoa will require further studies.

  15. METABOLISM AND DNA ADDUCT FORMATION OF 2-ACETYLAMINOFLUORENE BY BLADDER EXPLANTS FROM HUMAN, DOG, MONKEY, HAMSTER AND RAT

    Science.gov (United States)

    It is concluded that bladder explants of the human, dog, monkey, hamster, and rat metabolize AAF mainly to ring-hydroxylated products, but also form small amounts of the proximate carcinogenic metabolite N-hydroxy-AAF. Neither the overall binding of AAF to bladder DNA, nor the fo...

  16. The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells

    International Nuclear Information System (INIS)

    O'Neill, Frank J.; Greenlee, John E.; Carney, Helen

    2003-01-01

    Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

  17. Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency

    Science.gov (United States)

    Saul, Louise; Saul, Louise; Josephs, Debra H; Josephs, Debra H; Cutler, Keith; Cutler, Keith; Bradwell, Andrew; Bradwell, Andrew; Karagiannis, Panagiotis; Karagiannis, Panagiotis; Selkirk, Chris; Selkirk, Chris; Gould, Hannah J; Gould, Hannah J; Jones, Paul; Jones, Paul; Spicer, James F; Spicer, James F; Karagiannis, Sophia N; Karagiannis, Sophia N

    2014-01-01

    Background: Due to genetic similarities with humans, primates of the macaque genus such as the cynomolgus monkey are often chosen as models for toxicology studies of antibody therapies. IgE therapeutics in development depend upon engagement with the FcεRI and FcεRII receptors on immune effector cells for their function. Only limited knowledge of the primate IgE immune system is available to inform the choice of models for mechanistic and safety evaluations.   Methods: The recognition of human IgE by peripheral blood lymphocytes from cynomolgus monkey and man was compared. We used effector cells from each species in ex vivo affinity, dose-response, antibody-receptor dissociation and potency assays. Results: We report cross-reactivity of human IgE Fc with cynomolgus monkey cells, and comparable binding kinetics to peripheral blood lymphocytes from both species. In competition and dissociation assays, however, human IgE dissociated faster from cynomolgus monkey compared with human effector cells. Differences in association and dissociation kinetics were reflected in effector cell potency assays of IgE-mediated target cell killing, with higher concentrations of human IgE needed to elicit effector response in the cynomolgus monkey system. Additionally, human IgE binding on immune effector cells yielded significantly different cytokine release profiles in each species. Conclusion: These data suggest that human IgE binds with different characteristics to human and cynomolgus monkey IgE effector cells. This is likely to affect the potency of IgE effector functions in these two species, and so has relevance for the selection of biologically-relevant model systems when designing pre-clinical toxicology and functional studies. PMID:24492303

  18. Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

    Science.gov (United States)

    Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

    2011-01-01

    Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

  19. Genetic polymorphisms of drug-metabolizing cytochrome P450 enzymes in cynomolgus and rhesus monkeys and common marmosets in preclinical studies for humans.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

    2017-12-23

    Cynomolgus monkeys (Macaca fascicularis, Old World Monkeys) and common marmosets (Callithrix jacchus, New World Monkeys) have been widely, and expectedly, used as non-human primate models in drug development studies. Major drug-metabolizing cytochrome P450 (P450) enzymes information is now available that supports these primate species as animal models, and it is established that multiple forms of cynomolgus monkey and common marmoset P450 enzymes have generally similar substrate recognition functionality to human P450 enzymes. This research update provides information on genetic polymorphisms of P450 enzymes in cynomolgus monkey and common marmoset like human P450 enzymes. Information on rhesus monkeys (Macaca mulatta), another macaque species used in drug metabolism studies, is also included for comparison. Among a variety of cynomolgus monkey P450 variants investigated, typical examples include individual pharmacokinetic data for efavirenz and R-warfarin associated with cynomolgus monkey P450 2C9 (formerly 2C43) and 2C19 (2C75) variants, respectively, and for R-omeprazole and S-warfarin associated with marmoset P450 2C19 variants. These findings provide a foundation for understanding the individual pharmacokinetic and toxicological results in non-human primates as preclinical models and will help to further support understanding of molecular mechanisms of human P450 function. In addition to these polymorphic P450 enzymes, effects of aging on some drug clearances mediated by cynomolgus monkey and common marmoset P450 enzymes were found in elder animals or animals pretreated with rifampicin. This review describes genetic and acquired individual differences in cynomolgus monkey and common marmoset P450 enzymes involved in drug oxidation associated with pharmacological and/or toxicological effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-12-01

    Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Directory of Open Access Journals (Sweden)

    John K Thuita

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-09-15

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

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

    Science.gov (United States)

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

    2015-09-01

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

  4. Cholinergic Modulation of Cortical Microcircuits Is Layer-Specific: Evidence from Rodent, Monkey and Human Brain

    Directory of Open Access Journals (Sweden)

    Joshua Obermayer

    2017-12-01

    Full Text Available Acetylcholine (ACh signaling shapes neuronal circuit development and underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. During behavior, activation of muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs by ACh alters the activation state of neurons, and neuronal circuits most likely process information differently with elevated levels of ACh. In several brain regions, ACh has been shown to alter synaptic strength as well. By changing the rules for synaptic plasticity, ACh can have prolonged effects on and rearrange connectivity between neurons that outlasts its presence. From recent discoveries in the mouse, rat, monkey and human brain, a picture emerges in which the basal forebrain (BF cholinergic system targets the neocortex with much more spatial and temporal detail than previously considered. Fast cholinergic synapses acting on a millisecond time scale are abundant in the mammalian cerebral cortex, and provide BF cholinergic neurons with the possibility to rapidly alter information flow in cortical microcircuits. Finally, recent studies have outlined novel mechanisms of how cholinergic projections from the BF affect synaptic strength in several brain areas of the rodent brain, with behavioral consequences. This review highlights these exciting developments and discusses how these findings translate to human brain circuitries.

  5. Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice

    Science.gov (United States)

    Sherman, Maxwell A.; Lee, Shane; Law, Robert; Haegens, Saskia; Thorn, Catherine A.; Hämäläinen, Matti S.; Moore, Christopher I.; Jones, Stephanie R.

    2016-01-01

    Human neocortical 15–29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function. PMID:27469163

  6. Comparative metabolism of honokiol in mouse, rat, dog, monkey, and human hepatocytes.

    Science.gov (United States)

    Jeong, Hyeon-Uk; Kim, Ju-Hyun; Kong, Tae Yeon; Choi, Won Gu; Lee, Hye Suk

    2016-04-01

    Honokiol has antitumor, antioxidative, anti-inflammatory, and antithrombotic effects. Here we aimed to identify the metabolic profile of honokiol in mouse, rat, dog, monkey, and human hepatocytes and to characterize the enzymes responsible for the glucuronidation and sulfation of honokiol. Honokiol had a high hepatic extraction ratio in all five species, indicating that it was extensively metabolized. A total of 32 metabolites, including 17 common and 15 different metabolites, produced via glucuronidation, sulfation, and oxidation of honokiol allyl groups were tentatively identified using liquid chromatography-high resolution quadrupole Orbitrap mass spectrometry. Glucuronidation of honokiol to M8 (honokiol-4-glucuronide) and M9 (honokiol-2'-glucuronide) was the predominant metabolic pathway in hepatocytes of all five species; however, interspecies differences between 4- and 2'-glucuronidation of honokiol were observed. UGT1A1, 1A8, 1A9, 2B15, and 2B17 played major roles in M8 formation, whereas UGT1A7 and 1A9 played major roles in M9 formation. Human cDNA-expressed SULT1C4 played a major role in M10 formation (honokiol-2'-sulfate), whereas SULT1A1*1, 1A1*2, and 1A2 played major roles in M11 formation (honokiol-4-sulfate). In conclusion, honokiol metabolism showed interspecies differences.

  7. Differential Responding by Rhesus Monkeys (Macaca mulatta and Humans (Homo sapiens to Variable Outcomes in the Assurance Game

    Directory of Open Access Journals (Sweden)

    Audrey E. Parrish

    2014-08-01

    Full Text Available Behavioral flexibility in how one responds to variable partner play can be examined using economic coordination games in which subjects play against a variety of partners and therefore may need to alter their behavior to produce the highest payoff. But how do we study this behavioral flexibility once players have settled on a response? Here, we investigated how responding by rhesus monkeys (Macaca mulatta and humans (Homo sapiens playing a computerized single-player version of a coordination game, the Assurance game, changed as a function of the variable responses (Stag/Hare generated by multiple simulations (SIMs. We were interested in whether individuals could track and differentially respond to changing frequencies of Stag and Hare play by the SIMs, especially with regard to the payoff dominant (Stag-Stag outcome, something that could not be done with real partners as they quickly settled on the Stag response. For both monkeys and humans, there was a linear relationship between proportion of Stag play by the subject and the likelihood of the Stag choice by the SIM such that both species increased their use of Stag as the SIM increased its use of the Stag response. However, humans more closely matched their proportion of Stag responses to that of the SIM, whereas monkeys adopted a different, but equally effective, strategy of exploiting the higher-paying Stag alternative. These results suggest that monkeys and humans demonstrate sensitivity to a dynamic game environment in which they encounter variable contingencies for the same response options, although they may employ different strategies to maximize reward.

  8. The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance.

    Science.gov (United States)

    Innocenti, Giorgio M; Dyrby, Tim B; Andersen, Kasper Winther; Rouiller, Eric M; Caminiti, Roberto

    2017-06-01

    The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4-0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon diameters and conduction distance are <2 ms in the monkey and, by extrapolation, <4 ms in humans. This delay corresponds to the performance in Poffenberger's paradigm, a classical attempt to estimate central conduction delays, with a neuropsychological task. In both species, callosal cortico-striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported to dissociate syntax and prosody. The projection might originate from an overproduction of callosal projections in development, differentially pruned depending on species. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)

    2014-05-15

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  10. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    International Nuclear Information System (INIS)

    Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

    2014-01-01

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

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

    Directory of Open Access Journals (Sweden)

    Joy Gardner

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

  12. Dynamic Balance of Excitation and Inhibition in Human and Monkey Neocortex

    Science.gov (United States)

    Dehghani, Nima; Peyrache, Adrien; Telenczuk, Bartosz; Le van Quyen, Michel; Halgren, Eric; Cash, Sydney S.; Hatsopoulos, Nicholas G.; Destexhe, Alain

    2016-03-01

    Balance of excitation and inhibition is a fundamental feature of in vivo network activity and is important for its computations. However, its presence in the neocortex of higher mammals is not well established. We investigated the dynamics of excitation and inhibition using dense multielectrode recordings in humans and monkeys. We found that in all states of the wake-sleep cycle, excitatory and inhibitory ensembles are well balanced, and co-fluctuate with slight instantaneous deviations from perfect balance, mostly in slow-wave sleep. Remarkably, these correlated fluctuations are seen for many different temporal scales. The similarity of these computational features with a network model of self-generated balanced states suggests that such balanced activity is essentially generated by recurrent activity in the local network and is not due to external inputs. Finally, we find that this balance breaks down during seizures, where the temporal correlation of excitatory and inhibitory populations is disrupted. These results show that balanced activity is a feature of normal brain activity, and break down of the balance could be an important factor to define pathological states.

  13. Identification of putative substrates for cynomolgus monkey cytochrome P450 2C8 by substrate depletion assays with 22 human P450 substrates and inhibitors.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2016-07-01

    Cynomolgus monkeys are widely used in drug developmental stages as non-human primate models. Previous studies used 89 compounds to investigate species differences associated with cytochrome P450 (P450 or CYP) function that reported monkey specific CYP2C76 cleared 19 chemicals, and homologous CYP2C9 and CYP2C19 metabolized 17 and 30 human CYP2C9 and/or CYP2C19 substrates/inhibitors, respectively. In the present study, 22 compounds selected from viewpoints of global drug interaction guidances and guidelines were further evaluated to seek potential substrates for monkey CYP2C8, which is highly homologous to human CYP2C8 (92%). Amodiaquine, montelukast, quercetin and rosiglitazone, known as substrates or competitive inhibitors of human CYP2C8, were metabolically depleted by recombinant monkey CYP2C8 at relatively high rates. Taken together with our reported findings of the slow eliminations of amodiaquine and montelukast by monkey CYP2C9, CYP2C19 and CYP2C76, the present results suggest that these at least four chemicals may be good marker substrates for monkey CYP2C8. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Biomarkers of genetic damage in human populations exposed to pesticides

    International Nuclear Information System (INIS)

    Aiassa, Delia; Manas, Fernando; Bosch, Beatriz; Gentile, Natalia; Bernardi, Natali; Gorla, Nora

    2012-01-01

    The effect of pesticides on human, animal and environmental health has been cause of concern in the scientific community for a long time. Numerous studies have reported that pesticides are not harmless and that their use can lead to harmful biological effects in the medium and long term, in exposed human and animals, and their offspring. The importance of early detection of genetic damage is that it allows us to take the necessary measures to reduce or eliminate the exposure to the deleterious agent when damage is still reversible, and thus to prevent and to diminish the risk of developing tumors or other alterations. In this paper we reviewed the main concepts in the field, the usefulness of genotoxicity studies and we compiled studies performed during the last twenty years on genetic monitoring of people occupationally exposed to pesticides. we think that genotoxicity tests, including that include chromosomal aberrations, micronucleus, sister chromatid exchanges and comet assays, should be considered as essential tools in the implementation of complete medical supervision for people exposed to potential environmental pollutants, particularly for those living in the same place as others who were others have already developed some type of malignancy. This action is particularly important at early stages to prevent the occurrence of tumors, especially from environmental origins.

  15. Cerebral Anatomy of the Spider Monkey Ateles Geoffroyi Studied Using Magnetic Resonance Imaging. First Report: a Comparative Study with the Human Brain Homo Sapiens

    OpenAIRE

    Chico-Ponce de León, Fernando; Platas-Neri, Diana; Muñoz-Delgado, Jairo; Santillán-Doherty, Ana María; Arenas-Rosas, Rita; Trejo, David; Conde, Rubén; Ojeda-Flores, Rafael; Campos-Romo, Aurelio; Castro-Sierra, Eduardo; Cervantes, Juan José; Braun, Marc

    2009-01-01

    The objective of the present qualitative study was to analyze the morphological aspects of the inner cerebral anatomy of two species of primates, using magnetic resonance images (MRI): spider monkey (A. geoffroyi) and human (H. sapiens), on the basis of a comparative study of the cerebral structures of the two species, focusing upon the brain of the spider monkey and, primarily, its limbic system. In spite of being an endemic Western hemisphere species, a fact which is by its own right intere...

  16. Kinetic analysis of interactions of paraoxon and oximes with human, Rhesus monkey, swine, rabbit, rat and guinea pig acetylcholinesterase.

    Science.gov (United States)

    Worek, Franz; Aurbek, Nadine; Wille, Timo; Eyer, Peter; Thiermann, Horst

    2011-01-15

    Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneous and oxime-induced reactivation kinetics of the pesticide paraoxon, serving as a model compound for diethyl-OP, and the oximes obidoxime, pralidoxime, HI 6 and MMB-4 with human, Rhesus monkey, swine, rabbit, rat and guinea pig erythrocyte AChE. Comparable results were obtained with human and monkey AChE. Differences between human, swine, rabbit, rat and guinea pig AChE were determined for the inhibition and reactivation kinetics. A six-fold difference of the inhibitory potency of paraoxon with human and guinea pig AChE was recorded while only moderate differences of the reactivation constants between human and animal AChE were determined. Obidoxime was by far the most effective reactivator with all tested species. Only minor species differences were found for the aging and spontaneous reactivation kinetics. The results of the present study underline the necessity to determine the inhibition, aging and reactivation kinetics in vitro as a basis for the development of meaningful therapeutic animal models, for the proper assessment of in vivo animal data and for the extrapolation of animal data to humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Enhanced expression of transferrin receptor confers UV-resistance in human and monkey cells

    International Nuclear Information System (INIS)

    Chen, Zheng; Nomura, Jun; Suzuki, Toshikazu; Suzuki, Nobuo

    2005-01-01

    One of the most intriguing biological subjects is cell-surface molecules that regulate the susceptibility of human cells to cell-killing effects after irradiation with far-ultraviolet light (UV, principally 254 nm wavelength). Human RSa cells have unusual sensitivity to UV-induced cell-killing. We searched for molecules on the cell-surface of RSa cells that were present in different amounts as compared to a variant of these cells, UV r -1 cells, which have increased resistance to UV cell-killing. Among the 21 molecules examined, the amount of transferrin receptor (TfR) protein was found to be 2-fold higher in UV r -1 cells compared with in RSa cells. The amounts of this protein were also higher in the UV-resistant hematopoietic cell lines, CEM6 and Daudi, as compared to the UV-sensitive cell lines, Molt4 and 697. Culturing of UV r -1 cells in a medium containing anti-transferrin antibodies resulted in sensitization of the cells to UV cell-killing as demonstrated by colony formation assay. Similar results were observed by treatment of the cells with TfR siRNA. In contrast, overexpression of TfR protein led to a resistance to UV cell-killing in RSa cells and monkey COS7 cells as demonstrated by both colony formation and apoptosis assay. In TfR-overexpressing cells, reduction of p53 and Bax protein was observed after UV-irradiation. Thus, TfR expression appears to be involved in the regulation of UV-resistance, possibly via modulation of the amount of p53 and Bax protein. (author)

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

    Directory of Open Access Journals (Sweden)

    Albert Lalremruata

    2015-09-01

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

  19. Third-party social evaluations of humans by monkeys and dogs.

    Science.gov (United States)

    Anderson, James R; Bucher, Benoit; Chijiiwa, Hitomi; Kuroshima, Hika; Takimoto, Ayaka; Fujita, Kazuo

    2017-11-01

    Developmental psychologists are increasingly interested in young children's evaluations of individuals based on third-party interactions. Studies have shown that infants react negatively to agents who display harmful intentions toward others, and to those who behave unfairly. We describe experimental studies of capuchin monkeys' and pet dogs' differential reactions to people who are helpful or unhelpful in third-party contexts, and monkeys' responses to people who behave unfairly in exchanges of objects with a third party. We also present evidence that capuchin monkeys monitor the context of failures to help and violations of reciprocity, and that intentionality is one factor underlying their social evaluations of individuals whom they see interacting with others. We conclude by proposing some questions for studies of nonhuman species' third party-based social evaluations. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kriti Tyagi

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    Kennedy, Erica Hoy; Fragaszy, Dorothy M

    2008-05-01

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

  5. Metabolic fate of the beta-blocker 14C-bupranolol in humans, dogs, and rhesus monkeys

    International Nuclear Information System (INIS)

    Waller, A.R.; Chasseaud, L.F.; Bonn, R.; Taylor, T.; Darragh, A.; Girkin, R.; Down, W.H.; Doyle, E.

    1982-01-01

    An oral dose of 14 C-bupranolol hydrochloride was well absorbed by humans (100 mg), dogs (1 mg/kg), and rhesus monkeys (1 mg/kg). These species excreted 87.8 and 3.5%, 81.1 and 13.6%, and 92.9 ad 5.0% of the 14 C-dose in urine and feces, respectively, mainly in 12 or 24 hr. Mean plasma levels of 14 C, which appeared to be almost entirely associated with a single metabolite, peaked at 1 hr in humans (1.6 micrograms-equiv./ml) and dogs (1.6 micrograms-/ml) and at 2 hr in monkeys (0.8 micrograms-equiv./ml). Concentrations initially declined with similar half-lives (about 1.5 hr) in all three species. Biliary excretion of 14 C occurred in the animal species in which also peak plasma 14 C levels exceeded those in most tissues. Unchanged bupranolol was not detected in plasma; the peak plasma and urinary 14 C was mainly associated (greater than 90% in humans) with a metabolite produced by oxidation of the aromatic ring methyl group of bupranolol to a carboxyl group

  6. Avalanche analysis from multi-electrode ensemble recordings in cat, monkey and human cerebral cortex during wakefulness and sleep.

    Directory of Open Access Journals (Sweden)

    Nima eDehghani

    2012-08-01

    Full Text Available Self-organized critical states are found in many natural systems, from earthquakes to forest fires, they have also been observed in neural systems, particularly, in neuronal cultures. However, the presence of critical states in the awake brain remains controversial. Here, we compared avalanche analyses performed on different in vivo preparations during wakefulness, slow-wave sleep and REM sleep, using high-density electrode arrays in cat motor cortex (96 electrodes, monkey motor cortex and premotor cortex and human temporal cortex (96 electrodes in epileptic patients. In neuronal avalanches defined from units (up to 160 single units, the size of avalanches never clearly scaled as power-law, but rather scaled exponentially or displayed intermediate scaling. We also analyzed the dynamics of local field potentials (LFPs and in particular LFP negative peaks (nLFPs among the different electrodes (up to 96 sites in temporal cortex or up to 128 sites in adjacent motor and pre-motor cortices. In this case, the avalanches defined from nLFPs displayed power-law scaling in double logarithmic representations, as reported previously in monkey. However, avalanche defined as positive LFP (pLFP peaks, which are less directly related to neuronal firing, also displayed apparent power-law scaling. Closer examination of this scaling using the more reliable cumulative distribution function (CDF and other rigorous statistical measures, did not confirm power-law scaling. The same pattern was seen for cats, monkey and human, as well as for different brain states of wakefulness and sleep. We also tested other alternative distributions. Multiple exponential fitting yielded optimal fits of the avalanche dynamics with bi-exponential distributions. Collectively, these results show no clear evidence for power-law scaling or self-organized critical states in the awake and sleeping brain of mammals, from cat to man.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  8. Detection of Signal Regulatory Protein α in Saimiri sciureus (Squirrel Monkey) by Anti-Human Monoclonal Antibody

    Science.gov (United States)

    de Souza, Hugo Amorim dos Santos; Costa-Correa, Edmar Henrique; Bianco-Junior, Cesare; Andrade, Márcia Cristina Ribeiro; Lima-Junior, Josué da Costa; Pratt-Riccio, Lilian Rose; Daniel-Ribeiro, Cláudio Tadeu; Totino, Paulo Renato Rivas

    2017-01-01

    Non-human primates (NHP) are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as Saimiri sciureus, is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules. In this context and considering the key role of inhibitory immunoreceptors—such as the signal regulatory protein α (SIRPα)—in the regulation of immune responses, in the present study, we attempted to evaluate the ability of anti-human SIRPα monoclonal antibodies to recognize SIRPα in antigen-presenting S. sciureus peripheral blood mononuclear cells (PBMC). As shown by flow cytometry analysis, the profile of anti-SIRPα staining as well as the levels of SIRPα-positive cells in PBMC from S. sciureus were similar to those observed in human PBMC. Furthermore, using anti-SIRPα monoclonal antibody, it was possible to detect a decrease of the SIRPα levels on surface of S. sciureus cells after in vitro stimulation with lipopolysaccharides. Finally, using computed-based analysis, we observed a high degree of conservation of SIRPα across six species of primates and the presence of shared epitopes in the extracellular domain between humans and Saimiri genus that could be targeted by antibodies. In conclusion, we have identified a commercially available anti-human monoclonal antibody that is able to detect SIRPα of S. sciureus monkeys and that, therefore, can facilitate the study of the immunomodulatory role of SIRPα when S. sciureus is used as a model. PMID:29312325

  9. Detection of Signal Regulatory Protein α in Saimiri sciureus (Squirrel Monkey by Anti-Human Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Hugo Amorim dos Santos de Souza

    2017-12-01

    Full Text Available Non-human primates (NHP are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as Saimiri sciureus, is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules. In this context and considering the key role of inhibitory immunoreceptors—such as the signal regulatory protein α (SIRPα—in the regulation of immune responses, in the present study, we attempted to evaluate the ability of anti-human SIRPα monoclonal antibodies to recognize SIRPα in antigen-presenting S. sciureus peripheral blood mononuclear cells (PBMC. As shown by flow cytometry analysis, the profile of anti-SIRPα staining as well as the levels of SIRPα-positive cells in PBMC from S. sciureus were similar to those observed in human PBMC. Furthermore, using anti-SIRPα monoclonal antibody, it was possible to detect a decrease of the SIRPα levels on surface of S. sciureus cells after in vitro stimulation with lipopolysaccharides. Finally, using computed-based analysis, we observed a high degree of conservation of SIRPα across six species of primates and the presence of shared epitopes in the extracellular domain between humans and Saimiri genus that could be targeted by antibodies. In conclusion, we have identified a commercially available anti-human monoclonal antibody that is able to detect SIRPα of S. sciureus monkeys and that, therefore, can facilitate the study of the immunomodulatory role of SIRPα when S. sciureus is used as a model.

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

    Directory of Open Access Journals (Sweden)

    Alex G. Lee

    2016-06-01

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

  11. Identification of Phylogenetic Position in the Chlamydiaceae Family for Chlamydia Strains Released from Monkeys and Humans with Chlamydial Pathology

    Directory of Open Access Journals (Sweden)

    Alexander Karaulov

    2010-01-01

    Full Text Available Based on the results of the comparative analysis concerning relatedness and evolutional difference of the 16S–23S nucleotide sequences of the middle ribosomal cluster and 23S rRNA I domain, and based on identification of phylogenetic position for Chlamydophila pneumoniae and Chlamydia trichomatis strains released from monkeys, relatedness of the above stated isolates with similar strains released from humans and with strains having nucleotide sequences presented in the GenBank electronic database has been detected for the first time ever. Position of these isolates in the Chlamydiaceae family phylogenetic tree has been identified. The evolutional position of the investigated original Chlamydia and Chlamydophila strains close to analogous strains from the Gen-Bank electronic database has been demonstrated. Differences in the 16S–23S nucleotide sequence of the middle ribosomal cluster and 23S rRNA I domain of plasmid and nonplasmid Chlamydia trachomatis strains released from humans and monkeys relative to different genotype groups (group B-B, Ba, D, Da, E, L1, L2, L2a; intermediate group-F, G, Ga have been revealed for the first time ever. Abnormality in incA chromosomal gene expression resulting in Chlamydia life development cycle disorder, and decrease of Chlamydia virulence can be related to probable changes in the nucleotide sequence of the gene under consideration

  12. Evidence for the speed-value trade-off: human and monkey decision making is magnitude sensitive.

    Science.gov (United States)

    Pirrone, Angelo; Azab, Habiba; Hayden, Benjamin Y; Stafford, Tom; Marshall, James A R

    2018-04-01

    Complex natural systems from brains to bee swarms have evolved to make adaptive multifactorial decisions. Recent theoretical and empirical work suggests that many evolved systems may take advantage of common motifs across multiple domains. We are particularly interested in value sensitivity (i.e., sensitivity to the magnitude or intensity of the stimuli or reward under consideration) as a mechanism to resolve deadlocks adaptively. This mechanism favours long-term reward maximization over accuracy in a simple manner, because it avoids costly delays associated with ambivalence between similar options; speed-value trade-offs have been proposed to be evolutionarily advantageous for many kinds of decision. A key prediction of the value-sensitivity hypothesis is that choices between equally-valued options will proceed faster when the options have a high value than when they have a low value. However, value-sensitivity is not part of idealised choice models such as diffusion to bound. Here we examine two different choice behaviours in two different species, perceptual decisions in humans and economic choices in rhesus monkeys, to test this hypothesis. We observe the same value sensitivity in both human perceptual decisions and monkey value-based decisions. These results endorse the idea that neural decision systems make use of the same basic principle of value-sensitivity in order to resolve costly deadlocks and thus improve long-term reward intake.

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

    Science.gov (United States)

    1994-01-01

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

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

    OpenAIRE

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

    1986-01-01

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

  15. Mental transformations of spatial stimuli in humans and in monkeys: Rotation vs. translocation

    Czech Academy of Sciences Publication Activity Database

    Nekovářová, Tereza; Nedvídek, J.; Klement, Daniel; Rokyta, R.; Bureš, Jan

    2013-01-01

    Roč. 240, Mar 1 (2013), s. 182-191 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA ČR(CZ) GAP303/12/1464; GA MZd(CZ) NT13386 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : rhesus monkey * cognition * spatial task * rotation Subject RIV: FH - Neurology Impact factor: 3.391, year: 2013

  16. Molecular cloning and characterization of rhesus monkey platelet glycoprotein Ibα, a major ligand-binding subunit of GPIb-IX-V complex.

    Science.gov (United States)

    Qiao, Jianlin; Shen, Yang; Shi, Meimei; Lu, Yanrong; Cheng, Jingqiu; Chen, Younan

    2014-05-01

    Through binding to von Willebrand factor (VWF), platelet glycoprotein (GP) Ibα, the major ligand-binding subunit of the GPIb-IX-V complex, initiates platelet adhesion and aggregation in response to exposed VWF or elevated fluid-shear stress. There is little data regarding non-human primate platelet GPIbα. This study cloned and characterized rhesus monkey (Macaca Mullatta) platelet GPIbα. DNAMAN software was used for sequence analysis and alignment. N/O-glycosylation sites and 3-D structure modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS-MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin-induced platelet aggregation. Rhesus monkey GPIbα contains 2,268 nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey GPIbα nucleotide and protein sequences share 93.27% and 89.20% homology respectively, with human. Sequences encoding the leucine-rich repeats of rhesus monkey GPIbα share strong similarity with human, whereas PEST sequences and N/O-glycosylated residues vary. The GPIbα-binding residues for thrombin, filamin A and 14-3-3ζ are highly conserved between rhesus monkey and human. Platelet function analysis revealed monkey and human platelets respond similarly to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin where human platelets achieved 76% aggregation. However, monkey platelets aggregated in response to higher ristocetin doses. Monkey GPIbα shares strong homology with human GPIbα, however there are some differences in rhesus monkey platelet activation through GPIbα engagement, which need to be considered when using rhesus monkey platelet to investigate platelet GPIbα function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Autoshaping in Japanese Monkeys (Macaca Fuscata)

    OpenAIRE

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

    1992-01-01

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

  18. Olfactory sensitivity for sperm-attractant aromatic aldehydes: a comparative study in human subjects and spider monkeys.

    Science.gov (United States)

    Kjeldmand, Luna; Salazar, Laura Teresa Hernandez; Laska, Matthias

    2011-01-01

    Using a three-alternative forced-choice ascending staircase procedure, we determined olfactory detection thresholds in 20 human subjects for seven aromatic aldehydes and compared them to those of four spider monkeys tested in parallel using an operant conditioning paradigm. With all seven odorants, both species detected concentrations lyral, and 3-phenylpropanal. No significant correlation between presence/absence of an oxygen-containing moiety attached to the benzene ring or presence/absence of an additional alkyl group next to the functional aldehyde group, and olfactory sensitivity was found in any of the species. However, the presence of a tertiary butyl group in para position (relative to the functional aldehyde group) combined with a lack of an additional alkyl group next to the functional aldehyde group may be responsible for the finding that both species were most sensitive to bourgeonal.

  19. Sensory-specific amnesia and hypoemotionality in humans and monkeys: gateway for developing a hodology of memory.

    Science.gov (United States)

    Ross, Elliott D

    2008-09-01

    Amnesia is a dramatic clinical syndrome caused by diverse pathologies and lesion localizations. Although amnesia is typically screened for by clinicians using verbal stimuli, amnestic syndromes have been described that do not impair verbal memory and may be confined to a single sensory system or a dominant or highly lateralized sensory function. Thus, the functional-anatomic basis for various types of amnestic disorders is complex and, in most instances, better understood as a disconnection syndrome rather than a primary processing deficit. Using the clinical disorder of sensory-specific visual amnesia in humans as a springboard, a hodological model for understanding the various types of amnestic syndromes encountered in the clinic and those produced by discrete experimental lesions in monkeys is offered. The model is then expanded to encompass memory functions, in general, including agnostic deficits and the role of prefrontal cortex in learning and remembering.

  20. Physiology and physiopathology of central type Benzodiazepine receptors: Study in the monkey and in human brain using positron emission tomography

    International Nuclear Information System (INIS)

    Hantraye, P.

    1987-01-01

    A new non-invasive technique that allows to study in a living subject central type benzodiazepine receptors is developed. A combined approach is applied using a specific positron-emitting radiotracer for the in vivo labelling of the receptors and positron emission tomography allowing, by external detection, a quantitative determination of tissue radioactivity. The radioligand used for the in vivo labelling of benzodiazepine receptors is the antagonist RO 15-1788 labelled with carbon 11. The various stages of the study are described: in vivo characterization in the monkey of central type benzodiazepine receptors; characterization of central type benzodiazepine receptors in human brain using selective molecules for the BZ1 benzodiazepine subclass; demonstration of the heterogeneity of central type benzodiazepine receptors in the brain; study of pathological alteration of benzodiazepine receptors in experimental epilepsy [fr

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-01

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

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

    International Nuclear Information System (INIS)

    Ryan, Patricia C.; Sleeman, Matthew A.; Rebelatto, Marlon; Wang, Bing; Lu, Hong; Chen, Xiaomin; Wu, Chi-Yuan; Hinrichs, Mary Jane; Roskos, Lorin; Towers, Heidi; McKeever, Kathleen; Dixit, Rakesh

    2014-01-01

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

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

    Science.gov (United States)

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

    2009-12-01

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

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

    OpenAIRE

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

    2011-01-01

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

  5. Novel Monoclonal Antibody LpMab-17 Developed by CasMab Technology Distinguishes Human Podoplanin from Monkey Podoplanin.

    Science.gov (United States)

    Kato, Yukinari; Ogasawara, Satoshi; Oki, Hiroharu; Honma, Ryusuke; Takagi, Michiaki; Fujii, Yuki; Nakamura, Takuro; Saidoh, Noriko; Kanno, Hazuki; Umetsu, Mitsuo; Kamata, Satoshi; Kubo, Hiroshi; Yamada, Mitsuhiro; Sawa, Yoshihiko; Morita, Kei-Ichi; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika Kato

    2016-04-01

    Podoplanin (PDPN) is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain in its N-terminus. Among the three PLAG domains, O-glycan on Thr52 of PLAG3 is critical for the binding with C-type lectin-like receptor-2 (CLEC-2) and is essential for platelet-aggregating activity of PDPN. Although many anti-PDPN monoclonal antibodies (mAbs) have been established, almost all mAbs bind to PLAG domains. We recently established CasMab technology to produce mAbs against membranous proteins. Using CasMab technology, we produced a novel anti-PDPN mAb, LpMab-17, which binds to non-PLAG domains. LpMab-17 clearly detected endogenous PDPN of cancer cells and normal cells in Western-blot, flow cytometry, and immunohistochemistry. LpMab-17 recognized glycan-deficient PDPN in flow cytometry, indicating that the interaction between LpMab-17 and PDPN is independent of its glycosylation. The minimum epitope of LpMab-17 was identified as Gly77-Asp82 of PDPN using enzyme-linked immunosorbent assay. Of interest, LpMab-17 did not bind to monkey PDPN, whereas the homology is 94% between human PDPN and monkey PDPN, indicating that the epitope of LpMab-17 is unique compared with the other anti-PDPN mAbs. The combination of different epitope-possessing mAbs could be advantageous for the PDPN-targeting diagnosis or therapy.

  6. Hepatobiliary Clearance Prediction: Species Scaling From Monkey, Dog, and Rat, and In Vitro-In Vivo Extrapolation of Sandwich-Cultured Human Hepatocytes Using 17 Drugs.

    Science.gov (United States)

    Kimoto, Emi; Bi, Yi-An; Kosa, Rachel E; Tremaine, Larry M; Varma, Manthena V S

    2017-09-01

    Hepatobiliary elimination can be a major clearance pathway dictating the pharmacokinetics of drugs. Here, we first compared the dose eliminated in bile in preclinical species (monkey, dog, and rat) with that in human and further evaluated single-species scaling (SSS) to predict human hepatobiliary clearance. Six compounds dosed in bile duct-cannulated (BDC) monkeys showed biliary excretion comparable to human; and the SSS of hepatobiliary clearance with plasma fraction unbound correction yielded reasonable predictions (within 3-fold). Although dog SSS also showed reasonable predictions, rat overpredicted hepatobiliary clearance for 13 of 24 compounds. Second, we evaluated the translatability of in vitro sandwich-cultured human hepatocytes (SCHHs) to predict human hepatobiliary clearance for 17 drugs. For drugs with no significant active uptake in SCHH studies (i.e., with or without rifamycin SV), measured intrinsic biliary clearance was directly scalable with good predictability (absolute average fold error [AAFE] = 1.6). Drugs showing significant active uptake in SCHH, however, showed improved predictability when scaled based on extended clearance term (AAFE = 2.0), which incorporated sinusoidal uptake along with a global scaling factor for active uptake and the canalicular efflux clearance. In conclusion, SCHH is a useful tool to predict human hepatobiliary clearance, whereas BDC monkey model may provide further confidence in the prospective predictions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Monkey Business

    Science.gov (United States)

    Blackwood, Christine Horvatis

    2012-01-01

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

  8. Direct assessment of cumulative aryl hydrocarbon receptor agonist activity in sera from experimentally exposed mice and environmentally exposed humans

    DEFF Research Database (Denmark)

    Schlezinger, Jennifer J; Bernard, Pamela L; Haas, Amelia

    2010-01-01

    (PCB)-exposed Faroe Islanders using an AhR-driven reporter cell line. To validate relationships between serum AhR agonist levels and biological outcomes, AhR agonist activity in mouse sera correlated with toxic end points. AhR agonist activity in unmanipulated ("neat") human sera was compared......, was associated with the frequency of recent pilot whale dinners, but did not correlate with levels of PCBs quantified by GC/MS. Surprisingly, significant "baseline" AhR activity was found in commercial human sera. CONCLUSIONS: An AhR reporter assay revealed cumulative levels of AhR activation potential in neat...

  9. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  10. Medicinal plants in the diet of woolly spider monkeys (Brachyteles arachnoides, E. Geoffroy, 1806 – a bio-rational for the search of new medicines for human use?

    Directory of Open Access Journals (Sweden)

    Liége M. Petroni

    Full Text Available ABSTRACT The present study aimed to compare the plant food diet of woolly spider monkeys (Brachyteles arachnoides inhabiting Intervales State Park in São Paulo, Brazil, with medicinal plant species used by humans in the surrounding areas of the park. The diet of a group of woolly spider monkeys living in an Atlantic forest area was recorded during 43 months of fieldwork. Fifty-three species (87 food items were recorded. Plant specimens were collected and identified at the University of São Paulo and the Botanical Institute of São Paulo State. Using semi-structured interviews, ethnomedicinal data were also collected from four preselected respondents regarding the human therapeutic value of these plants. The study showed that 24.5% (13/53 of these species are used by residents around the park for medicinal purposes. Of these thirteen, seven species also have validated pharmacological properties, and three are utilized by local residents for similar medicinal purposes. Overlap in the plant food/medicinal diet of woolly spider monkey populations elsewhere were also noted, suggesting potential overlap in their medicinal value for humans and primates. The similarities between the ingestion of plants by primates and their medicinal use by humans provide a bio-rational for the search of bioactive plants in the primate diet. Further detailed investigation of their pharmacological and phytochemical value is warranted.

  11. On Loss Aversion in Capuchin Monkeys

    Science.gov (United States)

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

    2008-01-01

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

  12. Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography

    Science.gov (United States)

    Koller, Kristin; Bultitude, Janet H.; Mullins, Paul; Ward, Robert; Mitchell, Anna S.; Bell, Andrew H.

    2015-01-01

    It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species. PMID:26224780

  13. The effect of dimerizing domains and basic residues on in vitro and in vivo assembly of Mason-Pfizer monkey virus and Human immunodeficiency virus

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Karolína; Hadravová, Romana; Štokrová, Jitka; Tůma, R.; Ruml, T.; Pichová, Iva; Rumlová, Michaela

    2010-01-01

    Roč. 84, č. 4 (2010), s. 1977-1988 ISSN 0022-538X R&D Projects: GA MŠk 1M0508; GA ČR GA204/09/1388 Grant - others:EUROCORES(XE) ERAS-CT-2003-980409 Institutional research plan: CEZ:AV0Z40550506 Keywords : Mason-Pfizer Monkey Virus * Human Immunodeficiency Virus * assembly * NC Subject RIV: CC - Organic Chemistry Impact factor: 5.189, year: 2010

  14. [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    International Nuclear Information System (INIS)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars; Guilloteau, Denis; Emond, Patrick

    2003-01-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [ 11 C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [ 11 C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [ 11 C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [ 11 C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [ 11 C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  15. [{sup 11}C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 17176, Stockholm (Sweden); Guilloteau, Denis; Emond, Patrick [INSERM U316 Universite Francois Rabelais, Tours (France)

    2003-09-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2{beta}-carbomethoxy-3{beta}-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [{sup 11}C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/{mu}mol). [{sup 11}C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled {beta}-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [{sup 11}C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [{sup 11}C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [{sup 11}C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  16. "Unwilling" versus "Unable": Capuchin Monkeys' ("Cebus Apella") Understanding of Human Intentional Action

    Science.gov (United States)

    Phillips, Webb; Barnes, Jennifer L.; Mahajan, Neha; Yamaguchi, Mariko; Santos, Laurie R.

    2009-01-01

    A sensitivity to the intentions behind human action is a crucial developmental achievement in infants. Is this intention reading ability a unique and relatively recent product of human evolution and culture, or does this capacity instead have roots in our non-human primate ancestors? Recent work by Call and colleagues (2004) lends credence to the…

  17. Highly Efficient Differentiation and Enrichment of Spinal Motor Neurons Derived from Human and Monkey Embryonic Stem Cells

    Science.gov (United States)

    Wada, Tamaki; Honda, Makoto; Minami, Itsunari; Tooi, Norie; Amagai, Yuji; Nakatsuji, Norio; Aiba, Kazuhiro

    2009-01-01

    Background There are no cures or efficacious treatments for severe motor neuron diseases. It is extremely difficult to obtain naïve spinal motor neurons (sMNs) from human tissues for research due to both technical and ethical reasons. Human embryonic stem cells (hESCs) are alternative sources. Several methods for MN differentiation have been reported. However, efficient production of naïve sMNs and culture cost were not taken into consideration in most of the methods. Methods/Principal Findings We aimed to establish protocols for efficient production and enrichment of sMNs derived from pluripotent stem cells. Nestin+ neural stem cell (NSC) clusters were induced by Noggin or a small molecule inhibitor of BMP signaling. After dissociation of NSC clusters, neurospheres were formed in a floating culture containing FGF2. The number of NSCs in neurospheres could be expanded more than 30-fold via several passages. More than 33% of HB9+ sMN progenitor cells were observed after differentiation of dissociated neurospheres by all-trans retinoic acid (ATRA) and a Shh agonist for another week on monolayer culture. HB9+ sMN progenitor cells were enriched by gradient centrifugation up to 80% purity. These HB9+ cells differentiated into electrophysiologically functional cells and formed synapses with myotubes during a few weeks after ATRA/SAG treatment. Conclusions and Significance The series of procedures we established here, namely neural induction, NSC expansion, sMN differentiation and sMN purification, can provide large quantities of naïve sMNs derived from human and monkey pluripotent stem cells. Using small molecule reagents, reduction of culture cost could be achieved. PMID:19701462

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

    Science.gov (United States)

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

    2016-10-01

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

  19. A specialized face-processing model inspired by the organization of monkey face patches explains several face-specific phenomena observed in humans.

    Science.gov (United States)

    Farzmahdi, Amirhossein; Rajaei, Karim; Ghodrati, Masoud; Ebrahimpour, Reza; Khaligh-Razavi, Seyed-Mahdi

    2016-04-26

    Converging reports indicate that face images are processed through specialized neural networks in the brain -i.e. face patches in monkeys and the fusiform face area (FFA) in humans. These studies were designed to find out how faces are processed in visual system compared to other objects. Yet, the underlying mechanism of face processing is not completely revealed. Here, we show that a hierarchical computational model, inspired by electrophysiological evidence on face processing in primates, is able to generate representational properties similar to those observed in monkey face patches (posterior, middle and anterior patches). Since the most important goal of sensory neuroscience is linking the neural responses with behavioral outputs, we test whether the proposed model, which is designed to account for neural responses in monkey face patches, is also able to predict well-documented behavioral face phenomena observed in humans. We show that the proposed model satisfies several cognitive face effects such as: composite face effect and the idea of canonical face views. Our model provides insights about the underlying computations that transfer visual information from posterior to anterior face patches.

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

    Science.gov (United States)

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

    2018-03-29

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

  1. Double-bouquet cells in the monkey and human cerebral cortex with special reference to areas 17 and 18.

    Science.gov (United States)

    DeFelipe, Javier; Ballesteros-Yáñez, Inmaculada; Inda, Maria Carmen; Muñoz, Alberto

    2006-01-01

    The detailed microanatomical study of the human cerebral cortex began in 1899 with the experiments of Santiago Ramón y Cajal, who applied the Golgi method to define the structure of the visual, motor, auditory and olfactory cortex. In the first article of this series, he described a special type of interneuron in the visual cortex capable of exerting its influence in the vertical dimension. These neurons are now more commonly referred to as double-bouquet cells (DBCs). The DBCs are readily distinguished owing to their characteristic axons that give rise to tightly interwoven bundles of long, vertically oriented axonal collaterals resembling a horsetail (DBC horsetail). Nevertheless, the most striking characteristic of these neurons is that they are so numerous and regularly distributed that the DBC horsetails form a microcolumnar structure. In addition, DBCs establish hundreds of inhibitory synapses within a very narrow column of cortical tissue. These features have generated considerable interest in DBCs over recent years, principally among those researchers interested in the analysis of cortical circuits. In the present chapter, we shall discuss the morphology, synaptic connections and neurochemical features of DBCs that have been defined through the study of these cells in different cortical areas and species. We will mainly consider the immunocytochemical studies of DBCs that have been carried out in the visual cortex (areas 17 and 18) of human and macaque monkey. We will see that there are important differences in the morphology, number and distribution of DBC horsetails between areas 17 and 18 in the primate. This suggests important differences in the microcolumnar organization between these areas, the functional significance of which awaits detailed correlative physiological and microanatomical studies.

  2. Basic Math in Monkeys and College Students

    OpenAIRE

    Beran, Michael J

    2008-01-01

    Recent behavioral and neuroimaging studies with humans and monkeys provide compelling evidence of shared numerical capacities across species. Our understanding of the emergence of human mathematical competence is well-served by these kinds of comparative assessments.

  3. Mixed-complexity artificial grammar learning in humans and macaque monkeys: evaluating learning strategies.

    Science.gov (United States)

    Wilson, Benjamin; Smith, Kenny; Petkov, Christopher I

    2015-03-01

    Artificial grammars (AG) can be used to generate rule-based sequences of stimuli. Some of these can be used to investigate sequence-processing computations in non-human animals that might be related to, but not unique to, human language. Previous AG learning studies in non-human animals have used different AGs to separately test for specific sequence-processing abilities. However, given that natural language and certain animal communication systems (in particular, song) have multiple levels of complexity, mixed-complexity AGs are needed to simultaneously evaluate sensitivity to the different features of the AG. Here, we tested humans and Rhesus macaques using a mixed-complexity auditory AG, containing both adjacent (local) and non-adjacent (longer-distance) relationships. Following exposure to exemplary sequences generated by the AG, humans and macaques were individually tested with sequences that were either consistent with the AG or violated specific adjacent or non-adjacent relationships. We observed a considerable level of cross-species correspondence in the sensitivity of both humans and macaques to the adjacent AG relationships and to the statistical properties of the sequences. We found no significant sensitivity to the non-adjacent AG relationships in the macaques. A subset of humans was sensitive to this non-adjacent relationship, revealing interesting between- and within-species differences in AG learning strategies. The results suggest that humans and macaques are largely comparably sensitive to the adjacent AG relationships and their statistical properties. However, in the presence of multiple cues to grammaticality, the non-adjacent relationships are less salient to the macaques and many of the humans. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine

    International Nuclear Information System (INIS)

    Velsor, Leonard W.; Kovacevic, Miro; Goldstein, Mark; Leitner, Heather M.; Lewis, William; Day, Brian J.

    2004-01-01

    The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use

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

    Directory of Open Access Journals (Sweden)

    John K Thuita

    2015-02-01

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

  6. An Enhanced Pre- and Postnatal Development Study in Cynomolgus Monkeys with Tabalumab: A Human IgG4 Monoclonal Antibody.

    Science.gov (United States)

    Breslin, William J; Hilbish, Kim G; Martin, Jennifer A; Halstead, Carolyn A; Newcomb, Deanna L; Chellman, Gary J

    2015-06-01

    Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B-cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by subcutaneous injection to presumed pregnant cynomolgus monkeys (16-19 per group) every 2 weeks from gestation day (GD) 20 to 22 until parturition at doses of 0, 0.3, or 30 mg/kg. Evaluations in mothers and infants included clinical signs, body weight, toxicokinetics, blood lymphocyte phenotyping, T-cell-dependent antibody response (infants only), antitherapeutic antibody (ATA), organ weights (infants only), and gross and microscopic histopathology. Infants were also examined for external and visceral morphologic and neurobehavioral development. There were no adverse tabalumab-related effects on maternal or infant endpoints. An expected pharmacological decrease in peripheral blood B-lymphocytes occurred in adults and infants; however, B-cell recovery was evident by PND154 in adults and infants at 0.3 mg/kg and by PND204 in infants at 30 mg/kg. At 30 mg/kg, a reduced IgM antibody response to T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was observed following primary immunization. Following secondary KLH immunization, all infants in both dose groups mounted anti-KLH IgM and IgG antibody responses similar to control. Placental and mammary transfer of tabalumab was demonstrated. In conclusion, the no-observed-adverse-effect level for maternal and developmental toxicity was 30 mg/kg, the highest dose tested. Exposures at 30 mg/kg provide a margin of safety of 16× the anticipated clinical exposure. © 2015 Wiley Periodicals, Inc.

  7. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Science.gov (United States)

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  8. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

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

  9. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2015-03-01

    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  11. The relative use of proximity, shape similarity, and orientation as visual perceptual grouping cues in tufted capuchin monkeys (Cebus apella) and humans (Homo sapiens).

    Science.gov (United States)

    Spinozzi, Giovanna; De Lillo, Carlo; Truppa, Valentina; Castorina, Giulia

    2009-02-01

    Recent experimental results suggest that human and nonhuman primates differ in how they process visual information to assemble component parts into global shapes. To assess whether some of the observed differences in perceptual grouping could be accounted for by the prevalence of different grouping factors in different species, we carried out 2 experiments designed to evaluate the relative use of proximity, similarity of shape, and orientation as grouping cues in humans (Homo sapiens) and capuchin monkeys (Cebus apella). Both species showed similarly high levels of accuracy using proximity as a cue. Moreover, for both species, grouping by orientation similarity produced a lower level of performance than grouping by proximity. Differences emerged with respect to the use of shape similarity as a cue. In humans, grouping by shape similarity also proved less effective than grouping by proximity but the same was not observed in capuchins. These results suggest that there may be subtle differences between humans and capuchin monkeys in the weighting assigned to different grouping cues that may affect the way in which they combine local features into global shapes. Copyright 2009 APA, all rights reserved.

  12. Histological features of layers and sublayers in cortical visual areas V1 and V2 of chimpanzees, macaque monkeys, and humans

    Directory of Open Access Journals (Sweden)

    Balaram P

    2014-09-01

    Full Text Available Pooja Balaram, Nicole A Young, Jon H Kaas Department of Psychology, Vanderbilt University, Nashville, TN, USA Abstract: The layers and sublayers of primary visual cortex, or V1, in primates are easily distinguishable compared to those in other cortical areas, and are especially distinct in anthropoid primates – monkeys, apes, and humans – where they also vary in histological appearance. This variation in primate-specific specialization has led to a longstanding confusion over the identity of layer 4 and its proposed sublayers in V1. As the application of different histological markers relate to the issue of defining and identifying layers and sublayers, we applied four traditional and four more recent histological markers to brain sections of V1 and adjoining secondary visual cortex (V2 in macaque monkeys, chimpanzees, and humans in order to compare identifiable layers and sublayers in both cortical areas across these species. The use of Nissl, neuronal nuclear antigen (NeuN, Gallyas myelin, cytochrome oxidase (CO, acetylcholinesterase (AChE, nonphosphorylated neurofilament H (SMI-32, parvalbumin (PV, and vesicular glutamate transporter 2 (VGLUT2 preparations support the conclusion that the most popular scheme of V1 lamination, that of Brodmann, misidentifies sublayers of layer 3 (3Bβ and 3C as sublayers of layer 4 (4A and 4B, and that the specialized sublayer of layer 3 in monkeys, 3Bβ, is not present in humans. These differences in interpretation are important as they relate to the proposed functions of layer 4 in primate species, where layer 4 of V1 is a layer that receives and processes information from the visual thalamus, and layer 3 is a layer that transforms and distributes information to other cortical areas. Keywords: area 17, area 18, cortical layers, histology, immunohistochemistry

  13. Histological features of layers and sublayers in cortical visual areas V1 and V2 of chimpanzees, macaque monkeys, and humans.

    Science.gov (United States)

    Balaram, Pooja; Young, Nicole A; Kaas, Jon H

    2014-09-01

    The layers and sublayers of primary visual cortex, or V1, in primates are easily distinguishable compared to those in other cortical areas, and are especially distinct in anthropoid primates - monkeys, apes, and humans - where they also vary in histological appearance. This variation in primate-specific specialization has led to a longstanding confusion over the identity of layer 4 and its proposed sublayers in V1. As the application of different histological markers relate to the issue of defining and identifying layers and sublayers, we applied four traditional and four more recent histological markers to brain sections of V1 and adjoining secondary visual cortex (V2) in macaque monkeys, chimpanzees, and humans in order to compare identifiable layers and sublayers in both cortical areas across these species. The use of Nissl, neuronal nuclear antigen (NeuN), Gallyas myelin, cytochrome oxidase (CO), acetylcholinesterase (AChE), nonphosphorylated neurofilament H (SMI-32), parvalbumin (PV), and vesicular glutamate transporter 2 (VGLUT2) preparations support the conclusion that the most popular scheme of V1 lamination, that of Brodmann, misidentifies sublayers of layer 3 (3Bβ and 3C) as sublayers of layer 4 (4A and 4B), and that the specialized sublayer of layer 3 in monkeys, 3Bβ, is not present in humans. These differences in interpretation are important as they relate to the proposed functions of layer 4 in primate species, where layer 4 of V1 is a layer that receives and processes information from the visual thalamus, and layer 3 is a layer that transforms and distributes information to other cortical areas.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. The Mason-Pfizer monkey virus internal scaffold domain enables in vitro assembly of human immunodeficiency virus type 1 Gag

    Czech Academy of Sciences Publication Activity Database

    Sakalian, M.; Dittmer, S. S.; Gandy, A. D.; Rapp, N. D.; Zábranský, Aleš; Hunter, E.

    2002-01-01

    Roč. 76, č. 21 (2002), s. 10811-10820 ISSN 0022-538X Grant - others:NIH(US) CA-27834; NIH(US) AI-43230 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry Impact factor: 5.241, year: 2002

  17. Evaluation of the Monkey-Persimmon Environmental Education Program for Reducing Human-Wildlife Conflicts in Nagano, Japan

    Science.gov (United States)

    Sakurai, Ryo; Jacobson, Susan K.

    2011-01-01

    Co-existing with wildlife and maintaining rural livelihoods are common challenges in remote villages in Japan. The authors assess the effects of the Monkey-Persimmon Environmental Education Program developed to reduce wildlife conflicts and to revitalize a community in Nagano Prefecture. Development of a logic model helped guide interviews with…

  18. Box-Counting Method of 2D Neuronal Image: Method Modification and Quantitative Analysis Demonstrated on Images from the Monkey and Human Brain

    Directory of Open Access Journals (Sweden)

    Nemanja Rajković

    2017-01-01

    Full Text Available This study calls attention to the difference between traditional box-counting method and its modification. The appropriate scaling factor, influence on image size and resolution, and image rotation, as well as different image presentation, are showed on the sample of asymmetrical neurons from the monkey dentate nucleus. The standard BC method and its modification were evaluated on the sample of 2D neuronal images from the human neostriatum. In addition, three box dimensions (which estimate the space-filling property, the shape, complexity, and the irregularity of dendritic tree were used to evaluate differences in the morphology of type III aspiny neurons between two parts of the neostriatum.

  19. Box-Counting Method of 2D Neuronal Image: Method Modification and Quantitative Analysis Demonstrated on Images from the Monkey and Human Brain.

    Science.gov (United States)

    Rajković, Nemanja; Krstonošić, Bojana; Milošević, Nebojša

    2017-01-01

    This study calls attention to the difference between traditional box-counting method and its modification. The appropriate scaling factor, influence on image size and resolution, and image rotation, as well as different image presentation, are showed on the sample of asymmetrical neurons from the monkey dentate nucleus. The standard BC method and its modification were evaluated on the sample of 2D neuronal images from the human neostriatum. In addition, three box dimensions (which estimate the space-filling property, the shape, complexity, and the irregularity of dendritic tree) were used to evaluate differences in the morphology of type III aspiny neurons between two parts of the neostriatum.

  20. The virus and the vaccine: the true story of a cancer-causing monkey virus, contaminated polio vaccine, and the millions of Americans exposed

    National Research Council Canada - National Science Library

    Bookchin, Debbie; Schumacher, Jim

    2004-01-01

    .... But now SV40 in showing up in human cancers, and prominent researchers are demanding a serious public health response to this forgotten polio vaccine contaminant. A gripping medical detective story, The Virus and the Vaccine raises major questions about vaccine policy.

  1. Formal monkey linguistics : The debate

    NARCIS (Netherlands)

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

    2016-01-01

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

  2. Inhibition of microtubules and dynein rescues human immunodeficiency virus type 1 from owl monkey TRIMCyp-mediated restriction in a cellular context-specific fashion.

    Science.gov (United States)

    Pawlica, Paulina; Dufour, Caroline; Berthoux, Lionel

    2015-04-01

    IFN-induced restriction factors can significantly affect the replicative capacity of retroviruses in mammals. TRIM5α (tripartite motif protein 5, isoform α) is a restriction factor that acts at early stages of the virus life cycle by intercepting and destabilizing incoming retroviral cores. Sensitivity to TRIM5α maps to the N-terminal domain of the retroviral capsid proteins. In several New World and Old World monkey species, independent events of retrotransposon-mediated insertion of the cyclophilin A (CypA)-coding sequence in the trim5 gene have given rise to TRIMCyp (also called TRIM5-CypA), a hybrid protein that is active against some lentiviruses in a species-specific fashion. In particular, TRIMCyp from the owl monkey (omkTRIMCyp) very efficiently inhibits human immunodeficiency virus type 1 (HIV-1). Previously, we showed that disrupting the integrity of microtubules (MTs) and of cytoplasmic dynein complexes partially rescued replication of retroviruses, including HIV-1, from restriction mediated by TRIM5α. Here, we showed that efficient restriction of HIV-1 by omkTRIMCyp was similarly dependent on the MT network and on dynein complexes, but in a context-dependent fashion. When omkTRIMCyp was expressed in human HeLa cells, restriction was partially counteracted by pharmacological agents targeting MTs or by small interfering RNA-mediated inhibition of dynein. The same drugs (nocodazole and paclitaxel) also rescued HIV-1 from restriction in cat CRFK cells, although to a lesser extent. Strikingly, neither nocodazole, paclitaxel nor depletion of the dynein heavy chain had a significant effect on the restriction of HIV-1 in an owl monkey cell line. These results suggested the existence of cell-specific functional interactions between MTs/dynein and TRIMCyp. © 2015 The Authors.

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

    Directory of Open Access Journals (Sweden)

    Lucie Etienne

    2015-09-01

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

  4. What meaning means for same and different: Analogical reasoning in humans (Homo sapiens), chimpanzees (Pan troglodytes), and rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Flemming, Timothy M; Beran, Michael J; Thompson, Roger K R; Kleider, Heather M; Washburn, David A

    2008-05-01

    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. PsycINFO Database Record (c) 2008 APA, all rights reserved.

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

    Directory of Open Access Journals (Sweden)

    John K Thuita

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

  6. Intracellular free calcium concentration and calcium transport in human erythrocytes of lead-exposed workers

    International Nuclear Information System (INIS)

    Quintanar-Escorza, M.A.; Gonzalez-Martinez, M.T.; Navarro, L.; Maldonado, M.; Arevalo, B.; Calderon-Salinas, J.V.

    2007-01-01

    Erythrocytes are the route of lead distribution to organs and tissues. The effect of lead on calcium homeostasis in human erythrocytes and other excitable cells is not known. In the present work we studied the effect of lead intoxication on the uptake and efflux (measured as (Ca 2+ -Mg 2+ )-ATPase activity) of calcium were studied in erythrocytes obtained from lead-exposed workers. Blood samples were taken from 15 workers exposed to lead (blood lead concentration 74.4 ± 21.9 μg/dl) and 15 non-exposed workers (9.9 ± 2 μg/dl). In erythrocytes of lead-exposed workers, the intracellular free calcium was 79 ± 13 nM, a significantly higher concentration (ANOVA, P 2+ -Mg 2+ )-ATPase activity. Lipid peroxidation was 1.7-fold higher in erythrocytes of lead-exposed workers as compared with control. The alteration on calcium equilibrium in erythrocytes is discussed in light of the toxicological effects in lead-exposed workers

  7. Detection of genomic instability in normal human bronchial epithelial cells exposed to 238Pu

    International Nuclear Information System (INIS)

    Kennedy, C.H.; Fukushima, N.H.; Neft, R.E.; Lechner, J.F.

    1994-01-01

    Alpha particle-emitting radon daughters constitute a risk for development of lung cancer in humans. The development of this disease involves multiple genetic alterations. These changes and the time course they follow are not yet defined despite numerous in vitro endeavors to transform human lung cells with various physical or chemical agents. However, genomic instability, characterized both by structural and numerical chromosomal aberrations and by elevated rates of point mutations, is a common feature of tumor cells. Further, both types of genomic instability have been reported in the noncancerous progeny of normal murine hemopoietic cells exposed in vitro to α-particles. The purpose of this investigation was to determine if genomic instability is also a prominent feature of normal human bronchial epithelial cells exposed to α-particle irradiation from the decay of inhaled radon daughters

  8. Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628.

    Science.gov (United States)

    Varnäs, Katarina; Finnema, Sjoerd J; Stepanov, Vladimir; Takano, Akihiro; Tóth, Miklós; Svedberg, Marie; Møller Nielsen, Søren; Khanzhin, Nikolay A; Juhl, Karsten; Bang-Andersen, Benny; Halldin, Christer; Farde, Lars

    2016-08-01

    Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. A novel neurokinin 3 receptor radioligand, [(18)F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[(18)F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  9. Nuclear weapon testing and the monkey business

    International Nuclear Information System (INIS)

    Murthy, M.S.S.

    1978-01-01

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

  10. Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys.

    Science.gov (United States)

    Ashkenazi, Nurit; Rosenstock, Moti; Hallak, Hussein; Bassan, Merav; Rasamoelisolo, Michele; Leuschner, Jost; Shinar, Doron

    TV-1106 is a recombinant human albumin genetically fused to growth hormone which is intended to reduce the frequency of injections for GH therapy users. We report the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated subcutaneous injections of TV-1106 in Cynomolgus monkeys. Cynomolgus monkeys received four weekly subcutaneous injections of 0, 5, 10 or 20mg/kg TV-1106 and were monitored for safety signals throughout the study. Serum levels of TV-1106 and insulin-like growth factor 1 (IGF-1) were assayed. Treated animals showed no adverse effects or histopathological changes. TV-1106 serum concentrations showed sustained exposure to the drug. Exposure increased in a dose-dependent manner with peak concentrations at approximately 24h post-dosing and elimination half-lives in the range of 12 to 24h. IGF-1 serum concentrations were elevated throughout the entire study duration, indicative of the pharmacological response. There was a clear correlation between change in IGF-1 levels and dose or exposure to TV-1106. The safety, pharmacokinetic and pharmacodynamic findings support the further development of TV-1106 as a once-weekly administered treatment for patients with GHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Prediction of Deoxypodophyllotoxin Disposition in Mouse, Rat, Monkey and Dog by Physiologically-based Pharmacokinetic Model and the Extrapolation to Human

    Directory of Open Access Journals (Sweden)

    Yang Chen

    2016-12-01

    Full Text Available Deoxypodophyllotoxin (DPT is a potential anti-tumor candidate prior to its clinical phase. The aim of the study was to develop a physiologically-based pharmacokinetic (PBPK model consisting of 13 tissue compartments to predict DPT disposition in mouse, rat, monkey and dog based on in vitro and in silico inputs. Since large interspecies difference was found in unbound fraction of DPT in plasma, we assumed that Kt:pl,u (unbound tissue-to-plasma concentration ratio was identical across species. The predictions of our model were then validated by in vivo data of corresponding preclinical species, along with visual predictive checks. Reasonable matches were found between observed and predicted plasma concentrations and pharmacokinetic parameters in all four animal species. The prediction in the related seven tissues of mouse was also desirable. We also attempted to predict human pharmacokinetic profile by both the developed PBPK model and interspecies allometric scaling across mouse, rat and monkey, while dog was excluded from the scaling. The two approaches reached similar results. We hope the study will help in the efficacy and safety assessment of DPT in future clinical studies and provide a reference to the preclinical screening of similar compounds by PBPK model.

  12. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

    Science.gov (United States)

    Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

    2016-08-05

    Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

  13. Radiation-induced emesis in monkeys

    International Nuclear Information System (INIS)

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

    1980-01-01

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

  14. Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation.

    Science.gov (United States)

    Sannino, Anna; Sarti, Maurizio; Reddy, Siddharth B; Prihoda, Thomas J; Vijayalaxmi; Scarfì, Maria Rosaria

    2009-06-01

    The incidence of micronuclei was evaluated to assess the induction of an adaptive response to non-ionizing radiofrequency (RF) radiation in peripheral blood lymphocytes collected from five different human volunteers. After stimulation with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of 900 MHz RF radiation used for mobile communications (at a peak specific absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to examine the frequency of micronuclei in cytokinesis-blocked binucleated cells. Cells collected from four donors exhibited the induction of adaptive response (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had a significantly decreased incidence of micronuclei induced by the challenge dose of mitomycin C compared to those that were not pre-exposed to 900 MHz RF radiation. These preliminary results suggested that the adaptive response can be induced in cells exposed to non-ionizing radiation. A similar phenomenon has been reported in cells as well as in animals exposed to ionizing radiation in several earlier studies. However, induction of adaptive response was not observed in the remaining donor (i.e., non-responder). The incidence of micronuclei induced by the challenge dose of mitomycin C was not significantly different between the cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the overall data indicated the existence of heterogeneity in the induction of an adaptive response between individuals exposed to RF radiation and showed that the less time-consuming micronucleus assay can be used to determine whether an individual is a responder or non-responder.

  15. The distribution of chromosome aberrations among chromosomes of karyotype in exposed human lymphocyte

    International Nuclear Information System (INIS)

    Que Tran; Tien Hoang Hung

    1997-01-01

    Induced chromosome aberrations (ch. ab.) in exposed Human peripheral blood lymphocyte have been used to assay radio.bio.doses, because of their characters such as: the maintaining Go phase in cell cycle in body, the distribution of cell in blood system and the distribution of ch. ab. in exposed cells of body and among chromosomes of karyotype. The frequency of ch. ab. reflected the quantity of radiation dose, dose rate and radiation energy. The dependence between radiation dose and frequency of ch. ab. was illustrated by the mathematic equations. The distribution of induced ch. ab. among the cells exposed to uniform radiation fields was Poisson's, but the distribution of ch. ab. among chromosomes in karyotype depended on radiation field and mononucleotid sequence of DNA molecular of each chromosome. The minimum influence of mononucleotid sequence of DNA molecular in inform ch. ab. will be advantageous state for dose-assessments. The location of induced ch. ab. in exposed Human lymphocyte had been determined by karyotype analyses. The data of statistic analyse had improved that the number of ch. ab. depended on the size of chromosomes in karyotype. The equal distribution of ch. ab.among chromosomes in karyotype provided the objectiveness and the accuracy of using the chromosomal aberrant analysis technique on bio-dosimetry. (author)

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

    Science.gov (United States)

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

    2018-02-20

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

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

    Science.gov (United States)

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

    2009-04-01

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

  18. Characterisation of the appearance of radioactive metabolites in monkey and human plasma from the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635 - explanation of high signal contrast in PET and an aid to biomathematical modelling

    International Nuclear Information System (INIS)

    Osman, Safiye; Lundkvist, Camilla; Pike, Victor W.; Halldin, Christer; McCarron, Julie A.; Swahn, Carl-Gunnar; Farde, Lars; Ginovart, Nathalie; Luthra, Sajinder K.; Gunn, Roger N.; Bench, Christopher J.; Sargent, Peter A.; Grasby, Paul M.

    1998-01-01

    N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), labelled in its amido carbonyl group with 11 C (t 1/2 = 20.4 min), is a promising radioligand for the study of brain 5-HT 1A receptors with positron emission tomography (PET). Thus, in PET experiments in six cynomolgus monkeys and seven healthy male volunteers, [carbonyl- 11 C]WAY-100635 was taken up avidly by brain. Radioactivity was retained in regions rich in 5-HT 1A receptors, such as occipital cortex, temporal cortex and raphe nuclei, but cleared rapidly from cerebellum, a region almost devoid of 5-HT 1A receptors. [Carbonyl- 11 C]WAY-100635 provides about 3- and 10-fold higher signal contrast (receptor-specific to nonspecific binding) than [O-methyl- 11 C]WAY-100635 in receptor-rich areas of monkey and human brain, respectively. To elucidate the effect of label position on radioligand behaviour and to aid in the future biomathematical interpretation of the kinetics of regional cerebral radioactivity uptake in terms of receptor-binding parameters, HPLC was used to measure [carbonyl- 11 C]WAY-100635 and its radioactive metabolites in plasma at various times after intravenous injection. Radioactivity cleared rapidly from monkey and human plasma. Parent radioligand represented 19% of the radioactivity in monkey plasma at 47 min and 8% of the radioactivity in human plasma at 40 min. [Carbonyl- 11 C]desmethyl-WAY-100635 was below detectable limits in monkey plasma and at most a very minor radioactive metabolite in human plasma. [ 11 C]Cyclohexanecarboxylic acid was identified as a significant radioactive metabolite. In human plasma this maximally represented 21% of the radioactivity at 10 min after radioligand injection. All other major radioactive metabolites in monkey and human plasma were even more polar. No-carrier-added [carbonyl- 11 C]cyclohexanecarboxylic acid was prepared in the laboratory and after intravenous administration into cynomolgus monkey was

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

    Science.gov (United States)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  1. Biotransformation of a novel antimitotic agent, I-387, by mouse, rat, dog, monkey, and human liver microsomes and in vivo pharmacokinetics in mice.

    Science.gov (United States)

    Ahn, Sunjoo; Kearbey, Jeffrey D; Li, Chien-Ming; Duke, Charles B; Miller, Duane D; Dalton, James T

    2011-04-01

    3-(1H-Indol-2-yl)phenyl)(3,4,5-trimethoxyphenyl)methanone (I-387) is a novel indole compound with antitubulin action and potent antitumor activity in various preclinical models. I-387 avoids drug resistance mediated by P-glycoprotein and showed less neurotoxicity than vinca alkaloids during in vivo studies. We examined the pharmacokinetics and metabolism of I-387 in mice as a component of our preclinical development of this compound and continued interest in structure-activity relationships for antitubulin agents. After a 1 mg/kg intravenous dose, noncompartmental pharmacokinetic analysis in plasma showed that clearance (CL), volume of distribution at steady state (Vd(ss)), and terminal half-life (t(1/2)) of I-387 were 27 ml per min/kg, 5.3 l/kg, and 7 h, respectively. In the in vitro metabolic stability study, half-lives of I-387 were between 10 and 54 min by mouse, rat, dog, monkey, and human liver microsomes in the presence of NADPH, demonstrating interspecies variability. I-387 was most stable in rat liver microsomes and degraded quickly in monkey liver microsomes. Liquid chromatography-tandem mass spectrometry was used to identify phase I metabolites. Hydroxylation, reduction of a ketone group, and O-demethylation were the major metabolites formed by the liver microsomes of the five species. The carbonyl group of I-387 was reduced and identified as the most labile site in human liver microsomes. The results of these drug metabolism and pharmacokinetic studies provide the foundation for future structural modification of this pharmacophore to improve stability of drugs with potent anticancer effects in cancer patients.

  2. Genome Editing of Monkey.

    Science.gov (United States)

    Liu, Zhen; Cai, Yijun; Sun, Qiang

    2017-01-01

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

  3. Improved numerical modelling of heat transfer in human tissue exposed to RF

    International Nuclear Information System (INIS)

    Prishvin, Mikheil; Zaridze, Revaz; Bit-Babik, Georgi; Faraone, Antonio

    2010-01-01

    Full text: A novel numerical model to simulate thermal response of human body tissues exposed to RF energy is presented in this article. It is based on a new algorithm for the construction of a realistic blood vessel network, a new model of blood flow velocity distribution and an approach to solve the bio-heat equation in human tissue with variable and initially unknown blood temperature distribution. The algorithm generates a discrete 3D representation of both arterial and venous vascular networks and a continuous blood velocity vector field for arbitrary enclosed geome tries required to represent the complex anatomy of human body and blood flow. The results obtained in this article by applying the developed method to realistic exposure con ditions demonstrates relative difference in thermal response of the exposed tissue compared to results obtained by conventional bio-heat equation with constant blood perfusion and temperature. The developed technique may provide more accurate and realistic modelling in thermal dosimetry studies of human body RF exposure.

  4. ''Normal'' tissues from humans exposed to radium contain an alteration in the c-mos locus

    International Nuclear Information System (INIS)

    Huberman, E.; Schlenker, R.A.; Hardwick, J.P.

    1989-01-01

    The structures of a number of human proto-oncogenes from persons with internal systemic exposure to radium were analyzed by restriction enzyme digestion and southern blotting of their DNA. Two extra c-mos Eco R1 restriction-fragment-length bands of 5.0 kb and 5.5 kb were found in tissue DNA from six of seven individuals. The extra c-mos bands were detected in DNA from many, but not all, of the tissues of the individuals exposed to radium. Our results suggest that the c-mos restriction-fragment-length alterations (RFLA) found in individuals exposed to radium were induced rather than inherited, are epigenetic in origin, and most likely result from changes in the methylation of bases surrounding the single exon of the c-mos proto-oncogene. 7 refs., 3 figs., 2 tabs

  5. EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

    DEFF Research Database (Denmark)

    Axelstad Petersen, Marta; Hass, Ulla; Scholze, M.

    2018-01-01

    and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes...... of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant......Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we...

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

    Directory of Open Access Journals (Sweden)

    Mark ePearson

    2015-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  8. Basic math in monkeys and college students.

    Science.gov (United States)

    Cantlon, Jessica F; Brannon, Elizabeth M

    2007-12-01

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

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

    International Nuclear Information System (INIS)

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

    1977-01-01

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

  10. Investigation of micronuclei induction in human peripheral blood lymphocytes exposed in vitro to EMF RF

    International Nuclear Information System (INIS)

    Kolomiets, Irina A.; Triapitsina, Galina A.; Polevik, Nikolai D.; Pryakhin, Evgeny A.

    2008-01-01

    Full text: The widespread application of cellular phones is of great concern in view possible consequences for human health. The aim of this study is to assess the capability of electromagnetic fields (EMF) RF with frequency 925 MHz and modulation 217 Hz to induce genotoxic effects as evaluated by the in vitro micronucleus assay on peripheral blood lymphocytes. The flasks of peripheral blood samples collected from healthy volunteers (5 men and 5 women) were placed just on the oscillator of emitting antenna. The signals were produced by the laboratory research plant and were evaluated at four specific absorption rates (SARs) - 0; 0.29; 1.2; 8.1 W/kg. SARs were determined by the calorimetric method. Phytohaemagglutinin stimulated lymphocytes were exposed three times for 10 minutes in the G o (the first 30 minutes after the beginning of cultivation), S (24 hours later), G 2 -M (after 48 hours from the beginning of cultivation) stages of the cell cycle. 72-hours cultures of lymphocytes were examined to determine the extent of micronuclei. The Mann-Whitney U-test was used to evaluate the significance for comparison. The data indicated a significant increase of micronuclei in human lymphocytes exposed to EMF RF (6.5 ± 0.51 0/00; 7.1 ± 0.66 0/00; 7.0 ± 0.50 0/00) in comparison with sham-exposed lymphocytes (3.0 ± 0.60 0/00). There was not revealed a dose-dependent increase of micronuclei in human lymphocytes. It was suggested that the increase of micronuclei in lymphocytes is explicated by a particularity of EMF RF just near the oscillator of emitting antenna. (author)

  11. Review of epidemiological studies of human populations exposed to ionizing radiation

    International Nuclear Information System (INIS)

    Rao, B.S.

    2002-01-01

    Epidemiological studies undertaken in many radiation exposed cohorts have played an important role in the quantification of radiation risk. Follow up of nearly 100,000 A-bomb survivors by the Radiation Effects Research Foundation (RERF), constitutes the most comprehensive human epidemiological study. The study population covered both sexes, different age groups and dose ranges from a few mSv to 2-3 Sv. Among nearly 90,000 cohorts, as on 1990, 54% are alive. Among these, 35,000 are those exposed as children at the age<20 years. Nearly 20 % of the mortalities (8,040) were due to cancer. It was estimated from the analysis of these data that among the cancers observed in LSS cohorts, 425±45 cases (335 solid cancers+90 leukaemias) were attributable to radiation exposure. Assuming a value of two for DDREF, ICRP 60, 1991 estimated a cancer risk of 5% per Sv for low dose and low dose rate exposure conditions. There have been a number of efforts to study the human populations exposed to low level radiations. Epidemiological studies on nuclear workers from USA, UK and Canada constituting 95,673 workers spanning 2,124,526 person years was reported by Cardis et al. (1995). Total number of deaths were 15,825, of which 3,976 were cancer mortalities. The excess relative risk for all cancers excluding leukaemia is -0.07 per Sv (-0.4- +0.3) and for leukaemia (excluding CLL) is 2.18 (0.1-5.7). Epidemiological studies in high background radiation areas (HBRA) of Yangjiang, China and coastal Kerala showed no detectable increase in the incidence of cancers or of any genetic disorders. Epidemiological studies in human populations exposed to elevated background radiation for several generations did not show any increase in the genetic disorders. Recent information on the background incidence of monogenic disorders in human populations and the recoverability factor of induced genetic changes suggests a risk much lower than the earlier ICRP estimates. Many other epidemiological studies of

  12. Sensible biological models to be exposed to VDT (Video Display Terminal) radiations in human male reproduction

    International Nuclear Information System (INIS)

    Tritto, J.; North, M.-O.; Laverdure, A.M.; Surbeck, J.

    1999-01-01

    Temperature and environmental effects, particularly endocrine disrupters and EMF radiations, are actively investigated in human and non-human reproduction experimental models. Sensitivity and specificity of the different cell types of the testes seminiferous tubules in animals and in human are evaluated, showing a specific responsiveness of spermatogonia (SPG) and resting pachytene spermatocytes (SPC). At 32 o C the 24 h short-term cultures of biopsies of normal human testis show an expected low occurrence of apoptotic SPG (1 %) that increases to 3,4 % in peer samples exposed to VDT for the same period, with the appearance of apoptotic SPC (4,6 %). In samples from a thermically-impaired testis of the same subject the apoptotic occurrence of SPG is 2,6 % with 15,4 % for SPC after 24 h cultures. After 24 h exposure to VDT the apoptotic score is 7,6 % for SPG and 18,5 % for SPC in thermically impaired peer samples. With EMF-bioshields the apoptotic score for SPG is 0,8 % in normal 2,2 % for SPG and 13,8 % for SPC in T-impaired peer-samples. NMRS of the cultures fluids show a proportional production of lactate, corresponding to the different degrees of histopathological impairment of the samples. IVOS (Integrated Visual Optic System) analysis of sperm samples from thermically-impaired, not-repaired and repaired testes exposed to VDT shows sensible variations on straightness (STR), linearity (LIN) and lateral head displacement (LHD) parameters. To evaluate the thermic and non-thermic potential bioeffects of VDT on human spermatogenesis the specificity, the sensitivity and the reproducibility of the biological models on one side and the specificity of the methodologies on the other side must be provided. (author)

  13. Toward a Method for Exposing and Elucidating Ethical Issues with Human Cognitive Enhancement Technologies.

    Science.gov (United States)

    Hofmann, Bjørn

    2017-04-01

    To develop a method for exposing and elucidating ethical issues with human cognitive enhancement (HCE). The intended use of the method is to support and facilitate open and transparent deliberation and decision making with respect to this emerging technology with great potential formative implications for individuals and society. Literature search to identify relevant approaches. Conventional content analysis of the identified papers and methods in order to assess their suitability for assessing HCE according to four selection criteria. Method development. Amendment after pilot testing on smart-glasses. Based on three existing approaches in health technology assessment a method for exposing and elucidating ethical issues in the assessment of HCE technologies was developed. Based on a pilot test for smart-glasses, the method was amended. The method consists of six steps and a guiding list of 43 questions. A method for exposing and elucidating ethical issues in the assessment of HCE was developed. The method provides the ground work for context specific ethical assessment and analysis. Widespread use, amendments, and further developments of the method are encouraged.

  14. Guanfu base A, an antiarrhythmic alkaloid of Aconitum coreanum, Is a CYP2D6 inhibitor of human, monkey, and dog isoforms.

    Science.gov (United States)

    Sun, Jianguo; Peng, Ying; Wu, Hui; Zhang, Xueyuan; Zhong, Yunxi; Xiao, Yanan; Zhang, Fengyi; Qi, Huanhuan; Shang, Lili; Zhu, Jianping; Sun, Yue; Liu, Ke; Liu, Jinghan; A, Jiye; Ho, Rodney J Y; Wang, Guangji

    2015-05-01

    Guanfu base A (GFA) is a novel heterocyclic antiarrhythmic drug isolated from Aconitum coreanum (Lèvl.) rapaics and is currently in a phase IV clinical trial in China. However, no study has investigated the influence of GFA on cytochrome P450 (P450) drug metabolism. We characterized the potency and specificity of GFA CYP2D inhibition based on dextromethorphan O-demethylation, a CYP2D6 probe substrate of activity in human, mouse, rat, dog, and monkey liver microsomes. In addition, (+)-bufuralol 1'-hydroxylation was used as a CYP2D6 probe for the recombinant form (rCYP2D6), 2D1 (rCYP2D1), and 2D2 (rCYP2D2) activities. Results show that GFA is a potent noncompetitive inhibitor of CYP2D6, with inhibition constant Ki = 1.20 ± 0.33 μM in human liver microsomes (HLMs) and Ki = 0.37 ± 0.16 μM for the human recombinant form (rCYP2D6). GFA is also a potent competitive inhibitor of CYP2D in monkey (Ki = 0.38 ± 0.12 μM) and dog (Ki = 2.4 ± 1.3 μM) microsomes. However, GFA has no inhibitory activity on mouse or rat CYP2Ds. GFA did not exhibit any inhibition activity on human recombinant CYP1A2, 2A6, 2C8, 2C19, 3A4, or 3A5, but showed slight inhibition of 2B6 and 2E1. Preincubation of HLMs and rCYP2D6 resulted in the inactivation of the enzyme, which was attenuated by GFA or quinidine. Beagle dogs treated intravenously with dextromethorphan (2 mg/ml) after pretreatment with GFA injection showed reduced CYP2D metabolic activity, with the Cmax of dextrorphan being one-third that of the saline-treated group and area under the plasma concentration-time curve half that of the saline-treated group. This study suggests that GFA is a specific CYP2D6 inhibitor that might play a role in CYP2D6 medicated drug-drug interaction. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Distribution of seratonin-1A receptors in the monkey and the postmortem human hippocampal region. A quantitative autoradiographic study using the selective agonist (3H)8-PH-DPAT

    International Nuclear Information System (INIS)

    Koehler, Christer; Radesaeter, A.C.; Lang, Walter; Chan-Palay, Victoria

    1986-01-01

    Serotonin-1A receptors were visualized and their anatomical distribution mapped within the monkey and the human hippocampus by using in vitro receptor autoradiography of the selective agonist ( 3 H)8-OH-N, N-dipropyl-2-aminotetralin (( 3 H)8-OH-DPAT). The results show high densities of serotonin-1A receptors hetergeneously distributed in different subfields and layers of the monkey and the human hippocampal region. High densities are found in the molecular layer of area dentata, all layers of regio superior and the subiculum, parasubiculum, and layers 2, and 4 through 6 of the entorhinal area. In the human hippocampus, a distinct band of ( 3 H)8-OH-DPAT binding sites is present in the subgranular zone of the area dentata. The similar anatomical distribution of ( 3 H)8-OH-DPAT binding sites in the monkey and the human hippocampal region suggests that the serotonin-1A receptor is phylogenetically well preserved and indicates that this receptor may mediate action(s) of serotonin in the primate, including the human hippocampal region. (author)

  16. Whole-body biodistribution and radiation dosimetry in monkeys and humans of the phosphodiesterase 4 radioligand [11C](R)-rolipram: comparison of two-dimensional planar, bisected and quadrisected image analyses

    International Nuclear Information System (INIS)

    Sprague, David R.; Fujita, Masahiro; Ryu, Yong Hoon; Liow, Jeih-San; Pike, Victor W.; Innis, Robert B.

    2008-01-01

    Introduction: [ 11 C](R)-Rolipram is a selective radioligand for positron emission tomography (PET) imaging of phosphodiesterase 4, an enzyme that metabolizes 3',5'-cyclic adenosine monophosphate. The aim of this study was to estimate the human radiation absorbed dose of the radioligand based on its biodistribution in both monkeys and humans. Methods: Whole-body PET images were acquired for 2 h after injecting [ 11 C](R)-rolipram in eight healthy humans and three monkeys. The simple method of using a single two-dimensional (2D) planar image was compared to more time-consuming methods that used two (bisected) or four (quadrisected) tomographic images in the anteroposterior direction. Results: Effective dose was 4.8 μGy/MBq based on 2D planar images. The effective dose was only slightly lower by 1% and 5% using the bisected and quadrisected images, respectively. Nevertheless, the two tomographic methods may have more accurately estimated the exposure of some organs (e.g., kidneys) that are asymmetrically located in the body or have radioactivity that appears to overlap on 2D planar images. Monkeys had a different biodistribution pattern compared to humans (e.g., greater urinary excretion) such that their data overestimated the effective dose in humans by 40%. Conclusions: The effective dose of [ 11 C](R)-rolipram was modest and comparable to that of other 11 C-labeled radioligands. The simple and far less time-consuming 2D planar method provided accurate and somewhat more conservative estimates of effective dose than the two tomographic methods. Although monkeys are commonly used to estimate human radiation exposures, their data gave a considerable overestimation for this radioligand

  17. Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human immunostimulatory sequences and the GM-CSF gene increases immunogenicity and protection from virus challenge in Aotus monkeys

    International Nuclear Information System (INIS)

    Raviprakash, Kanakatte; Ewing, Dan; Simmons, Monika; Porter, Kevin R.; Jones, Trevor R.; Hayes, Curtis G.; Stout, Richard; Murphy, Gerald S.

    2003-01-01

    A dengue-1 DNA vaccine containing sequences encoding premembrane and envelope proteins (DIME) was previously shown to elicit virus neutralizing antibodies in rhesus and Aotus monkeys, and the primates were partially protected from viremia upon challenge. To increase the neutralizing antibody levels and subsequent protection from virus challenge, four strategies were evaluated: (a) coimmunization with a plasmid expressing Aotus GM-CSF gene; (b) coimmunization with a plasmid containing human immunostimulatory sequences (ISS); (c) coimmunization with both the GM-CSF gene and ISS; and (d) delivery of vaccine using the needle-free Biojector system. Vaccination with the mixed formulation containing DIME, GM-CSF gene, and ISS, by either needle injection or Biojector, led to neutralizing antibody titers that were stable for up to 6 months after vaccination. Furthermore, 6 of 7 monkeys (85%), and 7 of 8 monkeys (87%) receiving this formulation were completely protected from viremia when challenged 1 and 6 months after vaccination, respectively. This is a significant improvement compared to our previous study in which one of three monkeys (33%) receiving just the DIME vaccine was completely protected from viremia at 6 months after immunization

  18. Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.

    Directory of Open Access Journals (Sweden)

    Cleo Robinson

    Full Text Available Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44-2.29, p = 0.99. Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61-1.67, p = 0.97. We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.

  19. Alterations in physical state of silver nanoparticles exposed to synthetic human stomach fluid

    International Nuclear Information System (INIS)

    Rogers, Kim R.; Bradham, Karen; Tolaymat, Thabet; Thomas, David J.; Hartmann, Thomas; Ma, Longzhou; Williams, Alan

    2012-01-01

    The bioavailability of ingested silver nanoparticles (AgNPs) depends in large part on initial particle size, shape and surface coating, properties which will influence aggregation, solubility and chemical composition during transit of the gastrointestinal tract. Citrate-stabilized AgNPs were exposed to synthetic human stomach fluid (SSF) (pH 1.5) and changes in size, shape, zeta potential, hydrodynamic diameter and chemical composition were determined during a 1 h exposure period using Surface Plasmon Resonance (SPR), High Resolution Transmission Electron Microscopy/Energy Dispersive X-ray Spectroscopy (TEM/EDS), Dynamic Light Scattering (DLS) and X-ray Powder Diffraction (XRD) combined with Rietveld analysis. Exposure of AgNPs to SSF produced a rapid decrease in the SPR peak at 414 nm and the appearance of a broad absorbance peak in the near infrared (NIR) spectral region. During exposure to SSF, changes in zeta potential, aggregation and morphology of the particles were also observed as well as production of silver chloride which appeared physically associated with particle aggregates. - Highlights: ► Citrate-stabilized AgNPs were exposed to synthetic human stomach fluid (pH 1.5). ► Particle changes in chemical composition, zeta potential, aggregation and morphology were observed. ► Silver chloride appeared to be physically associated with the particle aggregates.

  20. Alterations in physical state of silver nanoparticles exposed to synthetic human stomach fluid

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Kim R., E-mail: rogers.kim@epa.gov [U.S. Environmental Protection Agency, Las Vegas, NV (United States); Bradham, Karen [U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Tolaymat, Thabet [U.S. Environmental Protection Agency, Cincinnati, OH (United States); Thomas, David J. [U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Hartmann, Thomas; Ma, Longzhou [University of Nevada, Harry Reid Center for Environmental Studies, Las Vegas, NV (United States); Williams, Alan [U.S. Environmental Protection Agency, Las Vegas, NV (United States)

    2012-03-15

    The bioavailability of ingested silver nanoparticles (AgNPs) depends in large part on initial particle size, shape and surface coating, properties which will influence aggregation, solubility and chemical composition during transit of the gastrointestinal tract. Citrate-stabilized AgNPs were exposed to synthetic human stomach fluid (SSF) (pH 1.5) and changes in size, shape, zeta potential, hydrodynamic diameter and chemical composition were determined during a 1 h exposure period using Surface Plasmon Resonance (SPR), High Resolution Transmission Electron Microscopy/Energy Dispersive X-ray Spectroscopy (TEM/EDS), Dynamic Light Scattering (DLS) and X-ray Powder Diffraction (XRD) combined with Rietveld analysis. Exposure of AgNPs to SSF produced a rapid decrease in the SPR peak at 414 nm and the appearance of a broad absorbance peak in the near infrared (NIR) spectral region. During exposure to SSF, changes in zeta potential, aggregation and morphology of the particles were also observed as well as production of silver chloride which appeared physically associated with particle aggregates. - Highlights: Black-Right-Pointing-Pointer Citrate-stabilized AgNPs were exposed to synthetic human stomach fluid (pH 1.5). Black-Right-Pointing-Pointer Particle changes in chemical composition, zeta potential, aggregation and morphology were observed. Black-Right-Pointing-Pointer Silver chloride appeared to be physically associated with the particle aggregates.

  1. Molecular Characterization of TP53 Gene in Human Populations Exposed to Low-Dose Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Igor Brasil-Costa

    2013-01-01

    Full Text Available Ionizing radiation, such as that emitted by uranium, may cause mutations and consequently lead to neoplasia in human cells. The TP53 gene acts to maintain genomic integrity and constitutes an important biomarker of susceptibility. The present study investigated the main alterations observed in exons 4, 5, 6, 7, and 8 of the TP53 gene and adjacent introns in Amazonian populations exposed to radioactivity. Samples were collected from 163 individuals. Occurrence of the following alterations was observed: (i a missense exchange in exon 4 (Arg72Pro; (ii 2 synonymous exchanges, 1 in exon 5 (His179His, and another in exon 6 (Arg213Arg; (iii 4 intronic exchanges, 3 in intron 7 (C → T at position 13.436; C → T at position 13.491; T → G at position 13.511 and 1 in intron 8 (T → G at position 13.958. Alteration of codon 72 was found to be an important risk factor for cancer development (P=0.024; OR=6.48; CI: 1.29–32.64 when adjusted for age and smoking. Thus, TP53 gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation.

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

    Science.gov (United States)

    Lieberman, Philip

    2017-07-01

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

  3. TRX-ASK1-JNK signaling regulation of cell density-dependent cytotoxicity in cigarette smoke-exposed human bronchial epithelial cells.

    Science.gov (United States)

    Lee, Yong Chan; Chuang, Chun-Yu; Lee, Pak-Kei; Lee, Jin-Soo; Harper, Richart W; Buckpitt, Alan B; Wu, Reen; Oslund, Karen

    2008-05-01

    Cigarette smoke is a major environmental air pollutant that injures airway epithelium and incites subsequent diseases including chronic obstructive pulmonary disease. The lesion that smoke induces in airway epithelium is still incompletely understood. Using a LIVE/DEAD cytotoxicity assay, we observed that subconfluent cultures of bronchial epithelial cells derived from both human and monkey airway tissues and an immortalized normal human bronchial epithelial cell line (HBE1) were more susceptible to injury by cigarette smoke extract (CSE) and by direct cigarette smoke exposure than cells in confluent cultures. Scraping confluent cultures also caused an enhanced cell injury predominately in the leading edge of the scraped confluent cultures by CSE. Cellular ATP levels in both subconfluent and confluent cultures were drastically reduced after CSE exposure. In contrast, GSH levels were significantly reduced only in subconfluent cultures exposed to smoke and not in confluent cultures. Western blot analysis demonstrated ERK activation in both confluent and subconfluent cultures after CSE. However, activation of apoptosis signal-regulating kinase 1 (ASK1), JNK, and p38 were demonstrated only in subconfluent cultures and not in confluent cultures after CSE. Using short interfering RNA (siRNA) to JNK1 and JNK2 and a JNK inhibitor, we attenuated CSE-mediated cell death in subconfluent cultures but not with an inhibitor of the p38 pathway. Using the tetracycline (Tet)-on inducible approach, overexpression of thioredoxin (TRX) attenuated CSE-mediated cell death and JNK activation in subconfluent cultures. These results suggest that the TRX-ASK1-JNK pathway may play a critical role in mediating cell density-dependent CSE cytotoxicity.

  4. Global gene expression profiling in human lung cells exposed to cobalt

    Energy Technology Data Exchange (ETDEWEB)

    Malard, V.; Berenguer, F.; Prat, O.; Ruat, S.; Steinmetz, G.; Quemeneur, E. [CEA VALRHO, Serv Biochim and Toxicol Nucl, DSV, iBEB, F-30207 Bagnols Sur Ceze (France)

    2007-06-06

    It has been estimated that more than 1 million workers in the United States are exposed to cobalt. Occupational exposure to {sup 59}Co occurs mainly via inhalation and leads to various lung diseases. Cobalt is classified by the IARC as a possible human carcinogen (group 2B). Although there is evidence for in vivo and in vitro toxicity, the mechanisms of cobalt-induced lung toxicity are not fully known. The purpose of this work was to identify potential signatures of acute cobalt exposure using a toxico-genomic approach. Data analysis focused on some cellular processes and protein targets that are thought to be relevant for carcinogenesis, transport and bio-marker research. Results: A time course transcriptome analysis was performed on A549 human pulmonary cells, leading to the identification of 85 genes which are repressed or induced in response to soluble 59 Co. A group of 29 of these genes, representing the main biological functions, was assessed by quantitative RT-PCR. The expression profiles of six of them were then tested by quantitative RT-PCR in a time-dependent manner and three modulations were confirmed by Western blotting. The 85 modulated genes include potential cobalt carriers (FBXL2, ZNT1, SLC12A5), tumor suppressors or transcription factors (MAZ, DLG1, MYC, AXL) and genes linked to the stress response (UBC, HSPCB, BN1P3L). We also identified nine genes coding for secreted proteins as candidates for bio-marker research. Of those, T1MP2 was found to be down-regulated and this modulation was confirmed, in a dose-dependent manner, at protein level in the supernatant of exposed cells. Conclusion: Most of these genes have never been described as related to cobalt stress and provide original hypotheses for further study of the effects of this metal ion on human lung epithelial cells. A putative bio-marker of cobalt toxicity was identified. (authors)

  5. Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects

    International Nuclear Information System (INIS)

    McHale, Cliona M.; Zhang, Luoping; Hubbard, Alan E.; Zhao, Xin; Baccarelli, Andrea; Pesatori, Angela C.; Smith, Martyn T.; Landi, Maria Teresa

    2007-01-01

    Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen and exerts toxic effects on the skin (chloracne). Effects on reproductive, immunological, and endocrine systems have also been observed in animal models. TCDD acts through the aryl hydrocarbon receptor (AhR) pathway influencing largely unknown gene networks. An industrial accident in Seveso, Italy in 1976 exposed thousands of people to substantial quantities of TCDD. Twenty years after the exposure, this study examines global gene expression in the mononuclear cells of 26 Seveso female never smokers, with similar age, alcohol consumption, use of medications, and background plasma levels of 22 dioxin congeners unrelated to the Seveso accident. Plasma dioxin levels were still elevated in the exposed subjects. We performed analyses in two different comparison groups. The first included high-exposed study subjects compared with individuals with background TCDD levels (average plasma levels 99.4 and 6.7 ppt, respectively); the second compared subjects who developed chloracne after the accident, and those who did not develop this disease. Overall, we observed a modest alteration of gene expression based on dioxin levels or on chloracne status. In the comparison between high levels and background levels of TCDD, four histone genes were up-regulated and modified expression of HIST1H3H was confirmed by real-time PCR. In the comparison between chloracne case-control subjects, five hemoglobin genes were up-regulated. Pathway analysis revealed two major networks for each comparison, involving cell proliferation, apoptosis, immunological and hematological disease, and other pathways. Further examination of the role of these genes in dioxin induced-toxicity is warranted

  6. Monkey cortex through fMRI glasses.

    Science.gov (United States)

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

    2014-08-06

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

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

    Directory of Open Access Journals (Sweden)

    James N Mubiru

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

  8. Collagen cross-linking in sun-exposed and unexposed sites of aged human skin

    Science.gov (United States)

    Yamauchi, M.; Prisayanh, P.; Haque, Z.; Woodley, D. T.

    1991-01-01

    A recently described nonreducible, acid-heat stable compound, histidinohydroxylysinonorleucine (HHL), is a collagen cross-link isolated from mature skin tissue. Its abundance is related to chronologic aging of skin. The present communication describes the quantity of HHL from aged human skin of the same individuals in sun-exposed (wrist) and unexposed (buttock) sites. Punch biopsies were obtained from these sites from nine people of age 60 or older. HHL contents (moles/mole of collagen) at these sites were for wrist 0.13 +/- 0.07 and for buttock 0.69 +/- 0.17 (mean +/- SD, p less than 0.001). In addition, it was found that acute irradiation of the cross-linked peptides with UVA (up to 250 J/cm2) and UVB (up to 1 J/cm2) had no effect on HHL structure. The same treatment significantly degraded another nonreducible, stable collagen cross-link, pyridinoline. The results suggest that chronic sunlight exposure may be associated with an impediment to normal maturation of human dermal collagen resulting in tenuous amount of HHL. Thus, the process of photoaging in dermal collagen is different from that of chronologic aging in human skin.

  9. Comparison of radiological changes in humans exposed to radium and in beagle dogs injected with radium

    International Nuclear Information System (INIS)

    Morgan, J.P.; Kirsh, J.E.; Pool, R.R.

    1982-01-01

    Data from MIT and New Jersey studies were combined with data from the Center for Human Radiobiology, Argonne National Laboratory, to create a material of 2259 persons occupationaly exposed to radium. The population studied consisted of radium-dial painters, radium chemists, and persons who had received radium in past years in attempts to treat various medical conditions. Within a colony of beagle dogs at the LEHR, UCD, which received eight semi-monthly injections of 226 Ra were 28 dogs that received a dosage of 80 to 130 times maximum permissible skeletal burden for man (0.1 μCi 226 Ra). The intravenous injections of 226 Ra began at 435 days of age

  10. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise

    DEFF Research Database (Denmark)

    Avnstorp, Magnus B; Rasmussen, Peter; Brassard, Patrice

    2015-01-01

    both circumstances. No cerebral net exchange of Na(+) or K(+) was evident. Likewise, no significant net-exchange of water over the brain was demonstrated and the arterial and jugular venous hemoglobin concentrations were similar. CONCLUSION: Challenging exercise in hypoxia for 30 min affected muscle......Avnstorp, Magnus B., Peter Rasmussen, Patrice Brassard, Thomas Seifert, Morten Overgaard, Peter Krustrup, Niels H. Secher, and Nikolai B. Nordsborg. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise. High Alt Med Biol 16:000-000, 2015.-Background...... intense exercise is carried out in hypoxia and monitored the influence of muscle metabolism for changes in arterial variables. METHODS: On two separate days, in random order, 30 min cycling exercise was performed in either hypoxia (10% O2) or normoxia at an intensity that was exhaustive in the hypoxic...

  11. Caregiver experience in preventive treatment for children exposed to Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Mariana Ramos da Silva

    2014-12-01

    Full Text Available This study aimed to understand the experience of caregivers of children vertically exposed to the Human Immunodeficiency Virus. It used Symbolic Interactionism as a theoretical framework. It is a qualitative research with data collection carried out in a reference clinic in a municipality in the state of São Paulo, from November 2012 to August 2013 through semi-structured interviews with 12 mothers and a grandmother. Data were analyzed using the Content Analysis method. The caregivers administered antiretroviral to child to prevent virus infection and perceived good acceptance of medication. The child was considered healthy and waiting for the test results generated suffering. Family support and public health services were highlighted as an aid to go through this route pervaded by prejudice, lack of direction, fear and inability to breastfeed. It was noted that the public health service in the city studied tried to follow the protocol requirements established, however, improvements in the quality of counselling is needed.

  12. The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

    International Nuclear Information System (INIS)

    Zhang, Li; Gong, Aimin; Ji, Jun; Wu, Yuanyuan; Zhu, Xiaoyu; Lv, Suqing; Lv, Hongzhu; Sun, Xizhuo

    2007-01-01

    This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells. The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions in vitro. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect. Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration. Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner

  13. DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

    Science.gov (United States)

    Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  15. Linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: A comparison between human, cynomolgus monkey and hFcRn Tg32 transgenic mouse using a population-modeling approach.

    Science.gov (United States)

    Betts, Alison; Keunecke, Anne; van Steeg, Tamara J; van der Graaf, Piet H; Avery, Lindsay B; Jones, Hannah; Berkhout, Jan

    2018-04-10

    The linear pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) can be considered a class property with values that are similar to endogenous IgG. Knowledge of these parameters across species could be used to avoid unnecessary in vivo PK studies and to enable early PK predictions and pharmacokinetic/pharmacodynamic (PK/PD) simulations. In this work, population-pharmacokinetic (popPK) modeling was used to determine a single set of 'typical' popPK parameters describing the linear PK of mAbs in human, cynomolgus monkey and transgenic mice expressing the human neonatal Fc receptor (hFcRn Tg32), using a rich dataset of 27 mAbs. Non-linear PK was excluded from the datasets and a 2-compartment model was applied to describe mAb disposition. Typical human popPK estimates compared well with data from comparator mAbs with linear PK in the clinic. Outliers with higher than typical clearance were found to have non-specific interactions in an affinity-capture self-interaction nanoparticle spectroscopy assay, offering a potential tool to screen out these mAbs at an early stage. Translational strategies were investigated for prediction of human linear PK of mAbs, including use of typical human popPK parameters and allometric exponents from cynomolgus monkey and Tg32 mouse. Each method gave good prediction of human PK with parameters predicted within 2-fold. These strategies offer alternative options to the use of cynomolgus monkeys for human PK predictions of linear mAbs, based on in silico methods (typical human popPK parameters) or using a rodent species (Tg32 mouse), and call into question the value of completing extensive in vivo preclinical PK to inform linear mAb PK.

  16. EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

    Directory of Open Access Journals (Sweden)

    M Axelstad

    2018-01-01

    Full Text Available Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16–20 throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10  months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

  17. Default Mode of Brain Function in Monkeys

    Science.gov (United States)

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

    2013-01-01

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

  18. Mechanisms of mutagenesis in human cells exposed to 55 MeV protons

    Science.gov (United States)

    Gauny, S.; Wiese, C.; Kronenberg, A.

    2001-01-01

    Protons represent the major type of charged particle radiation in spaceflight environments. The purpose of this study was to assess mutations arising in human lymphoid cells exposed to protons. Mutations were quantitated at the thymidine kinase (TK1) locus in cell lines derived from the same donor: TK6 cells (wt TP53) and WTK1 cells (mutant TP53). WTK1 cells were much more susceptible to mutagenesis following proton exposure than TK6 cells. Intragenic deletions were observed among early-arising TK1 mutants in TK6 cells, but not in WTK1 cells where all of the mutants arose by LOH. Deletion was the predominant mode of LOH in TK6 cells, while allelic recombination was the major mode of LOH in WTK1 cells. Deletions were of variable lengths, from <1 cM to 64 cM, while mutations that arose by allelic recombination often extended to the telomere. In summary, proton exposures elicited many types of mutations at an autosomal locus in human cells. Most involved large scale loss of genetic information, either through deletion or by recombination.

  19. Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress

    Science.gov (United States)

    Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Diamond, Michael P.; Singh, Manvinder; Hertz, Michael; Dai, Jing

    2015-01-01

    Human first-trimester trophoblast cells proliferate at low O2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-NG-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. PMID:25431453

  20. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C

    Directory of Open Access Journals (Sweden)

    Diane M. Da Silva

    2015-12-01

    Full Text Available Human papillomaviruses (HPV establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC, the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C, and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8+ T cells in vitro. Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8+ T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection. Keywords: Papillomavirus, HPV16, Langerhans cells, Immune escape

  1. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Rijkee, Laurie K; Skeate, Joseph G; Taylor, Julia R; Koopman, Maaike E; Brand, Heike E; Wong, Michael K; McKee, Greg M; Salazar, Andres M; Kast, W Martin

    2015-12-01

    Human papillomaviruses (HPV) establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC), the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C) is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C), and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8 + T cells in vitro . Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8 + T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection.

  2. Behavior of exposed human lymphocytes to a neutron beam of the Reactor TRIGA Mark III

    International Nuclear Information System (INIS)

    Carbajal R, M. I.; Arceo M, C.; Aguilar H, F.; Guerrero C, C.

    2012-10-01

    The living beings are permanently exposed to radiations of natural origin: cosmic and geologic, as well as the artificial radiations that come from sources elaborated by the man. The artificial sources have an important use in the medical area. Particularly has been increased the neutrons use due to the effectiveness that they have to damage the cells with regard to other radiation types. The biological indicator of exposition to ionizing radiation more reliable is the chromosomal aberrations study, specifically the dicentrics in human lymphocytes. This test allows, establishing the exposition dose in function of the damage quantity. The dicentrics have a behavior in function of the dose. The calibration curve that describes this behavior is specific for each type of ionizing radiation. In the year 2006 beginning was given to the expositions of human lymphocytes to a neutron beam generated in the reactor TRIGA Mark III of the Instituto Nacional de Investigaciones Nucleares (ININ) in Mexico. Up to 2008 the response dose curve comprised an interval of exposition time of up to 30 minutes. Moreover, the interval between 10 an 20 minutes is included, since was observed that this last is indispensable for the adjustment waited in a lineal model. (Author)

  3. Lead (Pb) in sheep exposed to mining pollution: implications for animal and human health.

    Science.gov (United States)

    Pareja-Carrera, Jennifer; Mateo, Rafael; Rodríguez-Estival, Jaime

    2014-10-01

    Livestock from the ancient mining area of Sierra Madrona and Alcudia Valley (Spain) is exposed to elevated levels of lead (Pb), as previous studies based on blood monitoring have revealed. Here we have studied blood, liver and muscle Pb levels in sheep in order to know if Pb exposure could represent a risk for human consumers of the meat and offal of these animals. A cross-sectional study was conducted with ≥4 years old (adults) ewes from the mining area (n=46) and a control area (n=21). Blood samples were taken before the sacrifice at the slaughterhouse, and liver and muscle samples were taken thereafter. At the same time, 2-3 year old rams (subadults, n=17) were blood sampled in the mining area. Blood, liver and muscle Pb levels were higher in the mining than in the control area. Blood Pb concentration in the mining area (n= 44, mean: 6.7μg/dl in ewes and 10.9μg/dl in rams) was above background levels (>6μg/dl) in 73.3 percent of animals. Liver Pb concentration in 68 percent of sheep from the mining area (n=32, mean: 6.16μg/g dry weight, d.w.) exceeded the minimum level associated with toxic exposure (5µg/g d.w.) and 87.5 percent of liver samples were above European Union Maximum Residue Levels (MRL) established for offal destined for human consumption (0.5µg/g w.w.~1.4µg/g d.w.). On the contrary, none of the muscle samples in ewes exceeded the EU MRL (0.1µg/g w.w.~0.34µg/g d.w.) established for meat, which may be related to the decline of blood Pb levels with age observed in the present study. These results suggest a potential health effect for sheep exposed to Pb pollution in this area and implications for food safety, but further research with lamb meat may be necessary to refine the risk assessment for human consumers. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Genetic integrity of the human Y chromosome exposed to groundwater arsenic

    Directory of Open Access Journals (Sweden)

    Ali Sher

    2010-08-01

    Full Text Available Abstract Background Arsenic is a known human carcinogen reported to cause chromosomal deletions and genetic anomalies in cultured cells. The vast human population inhabiting the Ganges delta in West Bengal, India and Bangladesh is exposed to critical levels of arsenic present in the groundwater. The genetic and physiological mechanism of arsenic toxicity in the human body is yet to be fully established. In addition, lack of animal models has made work on this line even more challenging. Methods Human male blood samples were collected with their informed consent from 5 districts in West Bengal having groundwater arsenic level more than 50 μg/L. Isolation of genomic DNA and preparation of metaphase chromosomes was done using standard protocols. End point PCR was performed for established sequence tagged sites to ascertain the status of recombination events. Single nucleotide variants of candidate genes and amplicons were carried out using appropriate restriction enzymes. The copy number of DYZ1 array per haploid genome was calculated using real time PCR and its chromosomal localization was done by fluorescence in-situ hybridization (FISH. Results We studied effects of arsenic exposure on the human Y chromosome in males from different areas of West Bengal focusing on known recombination events (P5-P1 proximal; P5-P1 distal; gr/gr; TSPY-TSPY, b1/b3 and b2/b3, single nucleotide variants (SNVs of a few candidate Y-linked genes (DAZ, TTY4, BPY2, GOLGA2LY and the amplicons of AZFc region. Also, possible chromosomal reorganization of DYZ1 repeat arrays was analyzed. Barring a few microdeletions, no major changes were detected in blood DNA samples. SNV analysis showed a difference in some alleles. Similarly, DYZ1 arrays signals detected by FISH were found to be affected in some males. Conclusions Our Y chromosome analysis suggests that the same is protected from the effects of arsenic by some unknown mechanisms maintaining its structural and functional

  5. Somatosensory deficits in monkeys treated with misonidazole

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  6. The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

    Science.gov (United States)

    Osorio-Yáñez, Citlalli; Chin-Chan, Miguel; Sánchez-Peña, Luz C; Atzatzi-Aguilar, Octavio G; Olivares-Reyes, Jesus A; Segovia, José; Del Razo, Luz M

    2017-08-01

    Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]). Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5μM of arsenite for 24h. We proved that arsenite at 5μM was able to decrease NO levels with an associated increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a decrease in DDAH-1 protein expression with 5μM of arsenite compared to the control group. However, we did not observe significant differences in PRMT-1 protein expression at any of the concentrations of arsenite employed. Finally, arsenite (2.5 and 5μM) increased NADPH oxidase 4 protein levels compared with the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO depletion produced by arsenite, and that the mechanism is related to oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Percutaneous absorption and skin decontamination of PCBs: In vitro studies with human skin and in vivo studies in the rhesus monkey

    International Nuclear Information System (INIS)

    Wester, R.C.; Maibach, H.I.; Bucks, D.A.; McMaster, J.; Mobayen, M.; Sarason, R.; Moore, A.

    1990-01-01

    Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing

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

    Science.gov (United States)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2009-07-01

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

  11. Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

    Science.gov (United States)

    Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

    2012-01-01

    Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

  12. Chromosome aberrations in human lymphocytes exposed to tritiated water in vitro

    International Nuclear Information System (INIS)

    Bocian, E.; Ziemba-zak, B.; Rosiek, O.; Sablinski, J.

    1978-01-01

    The induction of chromosome aberrations in human peripheral blood lymphocytes by tritiated water or 180 kV X-rays in vitro was studied. Lymphocytes were exposed to various concentrations of HTO for 2 h or for 53 h. Chromosome and chromatid type aberrations were scored during the first mitotic division after stimulation with phytohaemagglutinin. For the analysis of the dose-response relationship the data were fitted by the method of least-squares to different models. After acute exposure to tritium β-rays and X-rays, the dicentrics + centric rings and terminal + interstitial deletions gave the best fit to the linear-quadratic function. However, data for these types of aberrations after 53 h exposure to HTO gave equally good fit to the linear and linear-quadratic functions. The best description of the dose-response relationship for chromatid aberrations is given by the linear model. In the system studied the RBE of tritium β-rays as compared to 180 KV X-rays was 1.17+-0.02. (Auth.)

  13. Effects on DNA repair in human lymphocytes exposed to the food dye tartrazine yellow.

    Science.gov (United States)

    Soares, Bruno Moreira; Araújo, Taíssa Maíra Thomaz; Ramos, Jorge Amando Batista; Pinto, Laine Celestino; Khayat, Bruna Meireles; De Oliveira Bahia, Marcelo; Montenegro, Raquel Carvalho; Burbano, Rommel Mario Rodríguez; Khayat, André Salim

    2015-03-01

    Tartrazine is a food additive that belongs to a class of artificial dyes and contains an azo group. Studies about its genotoxic, cytotoxic and mutagenic effects are controversial and, in some cases, unsatisfactory. This work evaluated the potential in vitro cytotoxicity, genotoxicity and effects on DNA repair of human lymphocytes exposed to the dye. We assessed the cytotoxicity of tartrazine by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test and the response of DNA repair through comet assay (alkaline version). We used different concentrations of the dye, ranging from 0.25-64.0 mM. The results demonstrated that tartrazine has no cytotoxic effects. However, this dye had a significant genotoxic effect at all concentrations tested. Although most of the damage was amenable to repair, some damage remained higher than positive control after 24 h of repair. These data demonstrate that tartrazine may be harmful to health and its prolonged use could trigger carcinogenesis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Visual Compensatory Tracking Performance after Exposure to Flashblinding Pulses. I. Comparison of Human and Rhesus Monkey Subjects

    Science.gov (United States)

    1981-04-01

    If different Irom Report) 18. SUPPLEMENTARY NOTES 19. KEY WOROS rContlnuo nrn rever.se ., vde it nee.ssary and rdenrlfy hv brock number) Flashbl...control strategy plays a minor or secondary role in predicting the effects of an insult to the system would be more acceptable. CONCLUSIONS Humans and

  15. Assessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans.

    NARCIS (Netherlands)

    Dubois, V.F.S.; Witte, de W.E.A.; Visser, S.A.; Danhof, M.; Della, Pasqua O.

    2016-01-01

    BACKGROUND AND PURPOSE The selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of the pro-arrhythmic risk of candidate molecules. The objective of this investigation was to assess

  16. A novel exendin-4 human serum albumin fusion protein, E2HSA, with an extended half-life and good glucoregulatory effect in healthy rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ling; Wang, Lin; Meng, Zhiyun; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Gao, Lei; Zhu, Xiaoxia; Sun, Wenzhong; Li, Jian; Zheng, Ying; Dou, Guifang, E-mail: douguifang@vip.163.com

    2014-03-07

    Highlights: • E2HSA has an extended half-life and good plasma stability. • E2HSA could improve glucose-dependent insulin secretion. • E2HSA has excellent glucoregulatory effects in vivo. • E2HSA could potentially be used as a new long-acting GLP-1 receptor agonist for type 2 diabetes management. - Abstract: Glucagon-like peptide-1 (GLP-1) has attracted considerable research interest in terms of the treatment of type 2 diabetes due to their multiple glucoregulatory functions. However, the short half-life, rapid inactivation by dipeptidyl peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the native incretin hormone. Therefore, efforts are being made to develop the long-acting incretin mimetics via modifying its structure. Here we report a novel recombinant exendin-4 human serum albumin fusion protein E2HSA with HSA molecule extends their circulatory half-life in vivo while still retaining exendin-4 biological activity and therapeutic properties. In vitro comparisons of E2HSA and exendin-4 showed similar insulinotropic activity on rat pancreatic islets and GLP-1R-dependent biological activity on RIN-m5F cells, although E2HSA was less potent than exendin-4. E2HSA had a terminal elimation half-life of approximate 54 h in healthy rhesus monkeys. Furthermore, E2HSA could reduce postprandial glucose excursion and control fasting glucose level, dose-dependent suppress food intake. Improvement in glucose-dependent insulin secretion and control serum glucose excursions were observed during hyperglycemic clamp test (18 h) and oral glucose tolerance test (42 h) respectively. Thus the improved physiological characterization of E2HSA make it a new potent anti-diabetic drug for type 2 diabetes therapy.

  17. Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys.

    Science.gov (United States)

    Christ, George J; Andersson, Karl-Erik; Williams, Koudy; Zhao, Weixin; D'Agostino, Ralph; Kaplan, Jay; Aboushwareb, Tamer; Yoo, James; Calenda, Giulia; Davies, Kelvin P; Sellers, Rani S; Melman, Arnold

    2009-12-01

    Despite the advent of effective oral therapies for erectile dysfunction (ED), many patients are not successfully treated, and side effects have been documented. To further evaluate the potential utility of naked DNA-based gene transfer as an attractive treatment option for ED. The effects of gene transfer on erectile function and sexual behavior were evaluated in eight male cynomolgus monkeys with ED secondary to moderately severe, diet-induced atherosclerosis. Following establishment of baseline characteristics, animals were subjected to intracavernous injection of a smooth-muscle-specific gene transfer vector (pSMAA-hSlo) encoding the pore-forming subunit of the human large-conductance, calcium-sensitive potassium channel (Maxi-K). For the sexual behavior studies, 2 wk of baseline data were obtained, and then animals were placed in the presence of estrogen-implanted females (n=2) three times per week for 30 min, and sexual behavior was recorded. The intracavernous pressure response to papaverine injection was also monitored. Dramatic changes in erectile function and sexual behavior were observed after intracorporal gene transfer. The frequency of partial (6±2 to 10±2) and full (2±1.5 to 5±1.4) erections were significantly increased, with a parallel 2-3-fold increase in the duration of the observed erections. The frequency and latency of ejaculation were increased and decreased, respectively. Frequency and duration of grooming by the female were increased, and the latency decreased. Increased latency and decreased frequency of body contact was also observed, and this is characteristic of the typical drop in consort intimacy that occurs after mating in most macaque species. In addition, an increased responsiveness to intracavernous papaverine injection was observed. The data indicate that intracorporal Maxi-K-channel gene transfer enhances erectile capacity and sexual behavior; the data imply that increased erectile function per se may lead to increased sexual

  18. Chromosomal aberrations and DNA damage in human populations exposed to the processing of electronics waste.

    Science.gov (United States)

    Liu, Qiang; Cao, Jia; Li, Ke Qiu; Miao, Xu Hong; Li, Guang; Fan, Fei Yue; Zhao, Yong Cheng

    2009-05-01

    It has been known that the pollutants of electronic wastes (E-wastes) can lead to severe pollution to the environment. It has been reported that about 50% to 80% of E-wastes from developed countries are exported to Asia and Africa. It has become a major global environmental problem to deal with 'E-wastes'. E-waste recycling has remained primitive in Jinghai, China. This not only produces enormous environmental pollution but also can bring about toxic or genotoxic effects on the human body, threatening the health of both current residents and future generations living in the local environment. The concentration of lead in the blood of children in the E-waste polluted area in China is higher than that of the control area. But little is known about the cytogenetic effect to human beings caused by the pollution of E-wastes. In the present study, experiments have been performed to investigate the genetics of permanent residents of three villages with numerous E-waste disposal sites and to analyze the harmful effects of exposure to E-wastes. In total, 171 villagers (exposed group) were randomly selected from permanent residents of three villages located in Jinghai County of Tianjin, China, where there has been massive disposal of E-wastes. Thirty villagers were selected from the neighboring towns without E-waste disposal sites to serve as controls. Chromosomal aberrations and cytokinesis blocking micronucleus were performed to detect the cytogenetic effect, dic + r (dicentric and ring chromosome), monomer, fragments (acentric fragments, minute chromosomes, and acentric rings), translocation, satellite, quadriradial, total aberrations, and micronuclear rate were scored for each subject. DNA damage was detected using comet assay; the DNA percentage in the comet tail (TDNA%), tail moment (TM), and Olive tail moment (OTM) were recorded to describe DNA damage to lymphocytes. The total chromosome aberration rates (5.50%) and micronuclear rates (16.99%) of the exposure group

  19. Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: A modified kinetic approach

    International Nuclear Information System (INIS)

    Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

    2010-01-01

    Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning.

  20. Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.

    Science.gov (United States)

    Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

    2010-12-15

    Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Chromium III histidinate exposure modulates antioxidant gene expression in HaCaT human keratinocytes exposed to oxidative stress

    Science.gov (United States)

    While the toxicity of hexavalent chromium is well established, trivalent Cr (Cr(III)) is an essential nutrient involved in insulin and glucose homeostasis. Recently, antioxidant effects of chromium (III) histidinate (Cr(III)His) were reported in HaCaT human keratinocytes exposed to oxidative stress...

  2. Roles of Human CYP2A6 and Monkey CYP2A24 and 2A26 Cytochrome P450 Enzymes in the Oxidation of 2,5,2',5'-Tetrachlorobiphenyl.

    Science.gov (United States)

    Shimada, Tsutomu; Kakimoto, Kensaku; Takenaka, Shigeo; Koga, Nobuyuki; Uehara, Shotaro; Murayama, Norie; Yamazaki, Hiroshi; Kim, Donghak; Guengerich, F Peter; Komori, Masayuki

    2016-12-01

    2,5,2',5'-Tetrachlorobiphenyl (TCB) induced type I binding spectra with cytochrome P450 (P450) 2A6 and 2A13, with K s values of 9.4 and 0.51 µM, respectively. However, CYP2A6 oxidized 2,5,2',5'-TCB to form 4-hydroxylated products at a much higher rate (∼1.0 minute -1 ) than CYP2A13 (∼0.02 minute -1 ) based on analysis by liquid chromatography-tandem mass spectrometry. Formation of 4-hydroxy-2,5,2',5'-TCB by CYP2A6 was greater than that of 3-hydroxy-2,5,2',5'-TCB and three other hydroxylated products. Several human P450 enzymes, including CYP1A1, 1A2, 1B1, 2B6, 2D6, 2E1, 2C9, and 3A4, did not show any detectable activities in oxidizing 2,5,2',5'-TCB. Cynomolgus monkey CYP2A24, which shows 95% amino acid identity to human CYP2A6, catalyzed 4-hydroxylation of 2,5,2',5'-TCB at a higher rate (∼0.3 minute -1 ) than CYP2A26 (93% identity to CYP2A6, ∼0.13 minute -1 ) and CYP2A23 (94% identity to CYP2A13, ∼0.008 minute -1 ). None of these human and monkey CYP2A enzymes were catalytically active in oxidizing other TCB congeners, such as 2,4,3',4'-, 3,4,3',4'-, and 3,5,3',5'-TCB. Molecular docking analysis suggested that there are different orientations of interaction of 2,5,2',5'-TCB with the active sites (over the heme) of human and monkey CYP2A enzymes, and that ligand interaction energies (U values) of bound protein-ligand complexes show structural relationships of interaction of TCBs and other ligands with active sites of CYP2A enzymes. Catalytic differences in human and monkey CYP2A enzymes in the oxidation of 2,5,2',5'-TCB are suggested to be due to amino acid changes at substrate recognition sites, i.e., V110L, I209S, I300F, V365M, S369G, and R372H, based on the comparison of primary sequences. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Per- and polyfluoroalkyl substances in human serum and urine samples from a residentially exposed community.

    Science.gov (United States)

    Worley, Rachel Rogers; Moore, Susan McAfee; Tierney, Bruce C; Ye, Xiaoyun; Calafat, Antonia M; Campbell, Sean; Woudneh, Million B; Fisher, Jeffrey

    2017-09-01

    Per- and polyfluoroalkyl substances (PFAS) are considered chemicals of emerging concern, in part due to their environmental and biological persistence and the potential for widespread human exposure. In 2007, a PFAS manufacturer near Decatur, Alabama notified the United States Environmental Protection Agency (EPA) it had discharged PFAS into a wastewater treatment plant, resulting in environmental contamination and potential exposures to the local community. To characterize PFAS exposure over time, the Agency for Toxic Substances and Disease Registry (ATSDR) collected blood and urine samples from local residents. Eight PFAS were measured in serum in 2010 (n=153). Eleven PFAS were measured in serum, and five PFAS were measured in urine (n=45) from some of the same residents in 2016. Serum concentrations were compared to nationally representative data and change in serum concentration over time was evaluated. Biological half-lives were estimated for perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) using a one-compartment pharmacokinetic model. In 2010 and 2016, geometric mean PFOA and PFOS serum concentrations were elevated in participants compared to the general U.S. In 2016, the geometric mean PFHxS serum concentration was elevated compared to the general U.S. Geometric mean serum concentrations of PFOA, PFOS, and perfluorononanoic acid (PFNA) were significantly (p≤0.0001) lower (49%, 53%, and 58%, respectively) in 2016 compared to 2010. Half-lives for PFOA, PFOS, and PFHxS were estimated to be 3.9, 3.3, and 15.5years, respectively. Concentrations of PFOA in serum and urine were highly correlated (r=0.75) in males. Serum concentrations of some PFAS are decreasing in this residentially exposed community, but remain elevated compared to the U.S. general population. Published by Elsevier Ltd.

  4. What do monkeys' music choices mean?

    Science.gov (United States)

    Lamont, Alexandra M

    2005-08-01

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

  5. Cellular processes involved in human epidermal cells exposed to extremely low frequency electric fields.

    Science.gov (United States)

    Collard, J-F; Hinsenkamp, M

    2015-05-01

    We observed on different tissues and organisms a biological response after exposure to pulsed low frequency and low amplitude electric or electromagnetic fields but the precise mechanism of cell response remains unknown. The aim of this publication is to understand, using bioinformatics, the biological relevance of processes involved in the modification of gene expression. The list of genes analyzed was obtained after microarray protocol realized on cultures of human epidermal explants growing on deepidermized human skin exposed to a pulsed low frequency electric field. The directed acyclic graph on a WebGestalt Gene Ontology module shows six categories under the biological process root: "biological regulation", "cellular process", "cell proliferation", "death", "metabolic process" and "response to stimulus". Enriched derived categories are coherent with the type of in vitro culture, the stimulation protocol or with the previous results showing a decrease of cell proliferation and an increase of differentiation. The Kegg module on WebGestalt has highlighted "cell cycle" and "p53 signaling pathway" as significantly involved. The Kegg website brings out interactions between FoxO, MAPK, JNK, p53, p38, PI3K/Akt, Wnt, mTor or NF-KappaB. Some genes expressed by the stimulation are known to have an exclusive function on these pathways. Analyses performed with Pathway Studio linked cell proliferation, cell differentiation, apoptosis, cell cycle, mitosis, cell death etc. with our microarrays results. Medline citation generated by the software and the fold change variation confirms a diminution of the proliferation, activation of the differentiation and a less well-defined role of apoptosis or wound healing. Wnt and DKK functional classes, DKK1, MACF1, ATF3, MME, TXNRD1, and BMP-2 genes proposed in previous publications after a manual analysis are also highlighted with other genes after Pathway Studio automatic procedure. Finally, an analysis conducted on a list of genes

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  7. 3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.

    Directory of Open Access Journals (Sweden)

    Manuel A Patarroyo

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

  8. Integrated Analysis of Dysregulated ncRNA and mRNA Expression Profiles in Humans Exposed to Carbon Nanotubes.

    Directory of Open Access Journals (Sweden)

    Anna A Shvedova

    Full Text Available As the application of carbon nanotubes (CNT in consumer products continues to rise, studies have expanded to determine the associated risks of exposure on human and environmental health. In particular, several lines of evidence indicate that exposure to multi-walled carbon nanotubes (MWCNT could pose a carcinogenic risk similar to asbestos fibers. However, to date the potential markers of MWCNT exposure are not yet explored in humans.In the present study, global mRNA and ncRNA expression profiles in the blood of exposed workers, having direct contact with MWCNT aerosol for at least 6 months (n = 8, were compared with expression profiles of non-exposed (n = 7 workers (e.g., professional and/or technical staff from the same manufacturing facility.Significant changes in the ncRNA and mRNA expression profiles were observed between exposed and non-exposed worker groups. An integrative analysis of ncRNA-mRNA correlations was performed to identify target genes, functional relationships, and regulatory networks in MWCNT-exposed workers. The coordinated changes in ncRNA and mRNA expression profiles revealed a set of miRNAs and their target genes with roles in cell cycle regulation/progression/control, apoptosis and proliferation. Further, the identified pathways and signaling networks also revealed MWCNT potential to trigger pulmonary and cardiovascular effects as well as carcinogenic outcomes in humans, similar to those previously described in rodents exposed to MWCNTs.This study is the first to investigate aberrant changes in mRNA and ncRNA expression profiles in the blood of humans exposed to MWCNT. The significant changes in several miRNAs and mRNAs expression as well as their regulatory networks are important for getting molecular insights into the MWCNT-induced toxicity and pathogenesis in humans. Further large-scale prospective studies are necessary to validate the potential applicability of such changes in mRNAs and miRNAs as prognostic markers

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

    National Research Council Canada - National Science Library

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

    2008-01-01

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

  10. Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia

    International Nuclear Information System (INIS)

    Sun, Hong; Shamy, Magdy; Kluz, Thomas; Muñoz, Alexandra B.; Zhong, Mianhua; Laulicht, Freda; Alghamdi, Mansour A.; Khoder, Mamdouh I.; Chen, Lung-Chi; Costa, Max

    2012-01-01

    Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. This study aims to investigate the global gene expression changes in human cells exposed to PM 10 and to identify genes and pathways that may contribute to PM related adverse health effects. Human bronchial epithelial cells were exposed to PM 10 collected from Saudi Arabia for 1 or 4 days, and whole transcript expression was profiled using the GeneChip human gene 1.0 ST array. A total of 140 and 230 genes were identified that significantly changed more than 1.5 fold after PM 10 exposure for 1 or 4 days, respectively. Ingenuity Pathway Analysis revealed that different exposure durations triggered distinct pathways. Genes involved in NRF2-mediated response to oxidative stress were up-regulated after 1 day exposure. In contrast, cells exposed for 4 days exhibited significant changes in genes related to cholesterol and lipid synthesis pathways. These observed changes in cellular oxidative stress and lipid synthesis might contribute to PM related respiratory and cardiovascular disease. -- Highlights: ► PM exposure modulated gene expression and associated pathways in BEAS-2B cells. ► One-day exposure to PM induced genes involved in responding to oxidative stress. ► 4-day exposure to PM changed genes associated to cholesterol and lipid synthesis.

  11. USING PROTEOMICS TO MONITOR PROTEIN EXPRESSION IN HUMAN CELLS EXPOSED TO CARCINOGENS

    Science.gov (United States)

    People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic properties in experimental systems. It has been estimated that exposure to environmental chemical carcinogens in the environment may contribute significantly to t...

  12. Dosimetry of paranasal sinus and mastoid epithelia in radium-exposed humans

    International Nuclear Information System (INIS)

    Schlenker, R.A.

    1981-01-01

    Dose calculations for 228 Ra and 226 Ra are presented for the sinus and mastoid epithelia and lead to the conclusion that the isotopes are of comparable dosimetric significance for the production of carcinomas in patients exposed to comparable levels

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

    Directory of Open Access Journals (Sweden)

    Yasuhiro Uno

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

  14. Cytogenesis in the monkey retina

    International Nuclear Information System (INIS)

    La Vail, M.M.; Rapaport, D.H.; Rakic, P.

    1991-01-01

    Time of cell origin in the retina of the rhesus monkey (Macaca mulatta) was studied by plotting the number of heavily radiolabeled nuclei in autoradiograms prepared from 2- to 6-month-old animals, each of which was exposed to a pulse of 3H-thymidine (3H-TdR) on a single embryonic (E) or postnatal (P) day. Cell birth in the monkey retina begins just after E27, and approximately 96% of cells are generated by E120. The remaining cells are produced during the last (approximately 45) prenatal days and into the first several weeks after birth. Cell genesis begins near the fovea, and proceeds towards the periphery. Cell division largely ceases in the foveal and perifoveal regions by E56. Despite extensive overlap, a class-specific sequence of cell birth was observed. Ganglion and horizontal cells, which are born first, have largely congruent periods of cell genesis with the peak between E38 and E43, and termination around E70. The first labeled cones were apparent by E33, and their highest density was achieved between E43 and E56, tapering to low values at E70, although some cones are generated in the far periphery as late as E110. Amacrine cells are next in the cell birth sequence and begin genesis at E43, reach a peak production between E56 and E85, and cease by E110. Bipolar cell birth begins at the same time as amacrines, but appears to be separate from them temporally since their production reaches a peak between E56 and E102, and persists beyond the day of birth. Mueller cells and rod photoreceptors, which begin to be generated at E45, achieve a peak, and decrease in density at the same time as bipolar cells, but continue genesis at low density on the day of birth. Thus, bipolar, Mueller, and rod cells have a similar time of origin

  15. Behavior of exposed human lymphocytes to a neutron beam of the reactor TRIGA Mark III

    International Nuclear Information System (INIS)

    Carbajal R, M. I.

    2012-01-01

    Excessive exposure to ionizing radiation occurs in people who require radiation treatment, also in those for work can come to receive doses above the permitted levels. A third possibility of exposure is the release of radioactive material in which the general population is affected. Most of the time the exhibition is partial and only rarely occurs throughout the body. For various reasons, situations arise where it is impossible to determine by conventional physical methods, the amount of radiation you were exposed to the affected person and in these cases where the option to follow is the Biological Dosimetry, where the analysis of chromosomes dicentrics is used to estimate the dose of ionizing radiation exposure. A calibration curve is generated from in vitro analysis of dicentric chromosome, which are found in human lymphocytes, treated with different types and doses of radiation. The dicentric is formed from two lesions, one on each chromosome and their union results in a structure having two centromeres, acentric fragment with her for the union of several chromosomes leads to more complex structures as tri-centric s, tetra or penta-centric s, which have the same origin. The dose-response curve is estimated by observing the frequency of dicentrics and extrapolated to a dose-effect curve previously established, for which it is necessary that each lab has its own calibration curves, taking into account that for a Let low radiation, dose-effect curve follows a linear-quadratic model Y=C + αD + βD. The production of dicentric chromosomes with a high Let, was studied using a beam of neutrons generated in the reactor TRIGA Mark III with an average energy of 1 MeV, adjusting the linear model Y=αD. The dose-response relationship is established in blood samples from the same donor, the coefficient α of the dose-response is Y = (0.3692 ± 0.011 * D), also shows that saturation is reached in system 4 Gy. (Author)

  16. Adaptive response in human blood lymphocytes exposed to non-ionizing radiofrequency fields: resistance to ionizing radiation-induced damage.

    Science.gov (United States)

    Sannino, Anna; Zeni, Olga; Romeo, Stefania; Massa, Rita; Gialanella, Giancarlo; Grossi, Gianfranco; Manti, Lorenzo; Vijayalaxmi; Scarfì, Maria Rosaria

    2014-03-01

    The aim of this preliminary investigation was to assess whether human peripheral blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency fields exhibit an adaptive response (AR) by resisting the induction of genetic damage from subsequent exposure to ionizing radiation. Peripheral blood lymphocytes from four healthy donors were stimulated with phytohemagglutinin for 24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR, challenge dose, CD). After a 72 h total culture period, cells were collected to examine the incidence of micronuclei (MN). There was a significant decrease in the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with those subjected to XR alone (CD). These observations thus suggested a RF-induced AR and induction of resistance to subsequent damage from XR. There was variability between the donors in RF-induced AR. The data reported in our earlier investigations also indicated a similar induction of AR in human blood lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different kinds of lesions in cellular DNA, further studies are required to understand the mechanism(s) involved in the RF-induced adaptive response.

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

    Science.gov (United States)

    Basile, Benjamin M; Hampton, Robert R

    2017-09-01

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

  18. Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals

    DEFF Research Database (Denmark)

    Lizeng, Q; Nilsson, C; Sourial, S

    2004-01-01

    Links Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals.Lizeng Q, Nilsson C, Sourial S, Andersson S, Larsen O, Aaby P, Ehnlund M, Bjorling E. Research Center, South Hospital, Stockholm, Sweden. The mechanisms behind...... the resistance to human immunodeficiency virus type 2 (HIV-2) infection are still not fully understood. In the present study, we explored the HIV-2-specific humoral serum immunoglobulin A (IgA) immune response in HIV-2-exposed IgG-seronegative (EGSN) individuals. Serum samples from heterosexual EGSN individuals...... and their known HIV-2-infected partners, as well as controls originating from Guinea-Bissau in Africa, were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated, and the capacity of purified serum IgA to neutralize HIV-2(SBL6669) was tested. Our results showed that 16...

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

    Science.gov (United States)

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

    2009-03-23

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

  20. A Comparison between the Rhesus Monkey and the Human on the Effect of Atropine on the Electroencephalogram. Volume 2. Preliminary Statistical Analysis of Spectral EEG Waveforms in Rhesus Monkeys Exposed to Atropine.

    Science.gov (United States)

    1994-11-01

    000000 000000 000000 000000 000000 C) H rHI HHHH HHHHH - rIr- - rIr H HHHHH 1 1 l H HHHHH- rIr- -I ri - HHHHHH H E-1~~ o~o ~ N H W~r ~ ~ W~MqU) co ýH H aiI...NMlCMMH’DHOO I-NNNMNIr- I- NNNNOnMH U) toH H H z. 000000000 000000000 Cl) H HHHHHH HHHHHHqHHH H- E-4 N MWr-N H Mr- N wMn0~r-oMMN Wl MNHOMM0O’ ro m olq~w H...ý C4k 44 4 ýL 4C 00000 HHH.-4 1- HH H HHHH HHHH U) /u) co* o nvr r-IO NOHM H0(-if0 m i c4 HooD- 00 Z 0000 000000000 00000 VI) H HHHHHH HHHHH HHHH 1

  1. Differential cisplatin responses in human carcinoma cell lines pre-exposed to fractionated X-irradiation

    International Nuclear Information System (INIS)

    Dempke, W.C.M.; Hosking, L.K.; Shellard, S.A.; Hill, B.T.

    1991-01-01

    These results suggest that cells exposed to X-irradiation may respond differently to subsequent cisplatin (CDDP) treatment. Initial studies of possible mechanisms responsible for these differential sensitivities indicate that they may differ according to whether resistance or hypersensitivity is expressed. (author)

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

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

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

  3. Measurement of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins

    International Nuclear Information System (INIS)

    Karlin, J.B.; Juhn, D.J.; Fless, G.; Scanu, A.M.; Rubenstein, A.H.

    1978-01-01

    A sensitive and specific double antibody radioimmunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The antiserum was raised to LDL (d 1.030 to 1.040 g/ml) and the LDL 2 (d 1.020 to 1.050 g/ml) was labeled with 125 I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02 to 0.5 μg of LDL 2 , had an interassay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an average American diet, a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet

  4. Peripheral refraction in normal infant rhesus monkeys

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

    1990-01-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  7. Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

    Directory of Open Access Journals (Sweden)

    Hammond Robert R

    2004-05-01

    Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

  8. Human cytomegalovirus infant infection adversely affects growth and development in maternally HIV-exposed and unexposed infants in Zambia.

    Science.gov (United States)

    Gompels, U A; Larke, N; Sanz-Ramos, M; Bates, M; Musonda, K; Manno, D; Siame, J; Monze, M; Filteau, S

    2012-02-01

    Human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) coinfections have been shown to increase infant morbidity, mortality, and AIDS progression. In HIV-endemic regions, maternal HIV-exposed but HIV-uninfected infants, which is the majority of children affected by HIV, also show poor growth and increased morbidity. Although nutrition has been examined, the effects of HCMV infection have not been evaluated. We studied the effects of HCMV infection on the growth, development, and health of maternally HIV-exposed and unexposed infants in Zambia. Infants were examined in a cohort recruited to a trial of micronutrient-fortified complementary foods. HIV-infected mothers and infants had received perinatal antiretroviral therapy to prevent mother-to-child HIV transmission. Growth, development, and morbidity were analyzed by linear regression analyses in relation to maternal HIV exposure and HCMV infection, as screened by sera DNA for viremia at 6 months of age and by antibody for infection at 18 months. All HCMV-seropositive infants had decreased length-for-age by 18 months compared with seronegative infants (standard deviation [z]-score difference: -0.44 [95% confidence interval {CI}, -.72 to -.17]; P = .002). In HIV-exposed infants, those who were HCMV positive compared with those who were negative, also had reduced head size (mean z-score difference: -0.72 [95% CI, -1.23 to -.22]; P = .01) and lower psychomotor development (Bayley test score difference: -4.1 [95% CI, -7.8 to -.5]; P = .03). HIV-exposed, HCMV-viremic infants were more commonly referred for hospital treatment than HCMV-negative infants. The effects of HCMV were unaffected by micronutrient fortification. HCMV affects child growth, development, and morbidity of African infants, particularly in those maternally exposed to HIV. HCMV is therefore a risk factor for child health in this region.

  9. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Wong Brian A

    2005-10-01

    Full Text Available Abstract Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is

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

    Directory of Open Access Journals (Sweden)

    Elsa Addessi

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

  11. Increased frequency of micronucleated exfoliated cells among humans exposed in vivo to mobile telephone radiations

    International Nuclear Information System (INIS)

    Manoj Kumar Sharma; Abhay Singh Yadav

    2007-01-01

    Complete text of publication follows. The health concerns have been raised following the enormous increase in the use of wireless mobile telephones through out the world. This investigation had been taken, with the motive to find out whether mobile phone radiations cause any in vivo effects on the frequency of micronucleated exfoliated cells in the exposed subjects. A total of 109 subjects including 85 regular mobile phone users (exposed) and 24 non-users (controls) had participated in this study. Exfoliated cells were obtained by swabbing the buccal-mucosa from exposed as well as sex-age-matched controls. One thousand exfoliated cells were screened from each individual for nuclear anomalies including micronuclei (MN), karyolysis (KL), karyorrhexis (KH), broken egg (BE) and bi-nucleated (BN) cells. The average daily duration of exposure to mobile phone radiations is 61.26 minutes with an overall average duration of exposure in term of years is 2.35 years in exposed subjects along with the 9.84±0.745 MNC (micronucleated cells) and 10.72±0.889 TMN (total micronuclei) as compared to zero duration of exposure along with average 3.75±0.774 MNC and 4.00±0.808 TMN in controls. The means are significantly different in case MNC and TMN at 0.01% level of significance. For all other nuclear anomalies (KL, KH, BE and BN cells) the means are found statistically nonsignificant. A positive correlation was found in the frequency of MNC and TMN with respect to duration of exposure time.

  12. Reduction in life span on normal human fibroblasts exposed to low-dose radiation in heavy-ion radiation field

    International Nuclear Information System (INIS)

    Suzuki, Masao; Yamaguchi, Chizuru; Yasuda, Hiroshi; Uchihori, Yukio; Fujitaka, Kazunobu

    2003-01-01

    We studied the effect of in vitro life span in normal human fibroblasts exposed to chronically low-dose radiation in heavy-ion radiation field. Cells were cultured in a CO 2 incubator, which was set in the irradiation room for biological study of heavy ions in the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS), and exposed to scattered radiations produced with heavy-ion beams throughout the life span of the cell population. Absorbed dose, which was measured using a thermoluminescence dosimeter(TLD) and a Si-semiconductor detector, was to be 1.4 mGy per day when operating the HIMAC machine for biological experiments. The total population doubling number of the exposed cells reduced to 79-93% of non-exposed control cells in the three independent experiments. There is evidence that the exposure of chronically low-dose radiation in heavy-ion radiation field promotes the life-span reduction in cellular level. (author)

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

    Directory of Open Access Journals (Sweden)

    Adachi Akio

    2009-08-01

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

  14. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

    Science.gov (United States)

    Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

    1996-01-01

    Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

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

    OpenAIRE

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

    2014-01-01

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

  16. Electric fields and currents induced in organs of the human body when exposed to ELF and VLF electromagnetic fields

    Science.gov (United States)

    King, Ronold W. P.; Sandler, Sheldon S.

    1996-09-01

    Formulas for the transverse components of the electric and magnetic fields of the traveling-wave currents of three different types of three-wire, three-phase high-voltage power lines and of a typical VLF transmitter are given. From them, exposure situations for the human body are chosen which permit the analytical determination of the total current induced in that body. With this, the fraction of the total axial current, the axial current density, and the axial electric field in each organ of the body are obtained at any desired cross section. The dimensions and conductivity of these organs must be known. The electric field so obtained is the average macroscopic field in which the cells in each organ are immersed when the whole body is exposed to a known incident field. It corresponds in vivo to the electric field used in vitro to expose cells in tissues.

  17. COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

    Science.gov (United States)

    The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

  18. Hemorrhoids: an experimental model in monkeys

    Directory of Open Access Journals (Sweden)

    Plapler Hélio

    2006-01-01

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

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

    Science.gov (United States)

    Tu, Hsiao-Wei; Hampton, Robert R.

    2014-01-01

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

  20. Prenatal methylmercury exposure affects spatial vision in adult monkeys

    International Nuclear Information System (INIS)

    Burbacher, Thomas M.; Grant, Kimberly S.; Mayfield, David B.; Gilbert, Steven G.; Rice, Deborah C.

    2005-01-01

    Decades of research have demonstrated that exposure to methylmercury (MeHg), a ubiquitous environmental pollutant, can have both early and long-term neurobehavioral consequences in exposed offspring. The present study assessed visual functioning in adult macaque monkeys (Macaca fascicularis) exposed in utero to 0, 50, 70, or 90 μg/kg/day of MeHg hydroxide. Twenty-one full-term, normal birth weight offspring (9 controls, 12 exposed) were tested at approximately 11-14.5 years of age on a visual contrast sensitivity task. A forced-choice tracking procedure was utilized with spatial frequencies of 1, 4, 10, and 20 cycles per degree of visual angle. On each test session, a single spatial frequency was presented across five levels of contrast, each differing by 3 dB. Methylmercury-exposed monkeys exhibited reduced contrast sensitivity thresholds, particularly at the higher spatial frequencies. The degree of visual impairment was not related to MeHg body burden or clearance and almost half of the exposed animals were unimpaired. The results from this study demonstrate that chronic in utero MeHg exposure, at subclinical levels, is associated with permanent adverse effects on spatial vision in adult monkeys

  1. Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

    DEFF Research Database (Denmark)

    Kessel, Line; Eskildsen, Lars; Lundeman, Jesper Holm

    2011-01-01

    region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation. METHODS: Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm) lasers......: Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after irradiation...

  2. Optical effects of exposing intact human lenses to ultraviolet radiation and visible light

    DEFF Research Database (Denmark)

    Kessel, Line; Eskildsen, Lars Baunsgaard; Lundeman, Jesper Holm

    2011-01-01

    wavelength region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation. METHODS: Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm....... RESULTS: Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after...

  3. Face Pareidolia in the Rhesus Monkey.

    Science.gov (United States)

    Taubert, Jessica; Wardle, Susan G; Flessert, Molly; Leopold, David A; Ungerleider, Leslie G

    2017-08-21

    Face perception in humans and nonhuman primates is rapid and accurate [1-4]. In the human brain, a network of visual-processing regions is specialized for faces [5-7]. Although face processing is a priority of the primate visual system, face detection is not infallible. Face pareidolia is the compelling illusion of perceiving facial features on inanimate objects, such as the illusory face on the surface of the moon. Although face pareidolia is commonly experienced by humans, its presence in other species is unknown. Here we provide evidence for face pareidolia in a species known to possess a complex face-processing system [8-10]: the rhesus monkey (Macaca mulatta). In a visual preference task [11, 12], monkeys looked longer at photographs of objects that elicited face pareidolia in human observers than at photographs of similar objects that did not elicit illusory faces. Examination of eye movements revealed that monkeys fixated the illusory internal facial features in a pattern consistent with how they view photographs of faces [13]. Although the specialized response to faces observed in humans [1, 3, 5-7, 14] is often argued to be continuous across primates [4, 15], it was previously unclear whether face pareidolia arose from a uniquely human capacity. For example, pareidolia could be a product of the human aptitude for perceptual abstraction or result from frequent exposure to cartoons and illustrations that anthropomorphize inanimate objects. Instead, our results indicate that the perception of illusory facial features on inanimate objects is driven by a broadly tuned face-detection mechanism that we share with other species. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Phenotypic and genotypic characterization of antioxidant enzyme system in human population exposed to radiation from mobile towers.

    Science.gov (United States)

    Gulati, Sachin; Yadav, Anita; Kumar, Neeraj; Priya, Kanu; Aggarwal, Neeraj K; Gupta, Ranjan

    2018-03-01

    In the present era, cellular phones have changed the life style of human beings completely and have become an essential part of their lives. The number of cell phones and cell towers are increasing in spite of their disadvantages. These cell towers transmit radiation continuously without any interruption, so people living within 100s of meters from the tower receive 10,000 to 10,000,000 times stronger signal than required for mobile communication. In the present study, we have examined superoxide dismutase (SOD) enzyme activity, catalase (CAT) enzyme activity, lipid peroxidation assay, and effect of functional polymorphism of SOD and CAT antioxidant genes against mobile tower-induced oxidative stress in human population. From our results, we have found a significantly lower mean value of manganese superoxide dismutase (MnSOD) enzyme activity, catalase (CAT) enzyme activity, and a high value of lipid peroxidation assay in exposed as compared to control subjects. Polymorphisms in antioxidant MnSOD and CAT genes significantly contributed to its phenotype. In the current study, a significant association of genetic polymorphism of antioxidant genes with genetic damage has been observed in human population exposed to radiations emitted from mobile towers.

  6. Cytotoxic and inflammatory responses of human lung cells exposed to multi-walled carbon nanotubes

    OpenAIRE

    Nilsen, Lone

    2011-01-01

    AbstractWith the emergence of the nanotechnology industry, there has been a rapid expansion of different types and numbers of nanomaterials to be used in various applications. However, little is known of their potential to cause harmful effects on human health. Among other nanomaterials, carbon nanotubes, are found to harbor attractive characteristics that can be used in many applications. However, the same properties may cause harmful effects on human health that has raised serious concerns....

  7. The Thermal Plume above a Standing Human Body Exposed to Different Air Distribution Strategies

    DEFF Research Database (Denmark)

    Liu, Li; Nielsen, Peter V.; Li, Yuguo

    2009-01-01

    This study compares the impact of air distribution on the thermal plume above a human body in indoor environment. Three sets of measurements are conducted in a full-scale test room with different ventilation conditions. One breathing thermal manikin standing in the room is used to simulate...... the human body. Long-time average air velocity profiles at locations closely above the manikin are taken to identify the wandering thermal plume....

  8. Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol.

    Science.gov (United States)

    Donejko, Magdalena; Rysiak, Edyta; Galicka, Elżbieta; Terlikowski, Robert; Głażewska, Edyta Katarzyna; Przylipiak, Andrzej

    2017-01-01

    The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol.

  9. Head Rotation Detection in Marmoset Monkeys

    Science.gov (United States)

    Simhadri, Sravanthi

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

  10. PCC-ring induction in human lymphocytes exposed to gamma and neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lamadrid Boada, Ana I; Garcia Lima, Omar [Centro de Proteccion e Higiene de las Radiaciones (CPHR), La Habana (Cuba); Delbos, Martine; Voisin, Philipe; Roy, Laurence [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France)

    2008-07-01

    Dose-effect curves for dose assessment in Gamma and neutron overexposures to high doses are presented in this paper for the first time in literature. The relationships were obtained by plotting the Premature Chromosome Condensation -rings (PCC-R) frequencies in PCC lymphocytes obtained by chemical induction with Calyculin A in vitro, with radiation doses between 5 to 25 Gy. For the elaboration of these curves 9 676 PCC cells in G1 G2 and M stages were analyzed. The results were fitted to a lineal quadratic model in Gamma irradiation and showed saturation starting from 20 Gy. For neutron irradiation the data was fitted to a lineal quadratic model up to 10 Gy, and then a markedly cell cycle arrest and saturation was observed. These curves are of particular interest for victims exposed to doses exceeding 5 Gy where it is always very difficult to estimate a dose using the conventional technique. (author)

  11. PCC-ring induction in human lymphocytes exposed to gamma and neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lamadrid B, A I; Garcia L, O [CPHR, Calle 20 No. 4113 e/41 y 47, Playa, La Habana 11300 (Cuba); Delbos, M; Voisin, P; Roy, L [Institut de Radioprotection et de Surete Nucleaire, BP 17, 92262 Fontenay-aux-Roses (France)

    2006-07-01

    Dose-effect curves for dose assessment in Gamma and neutron overexposures to high doses are presented in this paper for the first time in literature. The relationships were obtained by plotting the Premature Chromosome Condensation -rings (PCC-R) frequencies in PCC Iymphocytes obtained by chemical induction with Calyculin A in vitro, with radiation doses between 5 to 25 Gy. For the elaboration of these curves 9 676 PCC cells in Gl G2 and M stages were analyzed. The results were fitted to a lineal quadratic model in Gamma irradiation. For neutron irradiation the data was fitted to a lineal quadratic model up to 10 Gy and then a markedly cell cycle arrest and saturation was observed. These curves are of particular interest for victims exposed to doses exceeding 5 Gy where it is always very difficult to estimate a dose using the conventional technique. (Author)

  12. PCC-ring induction in human lymphocytes exposed to gamma and neutron irradiation

    International Nuclear Information System (INIS)

    Lamadrid B, A.I.; Garcia L, O.; Delbos, M.; Voisin, P.; Roy, L.

    2006-01-01

    Dose-effect curves for dose assessment in Gamma and neutron overexposures to high doses are presented in this paper for the first time in literature. The relationships were obtained by plotting the Premature Chromosome Condensation -rings (PCC-R) frequencies in PCC Iymphocytes obtained by chemical induction with Calyculin A in vitro, with radiation doses between 5 to 25 Gy. For the elaboration of these curves 9 676 PCC cells in Gl G2 and M stages were analyzed. The results were fitted to a lineal quadratic model in Gamma irradiation. For neutron irradiation the data was fitted to a lineal quadratic model up to 10 Gy and then a markedly cell cycle arrest and saturation was observed. These curves are of particular interest for victims exposed to doses exceeding 5 Gy where it is always very difficult to estimate a dose using the conventional technique. (Author)

  13. PCC-ring induction in human lymphocytes exposed to gamma and neutron irradiation

    International Nuclear Information System (INIS)

    Lamadrid Boada, Ana I.; Garcia Lima, Omar; Delbos, Martine; Voisin, Philipe; Roy, Laurence

    2008-01-01

    Dose-effect curves for dose assessment in Gamma and neutron overexposures to high doses are presented in this paper for the first time in literature. The relationships were obtained by plotting the Premature Chromosome Condensation -rings (PCC-R) frequencies in PCC lymphocytes obtained by chemical induction with Calyculin A in vitro, with radiation doses between 5 to 25 Gy. For the elaboration of these curves 9 676 PCC cells in G1 G2 and M stages were analyzed. The results were fitted to a lineal quadratic model in Gamma irradiation and showed saturation starting from 20 Gy. For neutron irradiation the data was fitted to a lineal quadratic model up to 10 Gy, and then a markedly cell cycle arrest and saturation was observed. These curves are of particular interest for victims exposed to doses exceeding 5 Gy where it is always very difficult to estimate a dose using the conventional technique. (author)

  14. Evaluation of T-lymphocyte populations in humans exposed to action of beryllium compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ermakova, N G

    1977-10-01

    Earlier studies in vitro on beryllosis and cellular immunity, and knowledge of the role of T-cells in development of cellular immunity suggested usefulness of a quantitative determination of T-cell populations in beryllosis. Assay was based on the test for spontaneous rosette formation in beryllosis patients and in healthy workers who come in contact with Be compounds (Jondal, modified by M. A. Stenina) and on the leucocyte migration inhibition reaction (Soborg and Bendixen). A large range of changes were revealed in population size and in adhesion qualities of T-lymphocytes in the patients and in those exposed to Be. The test for spontaneous rosette formation was found to be sufficiently indicative for use in study of beryllosis pathogenesis and to correlate with the state of activity of the disease.

  15. Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver

    Directory of Open Access Journals (Sweden)

    Saura C. Sahu

    Full Text Available Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in vitro models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable in vitro tool for assessing toxicity of nanomaterials such as nanosilver. Keywords: Nanosilver, Silver nanoparticles, Nanoparticles, Toxicogenomics, DNA microarray, Global gene expression profiles, Caco2 cells

  16. Hepatic Proteome Sensitivity in Rainbow Trout after Chronically Exposed to a Human Pharmaceutical Verapamil*

    Science.gov (United States)

    Li, Zhi-Hua; Li, Ping; Sulc, Miroslav; Hulak, Martin; Randak, Tomas

    2012-01-01

    Verapamil (VRP), a cardiovascular pharmaceutical widely distributed and persistent in the aquatic environment, has potential toxicity to fish and other aquatic organisms. However, the molecular mechanisms that lead to these toxic effects are not well known. In the present study, proteomic analysis has been performed to investigate the protein patterns that are differentially expressed in liver of rainbow trout exposed to sublethal concentrations of VRP (0.5, 27.0, and 270 μg/liter) for 42 days. Two-dimensional electrophoresis coupled with MALDI-TOF/TOF mass spectrometry was employed to detect and identify the protein profiles. The analysis revealed that the expression of six hepatic acidic proteins were markedly altered in the treatment groups compared with the control group; three proteins especially were significantly down-regulated in fish exposed to VRP at environmental related concentration (0.5 μg/liter). These results suggested that the VRP induce mechanisms against oxidative stress (glucose-regulated protein 78 and 94 and protein disulfide-isomerase A3) and adaptive changes in ion transference regulation (calreticulin, hyperosmotic glycine-rich protein). Furthermore, for the first time, protein Canopy-1 was found to be significantly down-regulated in fish by chronic exposure to VRP at environmental related levels. Overall, our work supports that fish hepatic proteomics analysis serves as an in vivo model for monitoring the residual pharmaceuticals in aquatic environment and can provide valuable insight into the molecular events in VRP-induced toxicity in fish and other organisms. PMID:21997734

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

    Directory of Open Access Journals (Sweden)

    Watson Karli K

    2012-07-01

    Full Text Available Abstract The autism spectrum disorders (ASDs arise from a diverse array of genetic and environmental origins that disrupt the typical developmental trajectory of neural connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior and cognition, among other deficits. Greater understanding of the biological substrates of typical social behavior in animal models will further our understanding of the etiology of ASDs. Despite the precision and tractability of molecular genetics models of ASDs in rodents, these organisms lack the complexity of human social behavior, thus limiting their impact on understanding ASDs to basic mechanisms. Non-human primates (NHPs provide an attractive, complementary model for ASDs, due in part to the complexity and dynamics of social structures, reliance on vision for social signaling, and deep homology in brain circuitry mediating social behavior and reward. This knowledge is based on a rich literature, compiled over 50 years of observing primate behavior in the wild, which, in the case of rhesus macaques, is complemented by a large body of research characterizing neuronal activity during cognitive behavior. Several recent developments in this field are directly relevant to ASDs, including how the brain represents the perceptual features of social stimuli, how social information influences attention processes in the brain, and how the value of social interaction is computed. Because the symptoms of ASDs may represent extreme manifestations of traits that vary in intensity within the general population, we will additionally discuss ways in which nonhuman primates also show variation in social behavior and reward sensitivity. In cases where variation in species-typical behavior is analogous to similar variations in human behavior, we believe that study of the neural circuitry underlying this variation will provide important insights into the systems-level mechanisms contributing to ASD pathology.

  18. Relationship between human respiratory reactivity and neutrophil metabolism under intermittent hypoxic influences in humans exposed to low-level radiation

    International Nuclear Information System (INIS)

    Serebrovskaya, T.V.; Oberenko, O.A.; Guseva, S.A.

    1996-01-01

    The group of 18 men exposed to radiation during amelioration work in the Chernobyl NPP was examined in the course of adaptation to intermittent hypoxia (rebreathing technique during 10 days of three dayly 5-7 min sessions with 15 min break). The starting level of ventilatory response to hypoxic stimulus (HVR) did not differ from the one in persons living in non-contaminated areas. This hypoxic training (HT) caused the increase of HVR, activity of NADPH-oxidase and cationic protein content in neutrophyls as well as various changes in mieloperoxidase activity. The correlation between respiration reactivity and deviations in neutrophil metabolism under HT was found. 14 refs., 2 figs

  19. Study on differential transcriptional profile in human hepatocyte exposed to different doses γ ray

    International Nuclear Information System (INIS)

    Li Jianguo; Wen Jianhua; Duan Zhikai; Tian Yu; Wang Fang; Zuo Yahui

    2009-01-01

    The study analyzed the differential transcriptional profile of normal human hepatic cell and human hepatic cell radiated with three different doses (0.5 Gy, 2 Gy, 4 Gy γ ray) by gene chip technique. The results showed that the whole differentially expressed genes of three different doses have 284 in 14112 human genes analyzed, in which 261 genes were up-regulated and 23 genes were down-regulated. These genes are mainly associated with interferon receptor, mitochondrial regulation, homo sapiens hepatitis A virus cellular receptor, cell cycle regulation, kinase and zinc finger protein etc. RT-PCR results indicated that up-regulated expression of gene HAVcr-1, HAVcr-2, MFTC, MOAP1 and down-regulated expression of gene TRIP12, DCN are consistent with gene chip data. (authors)

  20. Study of differential gene expression in human hepatocyte exposed to 50 cGy γ ray

    International Nuclear Information System (INIS)

    Wen Jianhua; Li Jianguo; Tian Huancheng; Li Yanling; Wang Xiaoli; Zuo Yanhui

    2008-01-01

    The study analyzed the differential transcriptional profile of the normal human hepatic cell and the human hepatic cell radiated with 50 cGy γ ray by gene chip technique. The results showed that there were 614 differentially expressed genes among 14 112 human genes analyzed, in which 521 genes were up-regulated and 93 genes down-regulated. These genes are associated with mitochondrial regulation, homo sapiens hepatitis A virus cellular receptor, tumor necrosis factor, cell cycle regulation, kinase and zinc finger protein etc. RT-PCR results indicated that up-regulated expression of gene HAVcr-1, HAVcr-2, MFTC, MOAP1 and down-regulated expression of gene TRIP12, DCN were consistent with gene chip data. (authors)

  1. Changes in silver nanoparticles exposed to human synthetic stomach fluid: Effectsof particle size and surface chemistry

    Science.gov (United States)

    The significant rise in consumer products and applications utilizing the antibacterial properties of silver nanoparticles (AgNPs) has increased the possibility of human exposure. The mobility and bioavailability of AgNPs through the ingestion pathway will depend, in part, on prop...

  2. Dose-dependent micronuclei formation in normal human fibroblasts exposed to proton radiation

    Czech Academy of Sciences Publication Activity Database

    Litvinchuk, Alexandra; Vachelová, Jana; Michaelidesová, Anna; Wagner, Richard; Davídková, Marie

    2015-01-01

    Roč. 54, č. 3 (2015), s. 327-334 ISSN 0301-634X R&D Projects: GA ČR(CZ) GBP108/12/G108; GA MŠk LM2011019 Institutional support: RVO:61389005 Keywords : human fibroblasts * proton radiation * micronuclei assay * biodosimetry Subject RIV: BO - Biophysics Impact factor: 1.923, year: 2015

  3. Global gene expression changes in human urothelial cells exposed to low-level monomethylarsonous acid

    Czech Academy of Sciences Publication Activity Database

    Medeiros, M.; Zheng, X.; Novák, Petr; Wnek, S.M.; Chyan, V.; Escudero-Lourdes, C.; Gandolfi, A.J.

    2012-01-01

    Roč. 291, 1-3 (2012), s. 102-112 ISSN 0300-483X Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : HUMAN BLADDER CELLS * METHYLATED TRIVALENT ARSENICALS * MALIGNANT-TRANSFORMATION0300 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.017, year: 2012

  4. Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

    DEFF Research Database (Denmark)

    Lundby, Carsten; Pilegaard, Henriette; van Hall, Gerrit

    2003-01-01

    Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming...

  5. Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene.

    Science.gov (United States)

    Jiang, Yan; Wang, Dan; Zhang, Guoxing; Wang, Guoqing; Tong, Jian; Chen, Tao

    2016-11-01

    Trichloroethylene (TCE) is ubiquitous in our living environment, and prenatal exposure to TCE is reported to cause congenital heart disease in humans. Although multiple studies have been performed using animal models, they have limited value in predicting effects on humans due to the unknown species-specific toxicological effects. To test whether exposure to low doses of TCE induces developmental toxicity in humans, we investigated the effect of TCE on human embryonic stem cells (hESCs) and cardiomyocytes (derived from the hESCs). In the current study, hESCs cardiac differentiation was achieved by using differentiation medium consisting of StemPro-34. We examined the effects of TCE on cell viability by cell growth assay and cardiac inhibition by analysis of spontaneously beating cluster. The expression levels of genes associated with cardiac differentiation and Ca 2+ channel pathways were measured by immunofluorescence and qPCR. The overall data indicated the following: (1) significant cardiac inhibition, which was characterized by decreased beating clusters and beating rates, following treatment with low doses of TCE; (2) significant up-regulation of the Nkx2.5/Hand1 gene in cardiac progenitors and down regulation of the Mhc-7/cTnT gene in cardiac cells; and (3) significant interference with Ca 2+ channel pathways in cardiomyocytes, which contributes to the adverse effect of TCE on cardiac differentiation during early embryo development. Our results confirmed the involvement of Ca 2+ turnover network in TCE cardiotoxicity as reported in animal models, while the inhibition effect of TCE on the transition of cardiac progenitors to cardiomyocytes is unique to hESCs, indicating a species-specific effect of TCE on heart development. This study provides new insight into TCE biology in humans, which may help explain the development of congenital heart defects after TCE exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1372-1380, 2016. © 2015 Wiley

  6. Changes in silver nanoparticles exposed to human synthetic stomach fluid: Effects of particle size and surface chemistry

    International Nuclear Information System (INIS)

    Mwilu, Samuel K.; El Badawy, Amro M.; Bradham, Karen; Nelson, Clay; Thomas, David; Scheckel, Kirk G.; Tolaymat, Thabet; Ma, Longzhou; Rogers, Kim R.

    2013-01-01

    The significant rise in consumer products and applications utilizing the antibacterial properties of silver nanoparticles (AgNPs) has increased the possibility of human exposure. The mobility and bioavailability of AgNPs through the ingestion pathway will depend, in part, on properties such as particle size and the surface chemistries that will influence their physical and chemical reactivities during transit through the gastrointestinal tract. This study investigates the interactions between synthetic stomach fluid and AgNPs of different sizes and with different capping agents. Changes in morphology, size and chemical composition were determined during a 30 min exposure to synthetic human stomach fluid (SSF) using Absorbance Spectroscopy, High Resolution Transmission Electron and Scanning Electron Microscopy (TEM/SEM), Dynamic Light Scattering (DLS), and Nanoparticle Tracking Analysis (NTA). AgNPs exposed to SSF were found to aggregate significantly and also released ionic silver which physically associated with the particle aggregates as silver chloride. Generally, the smaller sized AgNPs (< 10 nm) showed higher rates of aggregation and physical transformation than larger particles (75 nm). Polyvinylpyrrolidone (pvp)-stabilized AgNPs prepared in house behaved differently in SSF than particles obtained from a commercial source despite having similar surface coating and size distribution characteristics. - Highlights: ► Interactions between synthetic stomach fluid (SSF) and silver nanoparticles (AgNPs) are described. ► AgNPs exposed to SSF aggregate and silver chloride are associated with the particle aggregates. ► Smaller AgNPs (< 10 nm) showed higher rates of aggregation and transformation than larger particles (75 nm). ► Polyvinylpyrrolidone-stabilized AgNPs obtained from different sources aggregated at different rates when exposed to SSF

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

    Science.gov (United States)

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

    2001-01-01

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

  8. Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

    Directory of Open Access Journals (Sweden)

    Victor Paromov

    2011-01-01

    Full Text Available Sulfur mustard or mustard gas (HD and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES, or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes increased cell viability and attenuated production of reactive oxygen species (ROS in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

  9. Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

    International Nuclear Information System (INIS)

    Seyyedi, S. S.; Mozdarani, H.; Rezaei Tavirani, M.; Heydari, S.

    2010-01-01

    Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to extremely low-frequency electromagnetic fields may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk estimation. Materials and Methods: Primary cultures of fibroblasts from human skin biopsy were exposed to continuous extremely low-frequency electromagnetic fields (3, 50 and 60 Hz, sinusoidal, 3h, and 4 m T). Also immortalized cell lines, SW480, MCF-7 and 1321N1 were exposed to continuous extremely low-frequency electromagnetic fields (50 Hz, sinusoidal, 3 h, 4 m T). Metaphase plates Were prepared according to standard methods and stained in 5% Giemsa solution. Chromosomal aberrations of both chromosome and chromatid types were scored to evaluate the effects of extremely low-frequency electromagnetic fields on primary or established cell lines. Results: Results indicate that by increasing the frequency of extremely low-frequency electromagnetic fields, chromosomal aberrations were increased up to 7-fold above background levels in primary human fibroblast cells. In addition, continuous exposure to a 50 Hz electromagnetic field led to a significant increase in chromosomal aberrations in SW480, MCF-7 and 1321N1 cell lines compared to sham control. Conclusion: Results obtained indicate that extremely low-frequency electromagnetic fields has the potential for induction of chromosomal aberrations in all cell types.

  10. Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

    National Research Council Canada - National Science Library

    Gao1, Radharaman Ray2, Yan Xiao3, Peter E. Barker3 and Prab, Xiugong

    2006-01-01

    .... In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE...

  11. Spermatogenesis in adult rhesus monkeys following irradiation with X-rays or fission neutrons

    International Nuclear Information System (INIS)

    Rooij, D.G. de; Sonneveld, P.; Bekkum, D.W. van

    A group of male rhesus monkeys was exposed to total body irradiation followed by autologous bone marrow transplantation. The animals were irradiated in the period between 1965 and 1976 and received a dose of 8.5 Gy of X-rays (300 KVP) or 3.6 Gy of 1 MeV fission neutrons. Of this group, a total of 11 male monkeys proved to be evaluable for studying the effects of irradiation on spermatogenesis. (Auth.)

  12. What Do Monkey Calls Mean?

    Science.gov (United States)

    Schlenker, Philippe; Chemla, Emmanuel; Zuberbühler, Klaus

    2016-12-01

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

  13. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

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

    2015-02-18

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

  14. S6-5: Visual Consciousness Tracked with Direct Intracranial Recording from Early and High-Level Visual Cortices in Humans and Monkeys

    Directory of Open Access Journals (Sweden)

    Naotsugu Tsuchiya

    2012-10-01

    Full Text Available Key insights about the neuronal correlates of consciousness have been gained by electrophysiological recording of single neurons from a particular area or by recording of indirect fMRI signals from the whole brain. However, if rapid interaction among neuronal populations in distant cortical areas is essential for consciousness, other methods such as intracranial electrocorticogram (ECoG that can attain both requirements are necessary. Here we report the results of ECoG experiments in three epilepsy patients and one monkey. We used Continuous Flash Suppression to investigate the neuronal activity when ‘invisible’ stimuli broke interocular suppression. We found that widespread activity in the visual cortex preceded up to 1–2 s before subjective reports of detection and that alpha-band activity in the visual cortex induced by the initial flashes predicted how long the suppression was going to last. We will discuss implication of these findings for the neuronal dynamics associated with consciousness.

  15. Structural and molecular insights into novel surface-exposed mucus adhesins from Lactobacillus reuteri human strains.

    Science.gov (United States)

    Etzold, Sabrina; MacKenzie, Donald A; Jeffers, Faye; Walshaw, John; Roos, Stefan; Hemmings, Andrew M; Juge, Nathalie

    2014-05-01

    The mucus layer covering the gastrointestinal tract is the first point of contact of the intestinal microbiota with the host. Cell surface macromolecules are critical for adherence of commensal bacteria to mucus but structural information is scarce. Here we report the first molecular and structural characterization of a novel cell-surface protein, Lar_0958 from Lactobacillus reuteri JCM 1112(T) , mediating adhesion of L. reuteri human strains to mucus. Lar_0958 is a modular protein of 133 kDa containing six repeat domains, an N-terminal signal sequence and a C-terminal anchoring motif (LPXTG). Lar_0958 homologues are expressed on the cell-surface of L. reuteri human strains, as shown by flow-cytometry and immunogold microscopy. Adhesion of human L. reuteri strains to mucus in vitro was significantly reduced in the presence of an anti-Lar_0958 antibody and Lar_0958 contribution to adhesion was further confirmed using a L. reuteri ATCC PTA 6475 lar_0958 KO mutant (6475-KO). The X-ray crystal structure of a single Lar_0958 repeat, determined at 1.5 Å resolution, revealed a divergent immunoglobulin (Ig)-like β-sandwich fold, sharing structural homology with the Ig-like inter-repeat domain of internalins of the food borne pathogen Listeria monocytogenes. These findings provide unique structural insights into cell-surface protein repeats involved in adhesion of Gram-positive bacteria to the intestine. © 2014 John Wiley & Sons Ltd.

  16. DNA damage in human germ cell exposed to the some food additives in vitro.

    Science.gov (United States)

    Pandir, Dilek

    2016-08-01

    The use of food additives has increased enormously in modern food technology but they have adverse effects in human healthy. The aim of this study was to investigate the DNA damage of some food additives such as citric acid (CA), benzoic acid (BA), brilliant blue (BB) and sunset yellow (SY) which were investigated in human male germ cells using comet assay. The sperm cells were incubated with different concentrations of these food additives (50, 100, 200 and 500 μg/mL) for 1 h at 32 °C. The results showed for CA, BA, BB and SY a dose dependent increase in tail DNA%, tail length and tail moment in human sperm when compared to control group. When control values were compared in the studied parameters in the treatment concentrations, SY was found to exhibit the highest level of DNA damage followed by BB > BA > CA. However, none of the food additives affected the tail DNA%, tail length and tail moment at 50 and 100 μg/mL. At 200 μg/mL of SY, the tail DNA% and tail length of sperm were 95.80 ± 0.28 and 42.56 ± 4.66, for BB the values were 95.06 ± 2.30 and 39.56 ± 3.78, whereas for BA the values were 89.05 ± 2.78 and 31.50 ± 0.71, for CA the values were 88.59 ± 6.45 and 13.59 ± 2.74, respectively. However, only the highest concentration of the used food additives significantly affected the studied parameters of sperm DNA. The present results indicate that SY and BB are more harmful than BA and CA to human sperm in vitro.

  17. circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica.

    Science.gov (United States)

    Cao, Zhouli; Xiao, Qingling; Dai, Xiaoniu; Zhou, Zewei; Jiang, Rong; Cheng, Yusi; Yang, Xiyue; Guo, Huifang; Wang, Jing; Xi, Zhaoqing; Yao, Honghong; Chao, Jie

    2017-12-13

    Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO 2 -induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO 2 on protein production and functional changes in pulmonary fibroblasts have been less extensively studied. Sigma-1 receptor, which has been associated with cell proliferation and migration in the central nervous system, is expressed in the lung, but its role in silicosis remains unknown. To elucidate the role of sigma-1 receptor in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Both molecular biological assays and pharmacological techniques, combined with functional experiments, such as migration and proliferation, were applied in human pulmonary fibroblasts from adults to analyze the molecular and functional changes induced by SiO 2 . SiO 2 induced endoplasmic reticulum stress in association with enhanced expression of sigma-1 receptor. Endoplasmic reticulum stress promoted migration and proliferation of human pulmonary fibroblasts-adult exposed to SiO 2 , inducing the development of silicosis. Inhibition of sigma-1 receptor ameliorated endoplasmic reticulum stress and fibroblast functional changes induced by SiO 2 . circHIPK2 is involved in the regulation of sigma-1 receptor in human pulmonary fibroblasts-adult exposed to SiO 2 . Our study elucidated a link between SiO 2 -induced fibrosis and sigma-1 receptor signaling, thereby providing novel insight into the potential use of sigma-1 receptor/endoplasmic reticulum stress in the development of novel therapeutic strategies for silicosis treatment.

  18. Mathematical Models for the Apparent Mass of the Seated Human Body Exposed to Vertical Vibration

    Science.gov (United States)

    Wei, L.; Griffin, M. J.

    1998-05-01

    Alternative mathematical models of the vertical apparent mass of the seated human body are developed. The optimum parameters of four models (two single-degree-of-freedom models and two two-degree-of-freedom models) are derived from the mean measured apparent masses of 60 subjects (24 men, 24 women, 12 children) previously reported. The best fits were obtained by fitting the phase data with single-degree-of-freedom and two-degree-of-freedom models having rigid support structures. For these two models, curve fitting was performed on each of the 60 subjects (so as to obtain optimum model parameters for each subject), for the averages of each of the three groups of subjects, and for the entire group of subjects. The values obtained are tabulated. Use of a two-degree-of-freedom model provided a better fit to the phase of the apparent mass at frequencies greater than about 8 Hz and an improved fit to the modulus of the apparent mass at frequencies around 5 Hz. It is concluded that the two-degree-of-freedom model provides an apparent mass similar to that of the human body, but this does not imply that the body moves in the same manner as the masses in this optimized two-degree-of-freedom model.

  19. Chronic and acute risk assessment of human exposed to novaluron-bifenthrin mixture in cabbage.

    Science.gov (United States)

    Shi, Kaiwei; Li, Li; Li, Wei; Yuan, Longfei; Liu, Fengmao

    2016-09-01

    Based on the dissipation and residual level in cabbage determined by gas chromatography coupled with an electron capture detector (GC-ECD), chronic and acute risk assessments of the novaluron and bifenthrin were investigated. At different spiked levels, mean recoveries were between 81 and 108 % with relative standard deviations (RSDs) from 1.1 to 6.8 %. The limit of quantification (LOQ) was 0.01 mg kg(-1), and good linearity with correlation coefficient (>0.9997) were obtained. The half-lives of novaluron and bifenthrin in cabbage were in the range of 3.2~10 days. Based on the consumption data in China, the risk quotients (RQs) of novaluron and bifenthrin were all below 100 %. The chronic and acute risk of novaluron in cabbage was relatively low, while bifenthrin exerts higher acute risk to humans than chronic risk. The obtained results indicated that the use of novaluron-bifenthrin mixture does not seem to pose any chronic or acute risk to humans even if cabbages are consumed at high application dosages and short preharvest interval (PHI).

  20. DNA damage in human lymphocytes exposed to four food additives in vitro.

    Science.gov (United States)

    Yilmaz, Serkan; Unal, Fatma; Yüzbaşıoğlu, Deniz; Celik, Mustafa

    2014-11-01

    In vitro genotoxic effects of antioxidant additives, such as citric acid (CA) and phosphoric acid (PA) and their combination, as well as antimicrobial additives, such as benzoic acid (BA) and calcium propionate (CP), on human lymphocytes were determined using alkaline single-cell gel electrophoresis. There was a significant increase in the DNA damage in human lymphocytes after 1 h of in vitro exposure to CA, PA, BA and CP (200, 25-200, 50-500, 50-1000 μg/mL, respectively). The combination of CA and PA significantly increased the mean tail intensity at all the concentrations used (25-200 μg/mL) and significantly increased the mean tail length mainly after higher concentrations (100 and 200 μg/mL). Data in this study showed that the concentrations of food additives used induce DNA damage and PA was the most genotoxic and CA was less genotoxic additives among them. © The Author(s) 2012.

  1. Cigarette Smoke-Exposed Candida albicans Increased Chitin Production and Modulated Human Fibroblast Cell Responses

    Directory of Open Access Journals (Sweden)

    Humidah Alanazi

    2014-01-01

    Full Text Available The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P<0.01 sensitive to oxidation but significantly (P<0.01 resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P<0.01 slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers.

  2. Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

    International Nuclear Information System (INIS)

    Lundby, Carsten; Pilegaard, Henriette; Hall, Gerrit van; Sander, Mikael; Calbet, Jose; Loft, Steffen; Moeller, Peter

    2003-01-01

    Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle biopsies from seven healthy humans were obtained at sea level and after 2 and 8 weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by quantitative RT-PCR of mRNA levels did not significantly change during high-altitude hypoxia, although the data could not exclude a minor upregulation. The expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite increased generation of oxidative DNA damage

  3. DNA damage in cultured human skin fibroblasts exposed to excimer laser radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rimoldi, D.; Miller, A.C.; Freeman, S.E.; Samid, D. (Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD (USA))

    1991-06-01

    Ultraviolet excimer lasers are being considered for use in a variety of refractive and therapeutic procedures, the long-term biologic consequences of which are unknown. The effect of sublethal doses of 193-nm laser radiation on cellular DNA was examined in cultured human skin fibroblasts. In contrast to 248 nm, treatments with the 193-nm laser radiation below 70 J/m2 did not cause significant pyrimidine dimer formation in the skin cells. This was indicated by the lack of excision repair activities (unscheduled DNA synthesis assay), and further demonstrated by direct analysis of pyrimidine dimers in DNA from irradiated cells. However, a low level of unscheduled DNA synthesis could be detected following irradiation at 193 nm with 70 J/m2. Both the 193-nm and 248-nm radiation were able to induce chromosomal aberrations, as indicated by a micronucleus assay. A dose-dependent increase in micronuclei frequency was observed 48 and 72 h after laser irradiation. These results indicate that exposure of actively replicating human skin fibroblasts to sublethal doses of either 193- or 248-nm laser radiation can result in genotoxicity.

  4. Regulation of SUMO2 Target Proteins by the Proteasome in Human Cells Exposed to Replication Stress

    DEFF Research Database (Denmark)

    Bursomanno, Sara; McGouran, Joanna F; Kessler, Benedikt M

    2015-01-01

    In human cells, SUMO2 is predominantly conjugated to target proteins in response to cellular stress. Previous studies suggested that proteins conjugated to SUMO2, but not to SUMO1, could be regulated by the ubiquitin-mediated proteasome system. Hence, we set out to understand the role...... of the proteasome in determining the fate of proteins conjugated to SUMO2 when cells are treated with DNA replication stress conditions. We conducted a quantitative proteomic analysis in a U2OS cell line stably expressing SUMO2(Q87R) tagged with StrepHA in the presence or absence of epoxomicin (EPOX), a proteasome...... inhibitor. We identified subgroups of putative SUMO2 targets that were either degraded or stabilized by EPOX upon SUMO2 conjugation in response to replication stress. Interestingly, the subgroup of proteins degraded upon SUMO2 conjugation was enriched in proteins playing roles in DNA damage repair...

  5. DNA repair in human cells exposed to combinations of carcinogenic agents

    International Nuclear Information System (INIS)

    Setlow, R.B.; Ahmed, F.E.

    1980-01-01

    Normal human and XP 2 fibroblasts were treated with uv plus uv-mimetic chemicals. The uv dose used was sufficient to saturate the uv excision repair system. Excision repair after combined treatments was estimated by unscheduled DNA synthesis, BrdUrd photolysis, and the loss of sites sensitive to a uv specific endonuclease. Since the repair of damage from uv and its mimetics is coordinately controlled we expected that there would be similar rate-limiting steps in the repair of uv and chemical damage and that after a combined treatment the total amount of repair would be the same as from uv or the chemicals separately. The expectation was not fulfilled. In normal cells repair after a combined treatment was additive whereas in XP cells repair after a combined treatment was usually less than after either agent separately. The chemicals tested were AAAF, DMBA-epoxide, 4NQO, and ICR-170

  6. CYTOKINESIS-BLOCK MICRONUCLEUS ASSAY IN HUMAN GLIOMA CELLS EXPOSED TO RADIATION

    Directory of Open Access Journals (Sweden)

    Jerzy Slowinski

    2011-05-01

    Full Text Available Biological tests are efficient in reflecting the biological influences of several types of generally harmful exposures. The micronucleus assay is widely used in genotoxicity studies or studies on genomic damage in general. We present methodological aspects of cytokinesis-block micronucleus assay performed in human gliomas irradiated in vitro. Eight human glioblastoma cell lines obtained from DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Germany were gamma-irradiated (60Co over a dose range of 0-10 Gy. Cytokinesis-block micronucleus assay was performed to quantitate cytogenetic damage. The cells were fixed directly on dishes, stained with fluorochrome DAPI and evaluated under fluorescent and phase contrast microscope. The micronucleus frequency was expressed as a micronuclei (MN per binucleated cell (BNC ratio, calculated after scoring at least 100 BNC per dish. The frequency of spontaneous MN ranged from 0.17 to 0.613 (mean: 0.29 ± 0.14. After irradiation increase of MN frequency in the range of 0.312 - 2.241 (mean: 0.98 ± 0.68 was found at 10 Gy. Gliomas are extremely heterogenous in regard to cytogenetic effects of irradiation, as shown in this study by cytokinesis-block micronucleus assay. This test is easily performed on irradiated glioma cell lines and can assist in determining their radiosensitivity. However, in order to obtain reliable and reproducible results, precise criteria for MN scoring must be strictly followed. Simultaneous use of fluorescent and phase contrast equipment improves imaging of morphological details and can further optimize MN scoring.

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

    Science.gov (United States)

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

    2007-01-01

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

  8. Cytogenetic effects of irradiation in epithelial kidney cells of monkeys and possibilities of using these data for evaluation of chromosome aberration level in kidneys of persons subjected to radiotherapy

    International Nuclear Information System (INIS)

    Machavariani, M.G.

    1983-01-01

    Data on somatic mutagenesis, induced by radiation, in epithelial kidney cells of monkeys are presented. It is noted that chromosomal aberrations in the kideny cells of monkeys can be indicator of estimation of hUman kideny state during radiotherapy

  9. Expression of advanced glycation end-products on sun-exposed and non-exposed cutaneous sites during the ageing process in humans.

    Science.gov (United States)

    Crisan, Maria; Taulescu, Marian; Crisan, Diana; Cosgarea, Rodica; Parvu, Alina; Cãtoi, Cornel; Drugan, Tudor

    2013-01-01

    The glycation process is involved in both the intrinsic (individual, genetic) and extrinsic (ultraviolet light, polution and lifestyle) aging processes, and can be quantified at the epidermal or dermal level by histological, immunohistochemical (IHC), or imagistic methods. Our study is focused on a histological and immunohistological comparison of sun-protected regions versus sun-exposed regions from different age groups of skin phototype III subjects, related to the aging process. Skin samples collected from non-protected and UV protected regions of four experimental groups with different ages, were studied using histology and IHC methods for AGE-CML [N(epsilon)-(carboxymethyl)lysine]. A semi-quantitative assessment of the CML expression in the microvascular endothelium and dermal fibroblasts was performed. The Pearson one-way ANOVA was used to compare data between the groups. In the dermis of sun-exposed skin, the number and the intensity of CML positive cells in both fibroblasts and endothelial cells (p<0.05) was higher compared to sun-protected skin, and was significantly increased in older patients. The sun-exposed areas had a more than 10% higher AGE-CML score than the protected areas. No statistically significant correlation was observed between the histological score and the IHC expression of CML. We concluded that in healthy integument, the accumulation of final glycation products increases with age and is amplified by ultraviolet exposure. The study provides new knowledge on differences of AGE-CML between age groups and protected and unprotected areas and emphasizes that endothelium and perivascular area are most affected, justifying combined topical and systemic therapies.

  10. Expression of advanced glycation end-products on sun-exposed and non-exposed cutaneous sites during the ageing process in humans.

    Directory of Open Access Journals (Sweden)

    Maria Crisan

    Full Text Available The glycation process is involved in both the intrinsic (individual, genetic and extrinsic (ultraviolet light, polution and lifestyle aging processes, and can be quantified at the epidermal or dermal level by histological, immunohistochemical (IHC, or imagistic methods. Our study is focused on a histological and immunohistological comparison of sun-protected regions versus sun-exposed regions from different age groups of skin phototype III subjects, related to the aging process. Skin samples collected from non-protected and UV protected regions of four experimental groups with different ages, were studied using histology and IHC methods for AGE-CML [N(epsilon-(carboxymethyllysine]. A semi-quantitative assessment of the CML expression in the microvascular endothelium and dermal fibroblasts was performed. The Pearson one-way ANOVA was used to compare data between the groups. In the dermis of sun-exposed skin, the number and the intensity of CML positive cells in both fibroblasts and endothelial cells (p<0.05 was higher compared to sun-protected skin, and was significantly increased in older patients. The sun-exposed areas had a more than 10% higher AGE-CML score than the protected areas. No statistically significant correlation was observed between the histological score and the IHC expression of CML. We concluded that in healthy integument, the accumulation of final glycation products increases with age and is amplified by ultraviolet exposure. The study provides new knowledge on differences of AGE-CML between age groups and protected and unprotected areas and emphasizes that endothelium and perivascular area are most affected, justifying combined topical and systemic therapies.

  11. Clastogenic effects in human lymphocytes exposed to low and high dose rate X-ray irradiation and vitamin C

    International Nuclear Information System (INIS)

    Konopacka, M; Rogolinski, J.

    2011-01-01

    In the present work we investigated the ability of vitamin C to modulate clastogenic effects induced in cultured human lymphocytes by X-irradiation delivered at either high (1 Gy/min) or low dose rate (0.24 Gy/min). Biological effects of the irradiation were estimated by cytokinesis-block micronucleus assay including the analysis of the frequency of micronuclei (MN) and apoptotic cells as well as calculation of nuclear division index (NDI). The numbers of micronucleated binucleate lymphocytes (MN-CBL) were 24.85 ± 2.67% and 32.56 ± 3.17% in cultures exposed to X-rays (2 Gy) delivered at low and high dose rates, respectively. Addition of vitamin C (1-20 μg/ml) to the medium of cultures irradiated with the low dose rate reduced the frequency of micronucleated lymphocytes with multiple MN in a concentration-dependent manner. Lymphocytes exposed to the high dose rate radiation showed a U-shape response: low concentration of vitamin C significantly reduced the number of MN, whereas high concentration influenced the radiation-induced total number of micronucleated cells insignificantly, although it increased the number of cells with multiple MN. Addition of vitamin C significantly reduced the fraction of apoptotic cells, irrespective of the X-ray dose rate. These results indicate that radiation dose rate is an important exposure factor, not only in terms of biological cell response to irradiation, but also with respect to the modulating effects of antioxidants. (authors)

  12. Osteoblastic differentiation and stress response of human mesenchymal stem cells exposed to alternating current electric fields

    Directory of Open Access Journals (Sweden)

    Kaplan David L

    2011-01-01

    Full Text Available Abstract Background Electric fields are integral to many biological events, from maintaining cellular homeostasis to embryonic development to healing. The application of electric fields offers substantial therapeutic potential, while optimal dosing regimens and the underlying mechanisms responsible for the positive clinical impact are poorly understood. Methods The purpose of this study was to track the differentiation profile and stress response of human bone marrow derived mesenchymal stem cells (hMSCs undergoing osteogenic differentiation during exposure to a 20 mV/cm, 60 kHz electric field. Morphological and biochemical changes were imaged using endogenous two-photon excited fluorescence (TPEF and quantitatively assessed through eccentricity calculations and extraction of the redox ratio from NADH, FAD and lipofuscin contributions. Real time reverse transcriptase-polymerase chain reactions (RT-PCR were used to track osteogenic differentiation markers, namely alkaline phosphatase (ALP and collagen type 1 (col1, and stress response markers, such as heat shock protein 27 (hsp27 and heat shock protein 70 (hsp70. Comparisons of collagen deposition between the stimulated hMSCs and controls were examined through second harmonic generation (SHG imaging. Results Quantitative differences in cell morphology, as described through an eccentricity ratio, were found on days 2 and days 5 (p Conclusions Electrical stimulation is a useful tool to improve hMSC osteogenic differentiation, while heat shock proteins may reveal underlying mechanisms, and optical non-invasive imaging may be used to monitor the induced morphological and biochemical changes.

  13. In vitro safety evaluation of human nasal epithelial cell monolayers exposed to carrageenan sinus wash.

    Science.gov (United States)

    Ramezanpour, Mahnaz; Murphy, Jae; Smith, Jason L P; Vreugde, Sarah; Psaltis, Alkis James

    2017-12-01

    Carrageenans have shown to reduce the viral load in nasal secretions and lower the incidence of secondary infections in children with common cold. Despite the widespread use of carrageenans in topical applications, the effect of carrageenans on the sinonasal epithelial barrier has not been elucidated. We investigate the effect of different carrageenans on the sinonasal epithelial barrier and inflammatory response in vitro. Iota and Kappa carrageenan delivered in saline irrigation solutions applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells from chronic rhinosinusitis patients and controls. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER) and immunolocalization of F actin. Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied. Kappa or Iota carrageenan in the different solutions was not toxic, did not have detrimental effects on epithelial barrier structure and CBF. Rather, application of Kappa carrageenan significantly increased TEER and suppressed interleukin 6 (IL-6) secretion in ALI cultures from CRS patients. Kappa or Iota carrageenan solution was safe and did not negatively affect epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6 production in CRS patients, indicating positive effects on epithelial barrier function in vitro. © 2017 ARS-AAOA, LLC.

  14. Hearing Loss in Perinatally Human Immunodeficiency Virus-Infected and Human Immunodeficiency Virus -Exposed but Uninfected Children and Adolescents

    Science.gov (United States)

    Torre, Peter; Zeldow, Bret; Hoffman, Howard J.; Buchanan, Ashley; Siberry, George K.; Rice, Mabel; Sirois, Patricia A.; Williams, Paige L.

    2012-01-01

    Background Little is known about hearing loss in children with HIV infection (HIV+). We examined the prevalence of hearing loss in perinatally HIV+ and HIV-exposed but uninfected (HEU) children, compared these to the percentage with hearing loss in the general population, and evaluated possible risk factors for hearing loss in HIV+ and HEU children. Methods Audiometric examinations were completed in children who met any pre-specified criteria for possible hearing loss. The hearing examination consisted of a tympanogram in each ear and pure-tone air-conduction threshold testing from 500 through 4000 Hz. Hearing loss was defined as the pure-tone average over these frequencies ≥20 dB hearing level (HL). The associations of demographic, parent/caregiver, HIV disease, and HIV treatment with hearing loss were evaluated with univariate and multivariable logistic regression models. Results Hearing testing was completed in 231 children (145 HIV+ and 86 HEU). Hearing loss occurred in 20.0% of HIV+ children and 10.5% of HEU children. After adjusting for caregiver education level, HIV infection was associated with increased odds of hearing loss [adjusted odds ratio (aOR)=2.13, 95% confidence interval (CI): 0.95–4.76, p=0.07]. Among HIV+ children, those with a CDC Class C diagnosis had over twice the odds of hearing loss (aOR=2.47, 95% CI: 1.04–5.87, p=0.04). The prevalence of hearing loss was higher in both HIV+ and HEU children compared with NHANES III children. Conclusions Hearing loss was more common in both HIV+ and HEU children than in healthy children. More advanced HIV illness increased the risk of hearing loss in HIV+ children. PMID:22549437

  15. Psychophysical chromatic mechanisms in macaque monkey.

    Science.gov (United States)

    Stoughton, Cleo M; Lafer-Sousa, Rosa; Gagin, Galina; Conway, Bevil R

    2012-10-24

    Chromatic mechanisms have been studied extensively with psychophysical techniques in humans, but the number and nature of the mechanisms are still controversial. Appeals to monkey neurophysiology are often used to sort out the competing claims and to test hypotheses arising from the experiments in humans, but psychophysical chromatic mechanisms have never been assessed in monkeys. Here we address this issue by measuring color-detection thresholds in monkeys before and after chromatic adaptation, employing a standard approach used to determine chromatic mechanisms in humans. We conducted separate experiments using adaptation configured as either flickering full-field colors or heterochromatic gratings. Full-field colors would favor activity within the visual system at or before the arrival of retinal signals to V1, before the spatial transformation of color signals by the cortex. Conversely, gratings would favor activity within the cortex where neurons are often sensitive to spatial chromatic structure. Detection thresholds were selectively elevated for the colors of full-field adaptation when it modulated along either of the two cardinal chromatic axes that define cone-opponent color space [L vs M or S vs (L + M)], providing evidence for two privileged cardinal chromatic mechanisms implemented early in the visual-processing hierarchy. Adaptation with gratings produced elevated thresholds for colors of the adaptation regardless of its chromatic makeup, suggesting a cortical representation comprised of multiple higher-order mechanisms each selective for a different direction in color space. The results suggest that color is represented by two cardinal channels early in the processing hierarchy and many chromatic channels in brain regions closer to perceptual readout.

  16. Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Naylor, Paul H; Egan, James E; Berinstein, Neil L; Kast, W Martin

    2016-05-01

    Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

  17. Whole-Genome Expression Analysis of Human Mesenchymal Stromal Cells Exposed to Ultrasmooth Tantalum vs. Titanium Oxide Surfaces

    DEFF Research Database (Denmark)

    Stiehler, C.; Bunger, C.; Overall, R. W.

    2013-01-01

    to titanium (Ti) surface. The aim of this study was to extend the previous investigation of biocompatibility by monitoring temporal gene expression of MSCs on topographically comparable smooth Ta and Ti surfaces using whole-genome gene expression analysis. Total RNA samples from telomerase-immortalized human...... MSCs cultivated on plain sputter-coated surfaces of Ta or Ti for 1, 2, 4, and 8 days were hybridized to n = 16 U133 Plus 2.0 arrays (Affymetrix(A (R))). Functional annotation, cluster and pathway analyses were performed. The vast majority of genes were differentially regulated after 4 days...... of cultivation and genes upregulated by MSCs exposed to Ta and Ti were predominantly related to the processes of differentiation and transcription, respectively. Functional annotation analysis of the 1,000 temporally most significantly regulated genes suggests earlier cellular differentiation on Ta compared...

  18. Induction of SCE by DNA cross-links in human fibroblasts exposed to 8-MOP and UVA irradiation

    International Nuclear Information System (INIS)

    Bredberg, A.; Lambert, B.

    1983-01-01

    To study the SCE-inducing effect of psoralen cross-links in the DNA of normal, human fibroblasts, cell cultures were exposed to PUVA (0.2-1 μg of 8-MOP per ml, followed by UVA irradiation at 0.04 J/cm 2 ) and carefully washed to remove non-covalently bound psoralen. Some cell cultures were then given a second dose of UVA (1.1 J/cm 2 ), either immediately after PUVA or 1-3 days later. By this type of treatment, cells with different proportions of DNA cross-links are obtained. The initial PUVA treatment will mainly give rise to psoralen monoadducts and only few cross-links in the DNA, and the second UVA irradiation will convert a number of the psoralen monoadducts into cross-links. (orig./AJ)

  19. Transcriptome analysis of the human T lymphocyte cell line Jurkat and human peripheral blood mononuclear cells exposed to deoxynivalenol (DON): New mechanistic insights

    Energy Technology Data Exchange (ETDEWEB)

    Katika, Madhumohan R. [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Hendriksen, Peter J.M. [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Shao, Jia [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Loveren, Henk van [Department of Health Risk Analysis and Toxicology, Maastricht University (Netherlands); National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre (Netherlands); Peijnenburg, Ad, E-mail: ad.peijnenburg@wur.nl [RIKILT-Institute of Food Safety, Wageningen University and Research Centre, Wageningen (Netherlands); Netherlands Toxicogenomics Centre (Netherlands)

    2012-10-01

    Deoxynivalenol (DON) or vomitoxin is a commonly encountered type-B trichothecene mycotoxin, produced by Fusarium species predominantly found in cereals and grains. DON is known to exert toxic effects on the gastrointestinal, reproductive and neuroendocrine systems, and particularly on the immune system. Depending on dose and exposure time, it can either stimulate or suppress immune function. The main objective of this study was to obtain a deeper insight into DON-induced effects on lymphoid cells. For this, we exposed the human T-lymphocyte cell line Jurkat and human peripheral blood mononuclear cells (PBMCs) to various concentrations of DON for various times and examined gene expression changes by DNA microarray analysis. Jurkat cells were exposed to 0.25 and 0.5 μM DON for 3, 6 and 24 h. Biological interpretation of the microarray data indicated that DON affects various processes in these cells: It upregulates genes involved in ribosome structure and function, RNA/protein synthesis and processing, endoplasmic reticulum (ER) stress, calcium-mediated signaling, mitochondrial function, oxidative stress, the NFAT and NF-κB/TNF-α pathways, T cell activation and apoptosis. The effects of DON on the expression of genes involved in ER stress, NFAT activation and apoptosis were confirmed by qRT-PCR. Other biochemical experiments confirmed that DON activates calcium-dependent proteins such as calcineurin and M-calpain that are known to be involved in T cell activation and apoptosis. Induction of T cell activation was also confirmed by demonstrating that DON activates NFATC1 and induces its translocation from the cytoplasm to the nucleus. For the gene expression profiling of PBMCs, cells were exposed to 2 and 4 μM DON for 6 and 24 h. Comparison of the Jurkat microarray data with those obtained with PBMCs showed that most of the processes affected by DON in the Jurkat cell line were also affected in the PBMCs. -- Highlights: ► The human T cell line Jurkat and human

  20. Cytogenetic damage in human blood lymphocytes exposed in vitro and in vivo to space-relevant HZE-particles

    Science.gov (United States)

    Lee, Ryonfa; Nasonova, Elena; Sommer, Sylvester; Hartel, Carola; Ritter, Sylvia

    During space missions astronauts are exposed to cosmic radiations which are different from natural background radiation on Earth in both quantity and quality. Dose rate in space environment is at least 100 times higher than that on Earth. In addition, the natural radiation on Earth consists mainly of X-, γ-rays and α-emitters, while in space charged particles from protons to iron ions are predominant. The composition of radiation environment of outer space is well understood, however, due to a lack of data on the biological effects of dose, dose-rate and especially HZE (high charge Z and energy E) particles, large uncertainties exist in estimating the health risks for long-term space mission. To contribute to this issue, we investigated cytogenetic damage induced by heavy charged particles in human lymphocytes, since chromosome aberration yield is a biomarker showing an association with cancer risk. Lymphocytes collected from a healthy donor were irradiated with carbon ions (C-ions) in vitro with various energies (11.4 to 400 MeV/u; LET values 11 to 175 keV/µm) at either UNILAC or SIS facility (GSI, Germany) or exposed to X-rays. Additionally, peripheral blood was obtained from prostate cancer patients, treated with intensity modulated radiation therapy (IMRT) or IMRT combined with C-ion boost. Samples were taken before, during and after the radiotherapy. Chromosome samples were stained with FPG-technique to enable aberration analysis in 1st cycle metaphases. After in vitro exposure to C-ions, RBE values for the induction of chromosome aberrations increased with sampling time. The effect was most pronounced in samples exposed to 175 keV/µm C-ions and can be attributed to a pronounced cell cycle delay of heavily damaged cells. Thus, for a reliable risk assessment, the effect of selective cell cycle delay following particle exposure should be taken into account. M-FISH analysis of selected samples to assess aberration quality revealed higher frequencies of

  1. Ion transport in a human lens epithelial cell line exposed to hyposmotic and apoptotic stress.

    Science.gov (United States)

    Chimote, Ameet A; Adragna, Norma C; Lauf, Peter K

    2010-04-01

    Membrane transport changes in human lens epithelial (HLE-B3) cells under hyposmotic and apoptotic stress were compared. Cell potassium content, K(i), uptake of the K congener rubidium, Rb(i), and water content were measured after hyposmotic stress induced by hypotonicity, and apoptotic stress by the protein-kinase inhibitor staurosporine (STP). Cell water increased in hyposmotic (150 mOsm) as compared to isosmotic (300 mOsm) balanced salt solution (BSS) by >2-fold at 5 min and decreased within 15 min to baseline values accompanied by a 40% K(i) loss commensurate with cell swelling and subsequent cell shrinkage likely due to regulatory volume decrease (RVD). Loss of K(i), and accompanying water, and Rb(i) uptake in hyposmotic BSS were prevented by clotrimazole (CTZ) suggesting water shifts associated with K and Rb flux via intermediate conductance K (IK) channels, also detected at the mRNA and protein level. In contrast, 2 h after 2 microM STP exposure, the cells lost approximately 40% water and approximately 60% K(i), respectively, consistent with apoptotic volume decrease (AVD). Indeed, water and K(i) loss was at least fivefold greater after hyposmotic than after apoptotic stress. High extracellular K and 2 mM 4-aminopyridine (4-AP) but not CTZ significantly reduced apoptosis. Annexin labeling phosphatidylserine (PS) at 15 min suggested loss of lipid asymmetry. Quantitative PCR revealed significant IK channel expression during prolonged hyposmotic stress. Results suggest in HLE-B3 cells, IK channels likely partook in and were down regulated after RVD, whereas pro-apoptotic STP-activation of 4-AP-sensitive voltage-gated K channels preceded or accompanied PS externalization before subsequent apoptosis. J. Cell. Physiol. 223: 110-122, 2010. (c) 2009 Wiley-Liss, Inc.

  2. Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey Cytochrome P450 2C9, a New Efavirenz Oxidase.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-07-01

    Cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. In humans, the cytochrome P450 (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, S-mephenytoin, and diclofenac. However, comprehensive evaluation regarding substrate specificity of monkey CYP2C9 has not been conducted. In the present study, 89 commercially available drugs were examined to find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled those of human CYP2C9 or CYP2C19, with some differences in substrate specificities. Although efavirenz is known as a marker substrate for human CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14 positions. These results suggest that the efavirenz 8-oxidation could be one of the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to limited specific differences in drug oxidative metabolism between cynomolgus monkeys and humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Mitochondrial damage and cytoskeleton reorganization in human dermal fibroblasts exposed to artificial visible light similar to screen-emitted light.

    Science.gov (United States)

    Rascalou, Adeline; Lamartine, Jérôme; Poydenot, Pauline; Demarne, Frédéric; Bechetoille, Nicolas

    2018-05-05

    Artificial visible light is everywhere in modern life. Social communication confronts us with screens of all kinds, and their use is on the rise. We are therefore increasingly exposed to artificial visible light, the effects of which on skin are poorly known. The purpose of this study was to model the artificial visible light emitted by electronic devices and assess its effect on normal human fibroblasts. The spectral irradiance emitted by electronic devices was optically measured and equipment was developed to accurately reproduce such artificial visible light. Effects on normal human fibroblasts were analyzed on human genome microarray-based gene expression analysis. At cellular level, visualization and image analysis were performed on the mitochondrial network and F-actin cytoskeleton. Cell proliferation, ATP release and type I procollagen secretion were also measured. We developed a device consisting of 36 LEDs simultaneously emitting blue, green and red light at distinct wavelengths (450 nm, 525 nm and 625 nm) with narrow spectra and equivalent radiant power for the three colors. A dose of 99 J/cm 2 artificial visible light was selected so as not to induce cell mortality following exposure. Microarray analysis revealed 2984 light-modulated transcripts. Functional annotation of light-responsive genes revealed several enriched functions including, amongst others, the "mitochondria" and "integrin signaling" categories. Selected results were confirmed by real-time quantitative PCR, analyzing 24 genes representing these two categories. Analysis of micro-patterned culture plates showed marked fragmentation of the mitochondrial network and disorganization of the F-actin cytoskeleton following exposure. Functionally, there was considerable impairment of cell growth and spread, ATP release and type I procollagen secretion in exposed fibroblasts. Artificial visible light induces drastic molecular and cellular changes in normal human fibroblasts. This may impede

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

    Beran, Michael J

    2016-03-01

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

  6. Mortality of monkeys after exposure to fission neutrons and the effects of autologous bone marrow transplantation

    International Nuclear Information System (INIS)

    Broerse, J.J.; Bekkum, D.W. van; Hollander, C.F.; Davids, J.A.G.

    1978-01-01

    In order to assess the risk of exposure to ionizing radiation in man, and to evaluate the results of therapeutic measures, the mortality of rhesus monkeys irradiated with X-rays and fission neutrons and the effect of autologous bone marrow transplantation have been investigated. The LDsub(50/30d) values for X- and neutron-irradiated monkeys amount to 525 and 260 rad respectively, resulting in an r.b.e. of approximately 2 for the occurrence of the bone marrow syndrome. Protection of the animals by autologous bone marrow transplantation was observed up to doses of 860 rad of X-rays and 440 rad of fission neutrons. After both fission-neutron irradiation and X-irradiation in the lowest range of lethal doses, the bone marrow syndrome was found to occur without the concurrent incidence of the intestinal syndrome. The studies indicate that, for humans accidentally exposed to what would otherwise be lethal doses of fast neutrons, bone marrow transplantation may be beneficial. (author)

  7. Call Combinations in Monkeys: Compositional or Idiomatic Expressions?

    Science.gov (United States)

    Arnold, Kate; Zuberbuhler, Klaus

    2012-01-01

    Syntax is widely considered the feature that most decisively sets human language apart from other natural communication systems. Animal vocalisations are generally considered to be holistic with few examples of utterances meaning something other than the sum of their parts. Previously, we have shown that male putty-nosed monkeys produce call…

  8. Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

    International Nuclear Information System (INIS)

    Tal, Tamara L.; Simmons, Steven O.; Silbajoris, Robert; Dailey, Lisa; Cho, Seung-Hyun; Ramabhadran, Ram; Linak, William; Reed, William; Bromberg, Philip A.; Samet, James M.

    2010-01-01

    Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

  9. Nature of the Refractive Errors in Rhesus Monkeys (Macaca mulatta) with Experimentally Induced Ametropias

    Science.gov (United States)

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

    2010-01-01

    We analyzed the contribution of individual ocular components to vision-induced ametropias in 210 rhesus monkeys. The primary contribution to refractive-error development came from vitreous chamber depth; a minor contribution from corneal power was also detected. However, there was no systematic relationship between refractive error and anterior chamber depth or between refractive error and any crystalline lens parameter. Our results are in good agreement with previous studies in humans, suggesting that the refractive errors commonly observed in humans are created by vision-dependent mechanisms that are similar to those operating in monkeys. This concordance emphasizes the applicability of rhesus monkeys in refractive-error studies. PMID:20600237

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  12. Lack of Exposure in a First-in-Man Study Due to Aldehyde Oxidase Metabolism: Investigated by Use of 14C-microdose, Humanized Mice, Monkey Pharmacokinetics, and In Vitro Methods.

    Science.gov (United States)

    Jensen, Klaus Gjervig; Jacobsen, Anne-Marie; Bundgaard, Christoffer; Nilausen, Dorrit Østergaard; Thale, Zia; Chandrasena, Gamini; Jørgensen, Martin

    2017-01-01

    Inclusion of a microdose of 14 C-labeled drug in the first-in-man study of new investigational drugs and subsequent analysis by accelerator mass spectrometry has become an integrated part of drug development at Lundbeck. It has been found to be highly informative with regard to investigations of the routes and rates of excretion of the drug and the human metabolite profiles according to metabolites in safety testing guidance and also when additional metabolism-related issues needed to be addressed. In the first-in-man study with the NCE Lu AF09535, contrary to anticipated, surprisingly low exposure was observed when measuring the parent compound using conventional bioanalysis. Parallel accelerator mass spectrometry analysis revealed that the low exposure was almost exclusively attributable to extensive metabolism. The metabolism observed in humans was mediated via a human specific metabolic pathway, whereas an equivalent extent of metabolism was not observed in preclinical species. In vitro, incubation studies in human liver cytosol revealed involvement of aldehyde oxidase (AO) in the biotransformation of Lu AF09535. In vivo, substantially lower plasma exposure of Lu AF09535 was observed in chimeric mice with humanized livers compared with control animals. In addition, Lu AF09535 exhibited very low oral bioavailability in monkeys despite relatively low clearance after intravenous administration in contrast to the pharmacokinetics in rats and dogs, both showing low clearance and high bioavailability. The in vitro and in vivo methods applied were proved useful for identifying and evaluating AO-dependent metabolism. Different strategies to integrate these methods for prediction of in vivo human clearance of AO substrates were evaluated. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Quercetin Protects Primary Human Osteoblasts Exposed to Cigarette Smoke through Activation of the Antioxidative Enzymes HO-1 and SOD-1

    Directory of Open Access Journals (Sweden)

    Karl F. Braun

    2011-01-01

    Full Text Available Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS. The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO- 1 and superoxide-dismutase- (SOD- 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers.

  14. Epidurography with metrizamide in Rhesus monkeys

    International Nuclear Information System (INIS)

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

    1980-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  17. Evaluation of Genotoxic and Cytotoxic Effects in Human Peripheral Blood Lymphocytes Exposed In Vitro to Neonicotinoid Insecticides News

    Directory of Open Access Journals (Sweden)

    María Elena Calderón-Segura

    2012-01-01

    Full Text Available Calypso (thiacloprid, Poncho (clothianidin, Gaucho (imidacloprid, and Jade (imidacloprid are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL were exposed in vitro to different concentrations of the four insecticides. The genotoxic and cytotoxic effects were evaluated using the alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated using two genotoxicity parameters: tail length and comet frequency. Exposure to 9.5×10-6 to 5.7×10-5 M Jade; 2.8×10-4 to 1.7×10-3 M Gaucho; 0.6×10-1 to 1.4×10-1 M Calypso; 1.2×10-1 to 9.5×10-1 M Poncho for 2 h induced a significant increase DNA damage with a concentration-dependent relationship. Jade was the most genotoxic of the four insecticides studied. Cytotoxicity was observed in cells exposed to 18×10-3 M Jade, 2.0×10-3 M Gaucho, 2.0×10-1 M Calypso, 1.07 M Poncho, and cell death occurred at 30×10-3 M Jade, 3.3×10-3 M Gaucho, 2.8×10-1 M Calypso, and 1.42 M Poncho. This study provides the first report of genotoxic and cytotoxic effects in PBL following in vitro exposure to commercial neonicotinoid insecticides.

  18. Hsp 70 and 90 proteins as bio indicators of stress and protein damage in human lymphocytes exposed to neutrons

    International Nuclear Information System (INIS)

    Delgado, C. E.; Letechipia de L, C.; Vega C, H. R.; Sanchez R, S. H.

    2016-09-01

    Neutrons, when interacting with the cells of the body produce free radicals, so that exposure to high doses of ionizing radiation can cause different damage to the body that can cause cell death, therefore, these effects will depend on the amount of dose, time and individual factors such as gender, age, health status and nutrition. Therefore, knowledge of cellular responses to radiation exposure is critical for developing predictive markers useful for assessing people's exposure to radiation. The purpose of this study was to estimate the cellular protein damage through the Hsp 70 and 90 proteins exposed to neutrons in human lymphocytes from clinically healthy subjects. The cell tissue was obtained by venipuncture, the lymphocytes were separated by Ficoll-Paque concentration gradient, the experimental batches were formed, thus having 5 duplicate samples, subjected to neutron irradiation in a "2"4"2Am-Be at doses of 0.25, 0.50, 0.75, 1 and 1.25 μGy at three distances 20, 21.5 and 23 cm. As a positive control, a sample exposed to heat (40 degrees Celsius) was used for 40 min. The proteins of the experimental batch were analyzed by Western-Blot and protein quantification was analyzed by densitometry, on the other hand the oxidative stress was quantified by Oxi-Blot. Was found that the neutrons at doses of 0.25 and 0.5 μGy over expressed the Hsp-70 proteins, but for Hsp-90 no over-dose expressed, there was no protein damage at the exposure doses that were established. It can be estimated that Hsp-70 proteins can serve as bio indicators of cell stress by exposure doses of 0.25 and 0.5 μGy of neutrons. (Author)

  19. Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin

    International Nuclear Information System (INIS)

    Reinhardt, P.; Cybulski, M.; Miller, S.M.; Ferrarotto, C.; Wilkins, R.; Deslauriers, Y.

    2006-01-01

    The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger the release of proinflammatory cytokines. The present study measured the ability of sunscreens to prevent cytokine secretion in human keratinocytes following cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or norfloxacin (NOR), exposed to 15 J/cm 2 UVA, and incubated for 24 h. NOR, owing to the absence of a fluorine atom in position 8, was non-phototoxic and used as a negative control. Cell viability and the release of 3 cytokines were assessed, namely interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). The measurement of these cytokines may be a useful tool for detecting photoreactive compounds. To measure their ability to prevent cytokine secretion, various sunscreens were inserted between the UVA source and the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells. LOM plus UVA, however, had an effect on cell viability and on cytokine secretion. IL-1α levels increased with LOM concentration. The release of TNF-α and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 μmol/L and decreased at higher concentrations. Sunscreens protected the cells from the effects of LOM plus UVA, as cell viability and levels of cytokines remained the same as in the control cells. In conclusion, the application of broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent phototoxic reactions initiated by drugs such as LOM. (author)

  20. Reversal of Human Papillomavirus-Specific T Cell Immune Suppression through TLR Agonist Treatment of Langerhans Cells Exposed to Human Papillomavirus Type 161

    Science.gov (United States)

    Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin

    2009-01-01

    Human papillomavirus (HPV) type 16 infects the epithelial layer of cervical mucosa and is causally associated with the generation of cervical cancer. Langerhans cells (LC) are the resident antigen-presenting cells at the site of infection and therefore are responsible for initiating an immune response against HPV16. On the contrary, LC exposed to HPV16 do not induce a specific T cell immune response, which leads to the immune evasion of HPV16. Demonstrating that Toll-like receptor 7 (TLR7) and TLR8 are expressed on human LC, we hypothesized that imidazoquinolines would activate LC exposed to HPV16, leading to the induction of an HPV16-specific cell-mediated immune response. Surprisingly both phenotypic and functional hallmarks of activation are not observed when LC are exposed to HPV16 virus-like particles (VLP) and treated with imiquimod (TLR7 agonist). However, we found that LC are activated by 3M-002 (TLR8 agonist) and resiquimod (TLR8/7 agonist). LC exposed to HPV16 VLP and subsequently treated with 3M-002 or resiquimod highly up-regulate surface activation markers, secrete pro-inflammatory cytokines and chemokines, induce CCL21-directed migration, and initiate an HPV16-specific CD8+ T cell response. These data strongly indicate that 3M-002 and resiquimod are promising therapeutics for treatment of HPV-infections and HPV-induced cervical lesions. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third

  1. Get the Monkey off Your Back

    Science.gov (United States)

    Ciabattini, David; Custer, Timothy J.

    2008-01-01

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

  2. Induction of anchorage-independent growth in primary human cells exposed to protons or HZE ions separately or in dual exposures.

    Science.gov (United States)

    Sutherland, B M; Cuomo, N C; Bennett, P V

    2005-10-01

    Travelers on space missions will be exposed to a complex radiation environment that includes protons and heavy charged particles. Since protons are present at much higher levels than are heavy ions, the most likely scenario for cellular radiation exposure will be proton exposure followed by a hit by a heavy ion. Although the effects of individual ion species on human cells are being investigated extensively, little is known about the effects of exposure to both radiation types. One useful measure of mammalian cell damage is induction of the ability to grow in a semi-solid agar medium highly inhibitory to the growth of normal human cells, termed neoplastic transformation. Using primary human cells, we evaluated induction of soft-agar growth and survival of cells exposed to protons only or to heavy charged particles (600 MeV/nucleon silicon) only as well as of cells exposed to protons followed after a 4-day interval by silicon ions. Both ions alone efficiently transformed the human cells to anchorage-independent growth. Initial experiments indicate that the dose responses for neoplastic transformation of cells exposed to protons and then after 4 days to silicon ions appear similar to that of cells exposed to silicon ions alone.

  3. Marmoset monkeys evaluate third-party reciprocity.

    Science.gov (United States)

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

    2014-05-01

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

  4. Stable Human Hepatoma Cell Lines for Efficient Regulated Expression of Nucleoside/Nucleotide Analog Resistant and Vaccine Escape Hepatitis B Virus Variants and Woolly Monkey Hepatitis B Virus.

    Directory of Open Access Journals (Sweden)

    Xin Cheng

    Full Text Available Hepatitis B virus (HBV causes acute and chronic hepatitis B (CHB. Due to its error-prone replication via reverse transcription, HBV can rapidly evolve variants that escape vaccination and/or become resistant to CHB treatment with nucleoside/nucleotide analogs (NAs. This is particularly problematic for the first generation NAs lamivudine and adefovir. Though now superseded by more potent NAs, both are still widely used. Furthermore, resistance against the older NAs can contribute to cross-resistance against more advanced NAs. For lack of feasible HBV infection systems, the biology of such variants is not well understood. From the recent discovery of Na+-taurocholate cotransporting polypeptide (NTCP as an HBV receptor new in vitro infection systems are emerging, yet access to the required large amounts of virions, in particular variants, remains a limiting factor. Stably HBV producing cell lines address both issues by allowing to study intracellular viral replication and as a permanent source of defined virions. Accordingly, we generated a panel of new tetracycline regulated TetOFF HepG2 hepatoma cell lines which produce six lamivudine and adefovir resistance-associated and two vaccine escape variants of HBV as well as the model virus woolly monkey HBV (WMHBV. The cell line-borne viruses reproduced the expected NA resistance profiles and all were equally sensitive against a non-NA drug. The new cell lines should be valuable to investigate under standardized conditions HBV resistance and cross-resistance. With titers of secreted virions reaching >3 x 10(7 viral genome equivalents per ml they should also facilitate exploitation of the new in vitro infection systems.

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

    Directory of Open Access Journals (Sweden)

    Chenggu Cai

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Two distinct gamma-2 herpesviruses in African green monkeys: a second gamma-2 herpesvirus lineage among old world primates?

    NARCIS (Netherlands)

    Greensill, J.; Sheldon, J. A.; Renwick, N. M.; Beer, B. E.; Norley, S.; Goudsmit, J.; Schulz, T. F.

    2000-01-01

    Primate gamma-2 herpesviruses (rhadinoviruses) have so far been found in humans (Kaposi's sarcoma-associated herpesvirus [KSHV], also called human herpesvirus 8), macaques (Macaca spp.) (rhesus rhadinovirus [RRV] and retroperitoneal fibromatosis herpesvirus [RFHV]), squirrel monkeys (Saimiri

  9. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to 60Co at single fraction

    International Nuclear Information System (INIS)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de; Leite, M.F.; Goes, A.M.

    2005-01-01

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to 60 Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min -1 rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by 60 Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  10. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to {sup 60}Co at single fraction

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear]. E-mail: lidia.andrade@unifenas.br; Leite, M.F. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Fisiologia e Biofisica; Goes, A.M. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia

    2005-10-15

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to {sup 60} Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min{sup -1} rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by {sup 60} Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  11. Redox proteomic evaluation of oxidative modification and recovery in a 3D reconstituted human skin tissue model exposed to UVB.

    Science.gov (United States)

    Dyer, J M; Haines, S R; Thomas, A; Wang, W; Walls, R J; Clerens, S; Harland, D P

    2017-04-01

    Exposure to UV in humans resulting in sunburn triggers a complex series of events that are a mix of immediate and delayed damage mediation and healing. While studies on the effects of UV exposure on DNA damage and repair have been reported, changes in the oxidative modification of skin proteins are poorly understood at the molecular level, despite the important role played by structural proteins in skin tissue, and the effect of the integrity of these proteins on skin appearance and health. Proteomic molecular mapping of oxidation was here applied to try to enhance understanding of skin damage and recovery from oxidative damage and UVB exposure. A redox proteomic-based approach was applied to evaluating skin protein modification when exposed to varying doses of UVB after initial oxidative stress, via tracking changes in protein oxidation during the healing process in vitro using a full-thickness reconstituted human skin tissue model. Bioassays and structural evaluation confirmed that our cultured skin tissues underwent a normal physiological response to UVB exposure. A set of potential skin marker peptides was generated, for use in tracking skin protein oxidative modification. Exposure to UVB after thermal oxidative stress was found to result in higher levels of skin protein oxidation than a non-irradiated control for up to seven days after exposure. Recovery of the skin proteins from oxidative stress, as assessed by the overall protein oxidation levels, was found to be impaired by UVB exposure. Oxidative modification was largely observed in skin structural proteins. Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin proteins, with higher exposure levels leading to increasingly impaired recovery from this damage. This has potential implications for the functional performance of the proteins and inter-related skin health and cosmetic appearance. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  12. Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen.

    Science.gov (United States)

    Abos Gracia, Beatriz; López Relaño, Juan; Revilla, Ana; Castro, Lourdes; Villalba, Mayte; Martín Adrados, Beatriz; Regueiro, Jose Ramon; Fernández-Malavé, Edgar; Martínez Naves, Eduardo; Gómez Del Moral, Manuel

    2017-01-01

    Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study was to analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA. Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ. Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses. © 2017 S. Karger AG, Basel.

  13. Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

    Science.gov (United States)

    Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

    2011-05-01

    The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

  14. Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation

    Science.gov (United States)

    Allen, Christian Harry; Kumar, Achint; Qutob, Sami; Nyiri, Balazs; Chauhan, Vinita; Murugkar, Sangeeta

    2018-01-01

    Recent findings in populations exposed to ionizing radiation (IR) indicate dose-related lens opacification occurs at much lower doses (micro-spectroscopy was used to investigate the effects of varying doses of radiation, ranging from 0.01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 h post-irradiation. Raman spectra were acquired from the nucleus and cytoplasm of the HLE cells. Spectra were collected from points in a 3  ×  3 grid pattern and then averaged. The raw spectra were preprocessed and principal component analysis followed by linear discriminant analysis was used to discriminate between dose and control for 0.25, 0.5, 2, and 5 Gy. Using leave-one-out cross-validation accuracies of greater than 74% were attained for each dose/control combination. The ultra-low doses 0.01 and 0.05 Gy were included in an analysis of band intensities for Raman bands found to be significant in the linear discrimination, and an induced repair model survival curve was fit to a band-difference-ratio plot of this data, suggesting HLE cells undergo a nonlinear response to low-doses of IR. A survival curve was also fit to clonogenic assay data done on the irradiated HLE cells, showing a similar nonlinear response.

  15. Morphofunctional evaluation of human skin preserved in glycerol and exposed to gamma radiation: a study in athymic mice

    International Nuclear Information System (INIS)

    Bringel, Fabiana de Andrade

    2011-01-01

    Extensive skin lesions expose the body to damaging agents, which makes spontaneous regeneration difficult and, in many cases, leads patient to death. In such cases, if there are no donating areas for autograft, allografts can be used. In this type of graft, tissue is processed in tissue banks, where it can be subjected to radiosterilization. According to in vitro studies, gamma radiation, in doses higher than 25 kGy, induces alterations in skin preserved in glycerol at 85%, reducing the tensile strength of irradiated tissue. Clinical observation also suggests faster integration of such graft with the receptors tissue. In order to assess if the alterations observed in vitro, would compromise in vivo use, transplants of human tissue, irradiated or not, were performed in Nude mice. The skin of the mice was subjected to macroscopic analysis, optical coherence tomography imaging, histological and biomechanical assays. It was possible to conclude that grafts irradiated with 25 kGy promoted greater initial contraction, without alteration of the final dimensions of the repair area, also displaying a faster closing of the wound. Moreover, the use of irradiated grafts (25 and 50 kGy) enabled the formation of a more organized healing process without significant effects on biomechanical properties. (author)

  16. Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound.

    Science.gov (United States)

    Gruber, Matthew J; Bader, Kenneth B; Holland, Christy K

    2014-02-01

    Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity(®)) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 ± 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

  17. Genomic Profiling of a Human Leukemic Monocytic Cell-Line (THP-1 Exposed to Alpha Particle Radiation

    Directory of Open Access Journals (Sweden)

    Vinita Chauhan

    2012-01-01

    Full Text Available This study examined alpha (α- particle radiation effects on global changes in gene expression in human leukemic monocytic cells (THP-1 for the purposes of mining for candidate biomarkers that could be used for the development of a biological assessment tool. THP-1 cells were exposed to α-particle radiation at a dose range of 0 to 1.5 Gy. Twenty-four hours and three days after exposure gene expression was monitored using microarray technology. A total of 16 genes were dose responsive and classified as early onset due to their expression 24 h after exposure. Forty-eight transcripts were dose responsive and classified as late-onset as they were expressed 72 h after exposure. Among these genes, 6 genes were time and dose responsive and validated further using alternate technology. These transcripts were upregulated and associated with biological processes related to immune function, organelle stability and cell signalling/communication. This panel of genes merits further validation to determine if they are strong candidate biomarkers indicative of α-particle exposure.

  18. Metabolism of Lutein and Zeaxanthin in Rhesus Monkeys: Identification of (3R,6′R)- and (3R,6′S)-3′-Dehydro-lutein as Common Metabolites and Comparison to Humans

    Science.gov (United States)

    Albert, Gesa I.; Hoeller, Ulrich; Schierle, Joseph; Neuringer, Martha; Johnson, Elizabeth J.; Schalch, Wolfgang

    2012-01-01

    Lutein and zeaxanthin are xanthophylls that can be found highly concentrated in the macula of the retina. They are thought to protect the macula through their role as blue-light filters and because of their antioxidant and singlet oxygen quenching properties. Examination of metabolites unique to lutein and zeaxanthin such as 3′-dehydro-lutein, and of their stereochemistry may provide insight to the mechanism by which they are formed and by which they exert protection. To evaluate the formation of such metabolites, eleven monkeys were raised on a xanthophyll-free diet, and supplemented with pure lutein or pure zeaxanthin (2.2 mg/kg body weight/d). The period of supplementation ranged between 12 to 92 weeks. At study start and throughout the study, serum samples were taken and analyzed for xanthophylls using different HPLC systems. Xanthophyll metabolites were identified using UV/VIS and HR-MS detection. Lutein and zeaxanthin metabolites were found in detectable amounts with 3′-dehydro-lutein being a common metabolite of both. Using chiral-phase HPLC, two diastereomers, (3R,6′R)-3′-dehydro-lutein and (3R,6′S)-3′-dehydro-lutein, were identified and shown to be present in nearly equimolar amounts. A pathway for their formation from either lutein or zeaxanthin is proposed. These finding were comparable to results obtained with human plasma. PMID:18582588

  19. Density distribution of currents induced inside the brain in the head part of the human model exposed to power frequency electric field

    Energy Technology Data Exchange (ETDEWEB)

    Chiba, Atsuo [Yongo National Collage of Technology (Japan); Isaka, Katsuo [University of Tokushima (Japan)

    1999-07-01

    The health effect of the weak current induced in the human body as a result of the interaction between human body and power frequency electric fields has been investigated. However, the current density inside the head part tissues of the human body exposed to the electric fields has rarely been discussed. In this paper, the finite element method is applied to the analysis of the current density distribution of the head part composed of scalp, skull, cerebrospinal liquid and brain tissues. The basic characteristics of the current density distributions of the brain in the asymmetrical human model have been made clear. (author)

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

    Science.gov (United States)

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

    2017-03-21

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

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

    Directory of Open Access Journals (Sweden)

    Hai Long Li

    2014-03-01

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

  2. Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

    Directory of Open Access Journals (Sweden)

    Sadlier Denise M

    2007-02-01

    Full Text Available Abstract Background Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. Methods In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. Results These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. Conclusion The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis.

  3. Antioxidant Activity of Ixora parviflora in a Cell/Cell-Free System and in UV-Exposed Human Fibroblasts

    Directory of Open Access Journals (Sweden)

    Hsiu-Mei Chiang

    2011-07-01

    Full Text Available Polyphenols and flavonoids possess a variety of biological activities including antioxidant and anti-tumor activities. Ixora parviflora is a member of the flavonoid-rich Rubiaceae family of flowering plants and used as folk medicine in India. The aim of this study was to investigate the antioxidant activity of Ixora parviflora extract (IPE in a cell-free system and erythrocytes, and the ability of IPE to inhibit reactive oxygen species (ROS generation in human fibroblasts (Hs68 after ultraviolet (UV exposure. Various in vitro antioxidant assays were employed in this study. The extraction yield of IPE was 17.4 ± 3.9%, the total phenolic content of IPE was 26.2 μg gallic acid equivalent (GAE/mg leaves dry weight and the total flavonoids content was 54.2 ± 4.4 μg quercetin equvalent (QE/mg extract. The content of chlorogenic acid was 9.7 ± 1.2 mg/g extract. IPE at 1000 μg/mL exhibited a reducing capacity of 90.5 ± 0.6%, a 1,1-diphenyl-2-picrylhydrazy (DPPH radical scavenging activity of 96.0 ± 0.4%, a ferrous chelating activity of 72.2 ± 3.5%, a hydroxyl radical scavenging activity of 96.8 ± 1.4%, and a hydrogen peroxide scavenging activity of 99.5 ± 3.3%. IPE at 500 μg/mL also possessed inhibitory activity against 2,2'-azobis (2-methylpropionamidine dihydrochloride (AAPH-induced hemolysis of erythrocytes (89.4 ± 1.8% and resulted in a 52.9% reduction in ROS generation in UV-exposed fibroblasts. According to our findings, IPE is a potent antioxidant and a potential anti-photoaging agent.

  4. Incidence of micronuclei in human peripheral blood lymphocytes exposed to modulated and unmodulated 2450 MHz radiofrequency fields.

    Science.gov (United States)

    Vijayalaxmi; Reddy, Abhishek B; McKenzie, Raymond J; McIntosh, Robert L; Prihoda, Thomas J; Wood, Andrew W

    2013-10-01

    Peripheral blood samples from four healthy volunteers were collected and aliquots were exposed in vitro for 2 h to either (i) modulated (wideband code division multiple access, WCDMA) or unmodulated continuous wave (CW) 2450 MHz radiofrequency (RF) fields at an average specific absorption rate of 10.9 W/kg or (ii) sham-exposed. Aliquots of the same samples that were exposed in vitro to an acute dose of 1.5 Gy ionizing gamma-radiation (GR) were used as positive controls. Half of the aliquots were treated with melatonin (Mel) to investigate if such treatment offers protection to the cells from the genetic damage, if any, induced by RF and GR. The cells in all samples were cultured for 72 h and the lymphocytes were examined to determine the extent of genetic damage assessed from the incidence of micronuclei (MN). The results indicated the following: (i) the incidence of MN was similar in incubator controls, and those exposed to RF/sham and Mel alone; (ii) there were no significant differences between WCDMA and CW RF exposures; (iii) positive control cells exposed to GR alone exhibited significantly increased MN; and (iv) Mel treatment had no effect on cells exposed to RF and sham, while such treatment significantly reduced the frequency of MN in GR-exposed cells. Copyright © 2013 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2014-01-01

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

  6. Analysis of dicentrics in human lymphocytes exposed to ionizing radiation using the automated system and optical microscope

    International Nuclear Information System (INIS)

    Martinez A, J.

    2016-01-01

    Ionizing radiation is a form of energy that produces ionizations in the molecules it traverses. When the higher energy radiation interacts with the structure of human chromosomes, chromosome aberrations, mainly of the dicentric type, are the union of two damaged chromosomes, represented by two centromeres and non centromere fragment. There are situations where a population of people may be affected by the release of any radioactive material and it is impossible to determine in a short time the absorbed dose to which each person was exposed. The dicentrics analysis from the culture of human lymphocytes is used to estimate doses of exposure to ionizing radiation, using the optical microscope. The objective of this work is to analyze dicentric chromosomal lesions, using the optical microscope in comparison with the semi-automated system, to respond promptly to radiological emergencies. For this study, two samples irradiated with "6"0Co were analyzed, one in the Instituto Nacional de Investigaciones Nucleares (ININ) reaching doses of 2.7 ± 0.1 and 0.85 ± 0.1 Gy, and the other in Walischmiller Engineering G mb H, Markdorf (Germany) reaching doses of 0.84 ± 0.3 and 2.8 ± 0.1 Gy. A lymphocyte culture was performed following the recommendations of the IAEA, using minimum essential MEM medium previously prepared with BrdU, sodium heparin, antibiotic and L-glutamine. Phytohemagglutinin, fetal calf serum was added to the sample, incubated at 37 degrees Celsius for 48 hours and three hours before the end of incubation, colcemide was placed. KCl post-culture was added and lamellae were prepared by washing with the 3:1 acid-acetic fixative solution and a Giemsa staining. 1000 cell readings were performed using the optical microscope and the automated system according to study protocols and quality standards to estimate absorbed dose by means of dicentric analysis, defined by ISO-19238. With the automated system similar results of absorbed dose were obtained with respect to

  7. Cytogenetic studies in human blood lymphocytes exposed in vitro to radiofrequency radiation at a cellular telephone frequency (835.62 MHz, FDMA).

    Science.gov (United States)

    Vijayalaxmi; Leal, B Z; Meltz, M L; Pickard, W F; Bisht, K S; Roti Roti JL; Straube, W L; Moros, E G

    2001-01-01

    Freshly collected peripheral blood samples from four healthy human volunteers were diluted with RPMI 1640 tissue culture medium and exposed in sterile T-75 tissue culture flasks in vitro for 24 h to 835.62 MHz radiofrequency (RF) radiation, a frequency employed for customer-to-base station transmission of cellular telephone communications. An analog signal was used, and the access technology was frequency division multiple access (FDMA, continuous wave). A nominal net forward power of 68 W was used, and the nominal power density at the center of the exposure flask was 860 W/m(2). The mean specific absorption rate in the exposure flask was 4.4 or 5.0 W/kg. Aliquots of diluted blood that were sham-exposed or exposed in vitro to an acute dose of 1.50 Gy of gamma radiation were used as negative or positive controls. Immediately after the exposures, the lymphocytes were stimulated with a mitogen, phytohemagglutinin, and cultured for 48 or 72 h to determine the extent of genetic damage, as assessed from the frequencies of chromosomal aberrations and micronuclei. The extent of alteration in the kinetics of cell proliferation was determined from the mitotic indices in 48-h cultures and from the incidence of binucleate cells in 72-h cultures. The data indicated no significant differences between RF-radiation- and sham-exposed lymphocytes with respect to mitotic indices, incidence of exchange aberrations, excess fragments, binucleate cells, and micronuclei. In contrast, the response of the lymphocytes exposed to gamma radiation was significantly different from both RF-radiation- and sham-exposed cells for all of these indices. Thus, under the experimental conditions tested, there is no evidence for the induction of chromosomal aberrations and micronuclei in human blood lymphocytes exposed in vitro for 24 h to 835.62 MHz RF radiation at SARs of 4.4 or 5.0 W/kg.

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

    Science.gov (United States)

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

    2012-12-15

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

  9. Risky business: rhesus monkeys exhibit persistent preferences for risky options.

    Science.gov (United States)

    Xu, Eric R; Kralik, Jerald D

    2014-01-01

    Rhesus monkeys have been shown to prefer risky over safe options in experiential decision-making tasks. These findings might be due, however, to specific contextual factors, such as small amounts of fluid reward and minimal costs for risk-taking. To better understand the factors affecting decision-making under risk in rhesus monkeys, we tested multiple factors designed to increase the stakes including larger reward amounts, distinct food items rather than fluid reward, a smaller number of trials per session, and risky options with greater variation that also included non-rewarded outcomes. We found a consistent preference for risky options, except when the expected value of the safe option was greater than the risky option. Thus, with equivalent mean utilities between the safe and risky options, rhesus monkeys appear to have a robust preference for the risky options in a broad range of circumstances, akin to the preferences found in human children and some adults in similar tasks. One account for this result is that monkeys make their choices based on the salience of the largest payoff, without integrating likelihood and value across trials. A related idea is that they fail to override an impulsive tendency to select the option with the potential to obtain the highest possible outcome. Our results rule out strict versions of both accounts and contribute to an understanding of the diversity of risky decision-making among primates.

  10. Monkey-derived monoclonal antibodies against Plasmodium falciparum

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  11. Establishment of reference values for complete blood count and blood gases in cynomolgus monkeys (Macaca fascicularis)

    Science.gov (United States)

    NAKAYAMA, Shunya; KOIE, Hiroshi; KANAYAMA, Kiichi; KATAKAI, Yuko; ITO-FUJISHIRO, Yasuyo; SANKAI, Tadashi; YASUTOMI, Yasuhiro; AGEYAMA, Naohide

    2017-01-01

    Cynomolgus monkeys are closely related to humans phylogenetically, and this has resulted in their widespread use as a preclinical model. Hematological data with regard to these monkeys are thus important. Although reference values for blood components and sex hormones have been established for cynomolgus monkeys, those for arterial blood gases have not. The arterial blood gases quickly reflect respiratory and circulatory dynamics, and are thus useful for animal management and safe general anesthesia and surgical operations. Furthermore, since O2 is transported by RBC, CBC and blood gases are closely related. The present study aimed to establish reference values for arterial blood gases and CBC in cynomolgus monkeys over a wide age range. Blood gases and CBC of arterial blood, collected from 41 female and 21 male anesthetized monkeys, were measured. Age correlated with RBC, HGB and HCT in the CBC. Values differed significantly between males and females in pCO2, CO2 concentration, MCV and MCH. The pH of blood was equivalent to that of humans and pCO2 was more stable, whereas MCV and MCH were lower than those in humans. Erythrocytes were smaller and less pigmented than in other Macaca species. Several relationships between gender and age, and blood gases and CBC were identified in cynomolgus monkeys. In conclusion, these reference values will be useful as markers for veterinary applications and in the care and maintenance of these animals. PMID:28381665

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

    Science.gov (United States)

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

    2014-01-01

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

  13. The Effect of Extremely Low Frequency Electromagnetic Fields on Visual Learning & Memory and Anatomical Structures of the Brain in Male Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    Elahe Tekieh

    2018-04-01

    Full Text Available Background: Humans in modern societies expose to substantially elevated levels of electromagnetic field (EMF emissions with different frequencies.The neurobiological effects of EMF have been the subject of debate and intensive research over the past few decades. Therefore, we evaluated the effects of EMF on visual learning and anatomical dimensions of the hippocampus and the prefrontal area (PFA in male Rhesus monkeys. Materials and Methods:In this study, four rhesus monkeys were irradiated by 0.7 microtesla ELF-EMF either at 5 or 30 Hz, 4 h a day, for 30 days. Alterations in visual learning and memory were assessed before and after irradiation phase by using a box designed that cchallenging animals for gaining rewards Also, the monkeys’ brains were scanned by using MRI technique one week before and one week after irradiation. The monkeys were anesthetized by intramuscular injection of ketamine hydrochloride (10–20 mg/kg and xylazine (0.2–0.4 mg/kg, and scanned with a 3-Tesla Magnetom, in axial, sagittal, and coronal planes using T2 weight­ed protocol with a slice thickness of 3 mm. The anatomical changes of hippocampus and the prefrontal area (PFA was measured by volumetric study. Results: Electromagnetic field exposure at a frequency of 30 Hz reduced the number of correct responses in the learning process and delayed memory formation in the two tested monkeys. While, ELF-EMF at 5 Hz had no effect on the visual learning and memory changes. No anatomical changes were found in the prefrontal area and the hippocampus at both frequencies. Conclusion: ELF-EMF irradiation at 30 Hz adversely affected visual learning and memory, pprobably through these changes apply through effects on other factors except changes in brain structure and anatomy.

  14. Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

    International Nuclear Information System (INIS)

    Vasin, Mikhail V.; Antipov, Vsevolod V.; Ushakov, Igor B.; Semenov, Leonid F.; Lapin, Boris A.; Suvorov, Nikolai N.; Ilyin, Leonid A.

    2014-01-01

    The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2-3-years-old and weighing 2.1-3.5 kg were used. Animals were exposed to total-body gamma irradiation from 60 Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40-120 mg kg -1 ) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg -1 protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3-94.3) mg kg -1 , and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg -1 . Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys. (author)

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  16. DNA damage response and role of shelterin complex in human peripheral blood mononuclear cells exposed to gamma radiation

    International Nuclear Information System (INIS)

    Saini, Divyalakshmi; Das, Birajalaxmi

    2013-01-01

    Telomeres are the DNA protein structures that cap the ends of linear DNA. It consists of short repetitive DNA sequences (TTAGGG)n and specialized telomere binding proteins. There are six telomeric proteins (TRF1, TRF2, TIN2, TERF2, PTOP and POT1) called as shelterin complex/telosome which maintains telomere integrity. The function of this 'telosome' is to protect the natural ends of the chromosomes from being recognized as artificial DNA breaks, thereby preventing chromosome end-to-end fusions. DNA Damage Response (DDR) induced by radiation and its interaction with telomeric protein complex is poorly understood in human PBMCs at G 0 stage. Alterations in either telomeric DNA or telomere binding proteins can impair the function of the telosome, which may lead to senescence or apoptosis. Ionizing radiation which induces a plethora of DNA lesions in human cell may also alter the expression of telomere associated proteins. In the present study, we have made an attempt to study the DNA damage response of telomere proteins in human peripheral blood mononuclear cells exposed to gamma radiation. Venous blood samples were collected from eight random healthy volunteers and PBMCs were separated. Dose response as well as time point kinetics study was carried out at transcription as well as protein level. PBMCs were irradiated at various doses between 10 cGy to 2.0 Gy at a dose rate of 1.0 Gy/min. Total RNA was isolated for gene expression analysis at 0 hour and 4 hours respectively. cDNA was prepared and transcriptional pattern as studied using real time q-PCR where Taqman probes were used. Time point kinetics of transcriptional pattern of TRF1, TRF2, TIN2, TERF2, PTOP and POT1 was carried out at 0 min, 15 min, 30 min, 60 min, and 120 min for two different doses (1.0 Gy and 2.0 Gy). Dose response and time point kinetics of TRF2 was studied at similar doses using confocal microscopy. Our results revealed that at 2.0 Gy there was a two fold increase at the level of transcription

  17. Health risk assessment on human exposed to heavy metals in the ambient air PM10 in Ahvaz, southwest Iran

    Science.gov (United States)

    Goudarzi, Gholamreza; Alavi, Nadali; Geravandi, Sahar; Idani, Esmaeil; Behrooz, Hamid Reza Adeli; Babaei, Ali Akbar; Alamdari, Farzaneh Aslanpour; Dobaradaran, Sina; Farhadi, Majid; Mohammadi, Mohammad Javad

    2018-02-01

    Heavy metals (HM) are one of the main components of urban air pollution. Today, megacities and industrial regions in southwest of Iran are frequently suffering from severe haze episodes, which essentially caused by PM10-bound heavy metals. The purpose of this study was to evaluate the health risk assessment on human exposed to heavy metals (Cr, Ni, Pb, and Zn) in the ambient air PM10 in Ahvaz, southwest Iran. In this study, we estimated healthy people from the following scenarios: (S3) residential site; (S2) high-traffic site; (S1) industrial site in Ahvaz metropolitan during autumn and winter. In the current study, high-volume air samplers equipped with quartz fiber filters were used to sampling and measurements of heavy metal concentration. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was utilized for detection of heavy metal concentration (ng m-3). Also, an estimate of the amount of health risk assessment (hazard index) of Cr, Ni, Pb, and Zn of heavy metal exposure to participants was used. Result of this study showed that the residential and industrial areas had the lowest and the highest level of heavy metal. Based on the result of this study, average levels of heavy metal in industrial, high-traffic, and residential areas in autumn and winter were 31.48, 30.89, and 23.21 μg m-3 and 42.60, 37.70, and 40.07 μg m-3, respectively. Based on the result of this study, the highest and the lowest concentration of heavy metal had in the industrial and residential areas. Zn and Pb were the most abundant elements among the studied PM10-bound heavy metals, followed by Cr and Ni. The carcinogenic risks of Cr, Pb, and the integral HQ of metals in PM10 for children and adults via inhalation and dermal exposures exceeded 1 × 10-4 in three areas. Also, based on the result of this study, the values of hazard index (HI) of HM exposure in different areas were significantly higher than standard. The health risks attributed to HM should be further

  18. Health risk assessment on human exposed to heavy metals in the ambient air PM10 in Ahvaz, southwest Iran.

    Science.gov (United States)

    Goudarzi, Gholamreza; Alavi, Nadali; Geravandi, Sahar; Idani, Esmaeil; Behrooz, Hamid Reza Adeli; Babaei, Ali Akbar; Alamdari, Farzaneh Aslanpour; Dobaradaran, Sina; Farhadi, Majid; Mohammadi, Mohammad Javad

    2018-06-01

    Heavy metals (HM) are one of the main components of urban air pollution. Today, megacities and industrial regions in southwest of Iran are frequently suffering from severe haze episodes, which essentially caused by PM 10 -bound heavy metals. The purpose of this study was to evaluate the health risk assessment on human exposed to heavy metals (Cr, Ni, Pb, and Zn) in the ambient air PM 10 in Ahvaz, southwest Iran. In this study, we estimated healthy people from the following scenarios: (S3) residential site; (S2) high-traffic site; (S1) industrial site in Ahvaz metropolitan during autumn and winter. In the current study, high-volume air samplers equipped with quartz fiber filters were used to sampling and measurements of heavy metal concentration. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was utilized for detection of heavy metal concentration (ng m -3 ). Also, an estimate of the amount of health risk assessment (hazard index) of Cr, Ni, Pb, and Zn of heavy metal exposure to participants was used. Result of this study showed that the residential and industrial areas had the lowest and the highest level of heavy metal. Based on the result of this study, average levels of heavy metal in industrial, high-traffic, and residential areas in autumn and winter were 31.48, 30.89, and 23.21 μg m -3 and 42.60, 37.70, and 40.07 μg m -3 , respectively. Based on the result of this study, the highest and the lowest concentration of heavy metal had in the industrial and residential areas. Zn and Pb were the most abundant elements among the studied PM 10 -bound heavy metals, followed by Cr and Ni. The carcinogenic risks of Cr, Pb, and the integral HQ of metals in PM 10 for children and adults via inhalation and dermal exposures exceeded 1 × 10 -4 in three areas. Also, based on the result of this study, the values of hazard index (HI) of HM exposure in different areas were significantly higher than standard. The health risks attributed to HM should

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

    Science.gov (United States)

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

    2015-04-18

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

  20. Tonal frequency affects amplitude but not topography of rhesus monkey cranial EEG components.

    Science.gov (United States)

    Teichert, Tobias

    2016-06-01

    The rhesus monkey is an important model of human auditory function in general and auditory deficits in neuro-psychiatric diseases such as schizophrenia in particular. Several rhesus monkey studies have described homologs of clinically relevant auditory evoked potentials such as pitch-based mismatch negativity, a fronto-central negativity that can be observed when a series of regularly repeating sounds is disrupted by a sound of different tonal frequency. As a result it is well known how differences of tonal frequency are represented in rhesus monkey EEG. However, to date there is no study that systematically quantified how absolute tonal frequency itself is represented. In particular, it is not known if frequency affects rhesus monkey EEG component amplitude and topography in the same way as previously shown for humans. A better understanding of the effect of frequency may strengthen inter-species homology and will provide a more solid foundation on which to build the interpretation of frequency MMN in the rhesus monkey. Using arrays of up to 32 cranial EEG electrodes in 4 rhesus macaques we identified 8 distinct auditory evoked components including the N85, a fronto-central negativity that is the presumed homolog of the human N1. In line with human data, the amplitudes of most components including the N85 peaked around 1000 Hz and were strongly attenuated above ∼1750 Hz. Component topography, however, remained largely unaffected by frequency. This latter finding may be consistent with the known absence of certain anatomical structures in the rhesus monkey that are believed to cause the changes in topography in the human by inducing a rotation of generator orientation as a function of tonal frequency. Overall, the findings are consistent with the assumption of a homolog representation of tonal frequency in human and rhesus monkey EEG. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Monitoring the genetic health of humans accidentally exposed to ionizing radiation of Cesium-137 in Goiania (Brazil)

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, A. da; Glickman, B.W. [Victoria Univ., BC (Canada). Dept. of Biology. Centre for Environmental Health

    1997-12-31

    A long-term genetic monitoring of the Goiania population exposed to ionizing radiation of Cesium-137 is described using cytogenetic and molecular endpoints. Two molecular methods were employed: the hprt clonal assay, involving in vitro selection of 6-thioguanine-resistant hprt mutant clones which were characterized at the molecular level using RT-PCR and genomic analysis. Ionizing radiation exposure initially elevated hprt mutation frequency which gradually diminished, so that no significant increase was observed 4.5 years after original exposure. The spectrum of hprt mutation recovered from 10 individuals exposed to relatively high doses of radiation revealed a 4-fold increase in the frequency of A:T{yields}G:C transitions. Additionally, a two-fold increase in the frequency of deletions was observed which may reflect radiation-induced DNA strand breakage; determination of micro satellite instability using fluorescent PCR and genomic DNA from mononuclear cells. The frequency distribution of somatic micro satellite alterations in exposed and non-exposed populations were not different. We estimated the risk associated with radiation exposure for the exposed Goiania population. The estimated genetic risk of dominant disorders in the first post-exposure generation was increased by approximately a 24-fold. The risk of carcinogenesis was increased by a factor of 1.5 13 refs.; e-mail: acruz at uvic.ca.; bwglick at uvic.ca

  2. Role of VEGF-A in endothelial phenotypic shift in human diabetic retinopathy and VEGF-A-induced retinopathy in monkeys

    NARCIS (Netherlands)

    Hofman, P.; Blaauwgeers, H. G.; Vrensen, G. F.; Schlingemann, R. O.

    2001-01-01

    The endothelium-specific antigen PAL-E, associated with transport vesicles in non-barrier endothelium, is almost absent from barrier capillaries in the normal brain and retina. We have recently demonstrated that only leaking retinal capillaries in diabetic retinopathy (DR) in humans

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

  6. Emesis in monkeys following exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Middleton, G.R.; Young, R.W.

    1975-01-01

    There were 129 male rhesus monkeys (Macaca mulatta) exposed to prompt radiations (neutron/gamma = 0.4 and pulse width = 50 ms) ranging from 700 to 5600 rad (midhead dose). The animals were fasted 18 h preexposure and observed for incidence of vomiting for 2 h postexposure. For doses less than 1000 rads, the number of animals that vomited increased directly with dose. Above 1000 rads, the number of animals that vomited decreased with increasing dose. The total number of vomits per dose group followed a nearly identical pattern to the incidence of emesis. In all dose groups, most of the emetic episodes occurred between 20 and 50 min postirradiation

  7. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to 60Co at single fraction

    Directory of Open Access Journals (Sweden)

    Lídia Maria Andrade

    2005-10-01

    Full Text Available Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC exposed in vitro to 60 Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min-1 rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by 60Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nuclus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.Radioterapia utilizando radiação gama é uma modalidade comum no tratamento do câncer de mama. A proposta deste estudo é investigar a resposta biológica in vitro da linhagem celular MDAMB-231 de câncer de mama humano e células do sangue periférico humano (PBMC expostas à irradiação pelo Co60 em frações simples de 10Gy, 25Gy e 50Gy e 136,4cGy min-1 rate. As células foram irradiadas a temperatura ambiente usando o equipamento de radioterapia Theratron 80 radiotherapy system. A resposta biológica, após irradiação gama, foi avaliada através do ensaio do MTT para viabilidade celular e o do ensaio com Iodeto de Propídio para visualização do dano nuclear, além da eletroforese em gel de agarose. Os danos nucleares induzidos pelo Co60 foram comparados aos danos causados pela exposição das células à solução de metanol a 10%. Nós observamos que a dose de 50Gy não estimulou a mesma quantidade de danos nucleares que a solução de metanol a 10% nas c

  8. Analogical reasoning and the differential outcome effect: transitory bridging of the conceptual gap for rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Flemming, Timothy M; Thompson, Roger K R; Beran, Michael J; Washburn, David A

    2011-07-01

    Monkeys, unlike chimpanzees and humans, have a marked difficulty acquiring relational matching-to-sample (RMTS) tasks that likely reflect the cognitive foundation upon which analogical reasoning rests. In the present study, rhesus monkeys (Macaca mulatta) completed a categorical (identity and nonidentity) RMTS task with differential reward (pellet ratio) and/or punishment (timeout ratio) outcomes for correct and incorrect choices. Monkeys in either differential reward-only or punishment-only conditions performed at chance levels. However, the RMTS performance of monkeys experiencing both differential reward and punishment conditions was significantly better than chance. Subsequently when all animals experienced nondifferential outcomes tests, their RMTS performance levels were at chance. These results indicate that combining differential reward and punishment contingencies provide an effective, albeit transitory, scaffolding for monkeys to judge analogical relations-between-relations. PsycINFO Database Record (c) 2011 APA, all rights reserved

  9. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects tooth development in rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Iku; Kazuhiro, Tsuga; Yasumasa, Akagawa [Hiroshima Univ. (Japan); Mineo, Yasuda; Hiroshi, Sumida [Hiroshima International Univ. (Japan); Akihiro, Arima; Toshio, Ihara [Shin Nippon Biomedical Laboratories, Ltd., Kagoshima (Japan); Shunichiro, Kubota [Tokyo Univ. (Japan); Kazuo, Asaoka [Kyoto Univ., Inuyama (Japan). Primate Research Institute; Takumi, Takasuga [Shimadzu Techno-Research Inc., Kyoto (Japan)

    2004-09-15

    The current tolerable daily intake (TDI) of dioxin and dioxin related compounds has been set at 4 pg TEQ/kg/day in Japan. This value was calculated from the lowest-observed-adverse-effect level (LOAEL) in experimental animals, mostly rodents. Gray et al. reported that a single oral dose of 200 ng/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pregnant rats on day 15 of gestation resulted in abnormalities of reproductive organs in the offspring. The maternal body burden at this dose was measured to be 86 ng/kg. To attain this body burden level, human daily intake was calculated to be 43.6 pg/kg/day. An uncertainty factor of 10 was applied to this value, and the human TDI was established. However, due to great differences in the biological half life of TCDD between human and rodents, the validity of this calculation is questioned. To obtain more reliable LOAEL in the second generation, we initiated a long-term study in rhesus monkeys in 1999. In rodents, teeth are known to be targets of developmental toxicity of dioxin. In utero and lactational TCDD exposure affects rat incisor and molar development. In humans also tooth abnormalities were reported among populations exposed to dioxins. In our monkey experiment, some young were stillborn or died neonatally. These animals provided us with a unique opportunity to study tooth development in primate young exposed to TCDD in utero and lactationally. By macroscopic observation we found some tooth abnormalities among died young exposed to TCDD5. This prompted us to examine surviving young by radiography. This is an interim report of our findings in these young.

  10. Comparative Immunogenicity in Rhesus Monkeys of DNA Plasmid, Recombinant Vaccinia Virus, and Replication-Defective Adenovirus Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene

    OpenAIRE

    Casimiro, Danilo R.; Chen, Ling; Fu, Tong-Ming; Evans, Robert K.; Caulfield, Michael J.; Davies, Mary-Ellen; Tang, Aimin; Chen, Minchun; Huang, Lingyi; Harris, Virginia; Freed, Daniel C.; Wilson, Keith A.; Dubey, Sheri; Zhu, De-Min; Nawrocki, Denise

    2003-01-01

    Cellular immune responses, particularly those associated with CD3+ CD8+ cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1). Accordingly, recent HIV-1 vaccine research efforts have focused on establishing the optimal means of eliciting such antiviral CTL immune responses. We evaluated several DNA vaccine formulations, a modified vaccinia virus Ankara vector, and a replication-defecti...

  11. Monkey Management: Using Spatial Ecology to Understand the Extent and Severity of Human-Baboon Conflict in the Cape Peninsula, South Africa

    Directory of Open Access Journals (Sweden)

    Tali S. Hoffman

    2012-09-01

    Full Text Available Conflict with humans poses one of the greatest threats to the persistence and survival of all wildlife. In the Cape Peninsula, South Africa, human-baboon conflict levels remain high despite substantial investment by conservation authorities in a variety of mitigation measures. Here we explore how spatial ecology can inform wildlife managers on the extent and severity of both current and projected human-baboon conflict. We apply conservative and generous densities - 2.3 and 5.9 baboons/km2 - to hypothetical landscape management scenarios to estimate whether the chacma baboon (Papio ursinus population in the Cape Peninsula is currently overabundant. We correlate conflict indices with spatial variables to explain intertroop differences in conflict levels. We investigate how an understanding of key elements of baboon ecology, including sleeping-site characteristics and intertroop territoriality, can direct management efforts and mitigate conflict. Our findings suggest that the current population of 475 baboons is below even the most conservative density estimate and that the area could potentially sustain up to 799 baboons. Conflict levels correlated positively with the loss of access to low-lying land through habitat transformation (Pearson r = 0.77, p = 0.015, n = 9 troops, and negatively with the distance of sleeping sites from the urban edge (Pearson r = 0.81, p = 0.001, n = 9 troops. Despite the availability of suitable sleeping sites elsewhere, more than half of all troops slept

  12. Full-length cDNA sequences from Rhesus monkey placenta tissue: analysis and utility for comparative mapping

    Directory of Open Access Journals (Sweden)

    Lee Sang-Rae

    2010-07-01

    Full Text Available Abstract Background Rhesus monkeys (Macaca mulatta are widely-used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as cynomolgus monkeys (Macaca fascicularis, and to humans, sharing a last common ancestor from about 25 million years ago. Although rhesus monkeys have been studied extensively under field and laboratory conditions, research has been limited by the lack of genetic resources. The present study generated placenta full-length cDNA libraries, characterized the resulting expressed sequence tags, and described their utility for comparative mapping with human RefSeq mRNA transcripts. Results From rhesus monkey placenta full-length cDNA libraries, 2000 full-length cDNA sequences were determined and 1835 rhesus placenta cDNA sequences longer than 100 bp were collected. These sequences were annotated based on homology to human genes. Homology search against human RefSeq mRNAs revealed that our collection included the sequences of 1462 putative rhesus monkey genes. Moreover, we identified 207 genes containing exon alterations in the coding region and the untranslated region of rhesus monkey transcripts, despite the highly conserved structure of the coding regions. Approximately 10% (187 of all full-length cDNA sequences did not represent any public human RefSeq mRNAs. Intriguingly, two rhesus monkey specific exons derived from the transposable elements of AluYRa2 (SINE family and MER11B (LTR family were also identified. Conclusion The 1835 rhesus monkey placenta full-length cDNA sequences described here could expand genomic resources and information of rhesus monkeys. This increased genomic information will greatly contribute to the development of evolutionary biology and biomedical research.

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

    Directory of Open Access Journals (Sweden)

    N. Chowdhury

    2014-01-01

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

  14. High hepatitis E virus antibody positive rates in dogs and humans exposed to dogs in the south-west of China.

    Science.gov (United States)

    Zeng, M Y; Gao, H; Yan, X X; Qu, W J; Sun, Y K; Fu, G W; Yan, Y L

    2017-12-01

    Hepatitis E (HE) is a zoonotic viral disease caused by hepatitis E virus (HEV). The objective of this study was to investigate the prevalence of HEV infection among dogs and humans exposed to dogs in the south-west region of China. A total of 4,490 dog serum samples and 2,206 relative practitioner serum samples were collected from 18 pet hospitals and dog farms in Yunnan, Sichuan and Guizhou province, and the anti-HEV IgG antibodies were detected by ELISA. The results showed that the total positive rate of anti-HEV antibodies was 36.55% with the highest rate in city stray dogs, and the differences in distinct species and growth phases were significant. The positive rate of anti-HEV antibody in veterinarian and farm staff-related practitioners was significantly higher than the general population. The finding of the present survey suggested that high HEV seroprevalence in dogs and humans exposed to dogs in the south-west area of China poses a significant public health concern. It is urgent to improve integrated strategies to detect, prevent and control HEV infection in dogs and humans exposed to dogs in this area. © 2017 Blackwell Verlag GmbH.

  15. Genetic damage in human cells exposed to non-ionizing radiofrequency fields: a meta-analysis of the data from 88 publications (1990-2011).

    Science.gov (United States)

    Vijayalaxmi; Prihoda, Thomas J

    2012-12-12

    Based on the 'limited' evidence suggesting an association between exposure to radiofrequency fields (RF) emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as 'possibly carcinogenic to humans' in group 2B. In view of this classification and the positive correlation between increased genetic damage and carcinogenesis, a meta-analysis was conducted to determine whether a significant increase in genetic damage in human cells exposed to RF provides a potential mechanism for its carcinogenic potential. The extent of genetic damage in human cells, assessed from various end-points, viz., single-/double-strand breaks in the DNA, incidence of chromosomal aberrations, micronuclei and sister chromatid exchanges, reported in a total of 88 peer-reviewed scientific publications during 1990-2011 was considered in the meta-analysis. Among the several variables in the experimental protocols used, the influence of five specific variables related to RF exposure characteristics was investigated: (i) frequency, (ii) specific absorption rate, (iii) exposure as continuous wave, pulsed wave and occupationally exposed/mobile phone users, (iv) duration of exposure, and (v) different cell types. The data indicated the following. (1) The magnitude of difference between RF-exposed and sham-/un-exposed controls was small with some exceptions. (2) In certain RF exposure conditions there was a statistically significant increase in genotoxicity assessed from some end-points: the effect was observed in studies with small sample size and was largely influenced by publication bias. Studies conducted within the generally recommended RF exposure guidelines showed a smaller effect. (3) The multiple regression analyses and heterogeneity goodness of fit data indicated that factors other than the above five variables as well as the quality of publications have contributed to the overall results. (4) More

  16. Cup tool use by squirrel monkeys.

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

  18. Rhesus monkeys attribute perceptions to others.

    Science.gov (United States)

    Flombaum, Jonathan I; Santos, Laurie R

    2005-03-08

    Paramount among human cognitive abilities is the capacity to reason about what others think, want, and see--a capacity referred to as a theory of mind (ToM). Despite its importance in human cognition, the extent to which other primates share human ToM capacities has for decades remained a mystery. To date, primates [1, 2] have performed poorly in behavioral tasks that require ToM abilities, despite the fact that some macaques are known to encode social stimuli at the level of single neurons [3-5]. Here, we presented rhesus macaques with a more ecologically relevant ToM task in which subjects could "steal" a contested grape from one of two human competitors. In six experiments, monkeys selectively retrieved the grape from an experimenter who was incapable of seeing the grape rather than an experimenter who was visually aware. These results suggest that rhesus macaques possess an essential component of ToM: the ability to deduce what others perceive on the basis of where they are looking. These results converge with new findings illustrating the importance of competitive paradigms in apes [6]. Moreover, they raise the possibility that, in primates, cortical cells thought to encode where others are looking [7] may encode what those individuals see as well.

  19. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11.

    Science.gov (United States)

    Lundegaard, Claus; Lamberth, Kasper; Harndahl, Mikkel; Buus, Søren; Lund, Ole; Nielsen, Morten

    2008-07-01

    NetMHC-3.0 is trained on a large number of quantitative peptide data using both affinity data from the Immune Epitope Database and Analysis Resource (IEDB) and elution data from SYFPEITHI. The method generates high-accuracy predictions of major histocompatibility complex (MHC): peptide binding. The predictions are based on artificial neural networks trained on data from 55 MHC alleles (43 Human and 12 non-human), and position-specific scoring matrices (PSSMs) for additional 67 HLA alleles. As only the MHC class I prediction server is available, predictions are possible for peptides of length 8-11 for all 122 alleles. artificial neural network predictions are given as actual IC(50) values whereas PSSM predictions are given as a log-odds likelihood scores. The output is optionally available as download for easy post-processing. The training method underlying the server is the best available, and has been used to predict possible MHC-binding peptides in a series of pathogen viral proteomes including SARS, Influenza and HIV, resulting in an average of 75-80% confirmed MHC binders. Here, the performance is further validated and benchmarked using a large set of newly published affinity data, non-redundant to the training set. The server is free of use and available at: http://www.cbs.dtu.dk/services/NetMHC.

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory

    2009-01-01

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

  2. The AL 333-160 fourth metatarsal from Hadar compared to that of humans, great apes, baboons and proboscis monkeys: non-conclusive evidence for pedal arches or obligate bipedality in Hadar hominins.

    Science.gov (United States)

    Mitchell, P J; Sarmiento, E E; Meldrum, D J

    2012-10-01

    Based on comparisons to non-statistically representative samples of humans and two great ape species (i.e. common chimpanzees Pan troglodytes and lowland gorillas Gorilla gorilla), Ward et al. (2011) concluded that a complete hominin fourth metatarsal (4th MT) from Hadar, AL 333-160, belonged to a committed terrestrial biped with fixed transverse and longitudinal pedal arches, which was no longer under selection favoring substantial arboreal behaviors. According to Ward et al., the Hadar 4th MT had (1) a torsion value indicating a transverse arch, (2) sagittal plane angles between the diaphyseal long axis and the planes of the articular surfaces indicating a longitudinal arch, and (3) a narrow mediolateral to dorsoplantar base ratio, an ectocuneiform facet, and tarsal articular surface contours all indicating a rigid foot without an ape-like mid-tarsal break. Comparisons of the Hadar 4th MT characters to those of statistically representative samples of humans, all five great ape species, baboons and proboscis monkeys show that none of the correlations Ward et al. make to localized foot function were supported by this analysis. The Hadar 4th MT characters are common to catarrhines that have a midtarsal break and lack fixed transverse or longitudinal arches. Further comparison of the AL 333-160 4th MT length, and base, midshaft and head circumferences to those of catarrhines with field collected body weights show that this bone is uniquely short with a large base. Its length suggests the AL 333-160 individual was a poor leaper with limited arboreal behaviors and lacked a longitudinal arch, i.e. its 4th MT long axis was usually held perpendicular to gravity. Its large base implies cuboid-4th MT joint mobility. A relatively short 4th MT head circumference indicates AL 333-160 had small proximal phalanges with a restricted range of mobility. Overall, AL 333-160 is most similar to the 4th MT of eastern gorillas, a slow moving quadruped that sacrifices arboreal behaviors

  3. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress

    Science.gov (United States)

    Gould, Elizabeth; Tanapat, Patima; McEwen, Bruce S.; Flügge, Gabriele; Fuchs, Eberhard

    1998-01-01

    Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and ≈80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience. PMID:9501234

  4. Monkeys Wait to Begin a Computer Task when Waiting Makes Their Responses More Effective

    Directory of Open Access Journals (Sweden)

    Theodore A. Evans

    2014-02-01

    Full Text Available Rhesus monkeys (Macaca mulatta and capuchin monkeys (Cebus apella performed a computerized inhibitory control task modeled after an “escalating interest task” from a recent human study (Young, Webb, & Jacobs, 2011. In the original study, which utilized a first-person shooter game, human participants learned to inhibit firing their simulated weapon long enough for the weapon‟s damage potential to grow in effectiveness (up to 10 seconds in duration. In the present study, monkeys earned food pellets for eliminating arrays of target objects using a digital eraser. We assessed whether monkeys could suppress trial-initiating joystick movements long enough for the eraser to grow in size and speed, thereby making their eventual responses more effective. Monkeys of both species learned to inhibit moving the eraser for as long as 10 seconds, and they allowed the eraser to grow larger for successively larger target arrays. This study demonstrates an interesting parallel in behavioral inhibition between human and nonhuman participants and provides a method for future comparative testing of human and nonhuman test groups.

  5. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    International Nuclear Information System (INIS)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo

    1996-01-01

    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

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

    Science.gov (United States)

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

    2007-12-15

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

  7. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

  8. Bioassay of circulating luteinizing hormone in the rhesus monkey: comparison with radioimmunoassay during physiological changes

    International Nuclear Information System (INIS)

    Dufau, M.L.; Hodgen, G.D.; Goodman, A.L.; Catt, K.J.

    1977-01-01

    The concentration of biologically active LH in Rhesus monkey (Macaca mulatta) serum was measured by a highly sensitive bioassay based upon testosterone production by dispersed rat interstitial cells. The sensitivity of the in vitro bioassay was equal to or higher than that of radioimmunoassay, with detection limits of 0.1 mIU of human menopausal gonadotropin (hMG) or 10 ng of a Rhesus pituitary gonadotropin preparation (LER-1909-2). Parallel dose-response curves were obtained for hMG and Rhesus monkey pituitary gonadotropin. The method permits bioassay of LH in 20--100 μl of serum from adult male monkeys, and from female monkeys during the follicular and luteal phases of the menstrual cycle. Bioactive LH concentrations could be assayed in 0.25 to 5 μl of serum from mid-cycle, postmenopausal, and castrated female monkeys. Serum LH was undetectable in two hypophysectomized adult female monkeys and six intact immature animals, and was 13 +- 6 (SD) mIU/ml in adult male monkeys. In adult females, follicular phase LH levels ranged from 17 to 169 mIU/ml, with a mean of 76 +- 52 mIU/ml. The midcycle LH peak was 1738 +- 742 mIU/ml and the luteal phase values ranged from 6-47 mIU/ml, with a mean of 35 +- 5 mIU/ml. Serum LH concentrations ranged from 100 to 900 mIU/ml in two menopausal females, and from 590--1480 mIU/ml in castrated females. Treatment of castrated female monkeys with estrogen plus progesterone produced an initial two-fold rise in sepum LH within 3 days, followed by a gradual decline to one-fourth to one-tenth of the initial levels after 10 days of treatment. Serum LH was suppressed to undetectable levels during the third week, and remained so for the duration of the 60-day treatment period

  9. The Monkey Puzzle: A Systematic Review of Studies of Stress, Social Hierarchies, and Heart Disease in Monkeys

    Science.gov (United States)

    Petticrew, Mark; Davey Smith, George

    2012-01-01

    Background It is often suggested that psychosocial factors, such as stress, or one's social position, may play an important role in producing social gradients in human disease. Evidence in favour of this model of health inequalities has relied, in part, on studies of the health effects of the natural social hierarchies found among non-human primates. This study aimed to assess the strength of this evidence. Methodology/Principal Findings A systematic review was carried out to identify all studies of psychosocial factors and coronary artery disease (CAD) in non-human primates. We searched databases (MEDLINE, PsycInfo, EMBASE, and Primatelit from inception to November 2010) to identify experimental and observational studies of the impact of social reorganisation, social instability, and disruption of dominance hierarchies on primate CAD outcomes. We also handsearched bibliographies and examined the citations to those studies in public health articles. Fourteen studies were found which presented evidence on CAD and social status and/or psychosocial stress. These suggested that the association between social status and disease may be sex-specific: in female monkeys dominant status may be protective, with subordinate females having a greater extent of atherosclerosis. In male monkeys the reverse may be the case. Conclusions/Significance Overall, non-human primate studies present only limited evidence for an association between social status and CAD, Despite this, there is selective citation of individual non-human primate studies in reviews and commentaries relating to human disease aetiology. Such generalisation of data from monkey studies to human societies does not appear warranted. PMID:22470414

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

    Science.gov (United States)

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

    2014-06-01

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

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

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

    Science.gov (United States)

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

    1999-10-25

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

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

    Science.gov (United States)

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

    2015-03-01

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

  14. Processing of pro-opiomelanocortin-derived amidated joining peptide and glycine-extended precursor in monkey pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1991-01-01

    The molecular forms of proopiomelanocortin (POMC) derived amidated and C-terminal glycine-extended joining peptide from monkey (Macaca mulatta) pituitary were determined. The predominant forms of joining peptide found were the low molecular peptides POMC(76-105) and POMC(76-106), respectively...... sequence of monkey and human POMC extremely conserved, but also the processing patterns are similar. The monkey therefore serves as a suitable model for studying regulation of the processing of POMC and the hypothalamus-pituitary-adrenal axis in man....

  15. Evaluation of Trace Elements in Augmentation of Statin-Induced Cytotoxicity in Uremic Serum-Exposed Human Rhabdomyosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Hitoshi Uchiyama

    2018-01-01

    Full Text Available Patients with end-stage kidney disease (ESKD are at higher risk for rhabdomyolysis induced by statin than patients with normal kidney function. Previously, we showed that this increase in the severity of statin-induced rhabdomyolysis was partly due to uremic toxins. However, changes in the quantity of various trace elements in ESKD patients likely contribute as well. The purpose of this study is to determine the effect of trace elements on statin-induced toxicity in rhabdomyosarcoma cells exposed to uremic serum (US cells for a long time. Cell viability, apoptosis, mRNA expression, and intracellular trace elements were assessed by viability assays, flow cytometry, real-time RT-PCR, and ICP-MS, respectively. US cells exhibited greater simvastatin-induced cytotoxicity than cells long-time exposed with normal serum (NS cells (non-overlapping 95% confidence intervals. Intracellular levels of Mg, Mn, Cu, and Zn were significantly less in US cells compared to that in NS cells (p < 0.05 or 0.01. Pre-treatment with TPEN increased simvastatin-induced cytotoxicity and eliminated the distinction between both cells of simvastatin-induced cytotoxicity. These results suggest that Zn deficiencies may be involved in the increased risk for muscle complaints in ESKD patients. In conclusion, the increased severity of statin-induced rhabdomyolysis in ESKD patients may be partly due to trace elements deficiencies.

  16. Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to X-rays.

    Science.gov (United States)

    Varès, Guillaume; Wang, Bing; Tanaka, Kaoru; Kakimoto, Ayana; Eguchi-Kasai, Kyomi; Nenoi, Mitsuru

    2011-01-10

    The ability of cells to adapt low-dose or low-dose rate radiation is well known. High-LET radiation has unique characteristics, and the data concerning low doses effects and high-LET radiation remain fragmented. In this study, we assessed in vitro the ability of low doses of X-rays to induce an adaptive response (AR) to a subsequent challenging dose of heavy-ion radiation. Lymphoblastoid cells (TK6, AHH-1, NH32) were exposed to priming 0.02-0.1Gy X-rays, followed 6h later by challenging 1Gy heavy-ion radiation (carbon-ion: 20 and 40keV/μm, neon-ion: 150keV/μm). Pre-exposure of p53-competent cells resulted in decreased mutation frequencies at hypoxanthine-guanine phosphoribosyl transferase locus and different H2AX phosphorylation kinetics, as compared to cells exposed to challenging radiation alone. This phenomenon did not seem to be linked with cell cycle effects or radiation-induced apoptosis. Taken together, our results suggested the existence of an AR to mutagenic effects of heavy-ion radiation in lymphoblastoid cells and the involvement of double-strand break repair mechanisms. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Experimental study of the role of blocking of 5-HT3 serotonin receptors and D2 dophamin receptors in the mechanism of early radiation vomiting in monkeys

    International Nuclear Information System (INIS)

    Martirosov, K.S.; Grigor'ev, Yu.G.; Zorin, V.V.; Andrianova, I.E.

    2000-01-01

    Specific activity of Latranum and Dimetphramidum is studied using experimental model of early radiation vomiting on 17 monkeys, mass 6-9 kg inherent on usual ration of vivarium. The experiments with M. fasciculata monkeys exposed to 137 Cs γ-radiation with a dose of 6.9 Gy showed that Latranum, a blocker of serotonin 5-HT 3 receptors, is a more efficient antimetric than Dimetphramidum, a D 2 dophamin lytic. This suggested by fewer animals with emetic reaction of by less severe vomiting in case they have any. The results agree well with a hypothesis that serotonin receptors are dominant in the chemoreceptor trigger zone of monkeys [ru

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

    Science.gov (United States)

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

    2014-06-01

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

  19. Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys

    International Nuclear Information System (INIS)

    Doerge, Daniel R.; Twaddle, Nathan C.; Woodling, Kellie A.; Fisher, Jeffrey W.

    2010-01-01

    Bisphenol A (BPA) is a high-production volume industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 is controversial because of the potential for endocrine disruption, particularly during perinatal development, as suggested by in vitro, experimental animal, and epidemiological studies. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal rhesus monkeys by oral (PND 5, 35, 70) and intravenous injection (PND 77) routes using d6-BPA to avoid sample contamination. The concentration-time profiles observed in adult monkeys following oral administration of 100 μg/kg bw were remarkably similar to those previously reported in human volunteers given a similar dose; moreover, minimal pharmacokinetic differences were observed between neonatal and adult monkeys for the receptor-active aglycone form of BPA. Circulating concentrations of BPA aglycone were quite low following oral administration (< 1% of total), which reflects the redundancy of active UDP-glucuronosyl transferase isoforms in both gut and liver. No age-related changes were seen in internal exposure metrics for aglycone BPA in monkeys, a result clearly different from developing rats where significant inverse age-related changes, based on immaturity of Phase II metabolism and renal excretion, were recently reported. These observations imply that any toxicological effect observed in rats from early postnatal exposures to BPA could over-predict those possible in primates of the same age, based on significantly higher internal exposures and overall immaturity at birth.

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

    Science.gov (United States)

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

    2013-08-01

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

  1. Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL.

    Science.gov (United States)

    Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

    2013-01-01

    Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions.

  2. Specific Kv1.3 blockade modulates key cholesterol-metabolism-associated molecules in human macrophages exposed to ox-LDL[S

    Science.gov (United States)

    Yang, Yong; Wang, Yan-Fu; Yang, Xiao-Fang; Wang, Zhao-Hui; Lian, Yi-Tian; Yang, Ying; Li, Xiao-Wei; Gao, Xiang; Chen, Jian; Shu, Yan-Wen; Cheng, Long-Xian; Liao, Yu-Hua; Liu, Kun

    2013-01-01

    Cholesterol-metabolism-associated molecules, including scavenger receptor class A (SR-A), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), CD36, ACAT1, ABCA1, ABCG1, and scavenger receptor class B type I, can modulate cholesterol metabolism in the transformation from macrophages to foam cells. Voltage-gated potassium channel Kv1.3 has increasingly been demonstrated to play an important role in the modulation of macrophage function. Here, we investigate the role of Kv1.3 in modulating cholesterol-metabolism-associated molecules in human acute monocytic leukemia cell-derived macrophages (THP-1 macrophages) and human monocyte-derived macrophages exposed to oxidized LDL (ox-LDL). Human Kv1.3 and Kv1.5 channels (hKv1.3 and hKv1.5) are expressed in macrophages and form a heteromultimeric channel. The hKv1.3-E314 antibody that we had generated as a specific hKv1.3 blocker inhibited outward delayed rectifier potassium currents, whereas the hKv1.5-E313 antibody that we had generated as a specific hKv1.5 blocker failed. Accordingly, the hKv1.3-E314 antibody reduced percentage of cholesterol ester and enhanced apoA-I-mediated cholesterol efflux in THP-1 macrophages and human monocyte-derived macrophages exposed to ox-LDL. The hKv1.3-E314 antibody downregulated SR-A, LOX-1, and ACAT1 expression and upregulated ABCA1 expression in THP-1 macrophages and human monocyte-derived macrophages. Our results reveal that specific Kv1.3 blockade represents a novel strategy modulating cholesterol metabolism in macrophages, which benefits the treatment of atherosclerotic lesions. PMID:23099443

  3. Punicalagin and (-)-Epigallocatechin-3-Gallate Rescue Cell Viability and Attenuate Inflammatory Responses of Human Epidermal Keratinocytes Exposed to Airborne Particulate Matter PM10.

    Science.gov (United States)

    Seok, Jin Kyung; Lee, Jeong-Won; Kim, Young Mi; Boo, Yong Chool

    2018-01-01

    Airborne particulate matter with a diameter of < 10 µm (PM10) causes oxidative damage, inflammation, and premature skin aging. In this study, we evaluated whether polyphenolic antioxidants attenuate the inflammatory responses of PM10-exposed keratinocytes. Primary human epidermal keratinocytes were exposed in vitro to PM10 in the absence or presence of punicalagin and (-)-epigallocatechin-3-gallate (EGCG), which are the major polyphenolic antioxidants found in pomegranate and green tea, respectively. Assays were performed to determine cell viability, production of reactive oxygen species (ROS), and expression of NADPH oxidases (NOX), proinflammatory cytokines, and matrix metalloproteinase (MMP)-1. PM10 decreased cell viability and increased ROS production in a dose-dependent manner. It also increased the expression levels of NOX-1, NOX-2, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, and MMP-1. Punicalagin was not cytotoxic up to 300 μM, and (-)-EGCG was cytotoxic above 30 μM, respectively. Further, punicalagin (3-30 μM) and EGCG (3-10 μM) rescued the viability of PM10-exposed cells. They also attenuated ROS production and the expression of NOX-1, NOX-2, TNF-α, IL-1β, IL-6, IL-8, and MMP-1 stimulated by PM10. This study demonstrates that polyphenolic antioxidants, such as punicalagin and (-)-EGCG, rescue keratinocyte viability and attenuate the inflammatory responses of these cells due to airborne particles. © 2018 S. Karger AG, Basel.

  4. Enhancement of cell death by TNF α-related apoptosis-inducing ligand (TRAIL) in human lung carcinoma A549 cells exposed to X rays under hypoxia

    International Nuclear Information System (INIS)

    Takahashi, Momoko; Inanami, Osamu; Yasui, Hironobu; Ogura, Aki; Kuwabara, Mikinori; Kubota, Nobuo; Tsujitani, Michihiko

    2007-01-01

    Our previous study showed that ionizing radiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines and that the death receptor of the TNF α-related apoptosis-inducing ligand TRAIL enhanced the apoptotic pathway (Hamasu et al., (2005) Journal of Radiation Research, 46:103-110). The present experiments were performed to examine whether treatment with TRAIL enhanced the cell killing in tumor cells exposed to ionizing radiation under hypoxia, since the presence of radioresistant cells in hypoxic regions of solid tumors is a serious problem in radiation therapy for tumors. When human lung carcinoma A549 cells were irradiated under normoxia and hypoxia, respectively, radiation-induced enhancement of expression of DR5 was observed under both conditions. Incubation in the presence of TRAIL enhanced the caspase-dependent and chymotrypsin-like-protease-dependent apoptotic cell death in A549 cells exposed to X rays. Furthermore, it was shown that treatment with TRAIL enhanced apoptotic cell death and loss of clonogenic ability in A549 cells exposed to X rays not only under normoxia but also under hypoxia, suggesting that combination treatment with TRAIL and X irradiation is effective for hypoxic tumor cells. (author)

  5. Salmonella infections in Antarctic fauna and island populations of wildlife exposed to human activities in coastal areas of Australia.

    Science.gov (United States)

    Iveson, J B; Shellam, G R; Bradshaw, S D; Smith, D W; Mackenzie, J S; Mofflin, R G

    2009-06-01

    Salmonella infections in Antarctic wildlife were first reported in 1970 and in a search for evidence linking isolations with exposure to human activities, a comparison was made of serovars reported from marine fauna in the Antarctic region from 1982-2004 with those from marine mammals in the Northern hemisphere. This revealed that 10 (83%) Salmonella enterica serovars isolated from Antarctic penguins and seals were classifiable in high-frequency (HF) quotients for serovars prevalent in humans and domesticated animals. In Australia, 16 (90%) HF serovars were isolated from marine birds and mammals compared with 12 (86%) HF serovars reported from marine mammals in the Northern hemisphere. In Western Australia, HF serovars from marine species were also recorded in humans, livestock, mussels, effluents and island populations of wildlife in urban coastal areas. Low-frequency S. enterica serovars were rarely detected in humans and not detected in seagulls or marine species. The isolation of S. Enteritidis phage type 4 (PT4), PT8 and PT23 strains from Adélie penguins and a diversity of HF serovars reported from marine fauna in the Antarctic region and coastal areas of Australia, signal the possibility of transient serovars and endemic Salmonella strains recycling back to humans from southern latitudes in marine foodstuffs and feed ingredients.

  6. Post-exposure rabies prophylaxis in humans exposed to animals in Lublin province (Eastern Poland) in 2012-2015 - A retrospective study.

    Science.gov (United States)

    Krzowska-Firych, Joanna; Tomasiewicz, Krzysztof; Kozøowska, Agata

    2017-06-03

    Rabies continues to be one of the most important viral diseases and remains a significant threat to public health across the globe. The post-exposure prophylaxis in humans can effectively prevent death after exposure to a potentially infected animal. In Poland, recommendations for rabies PEP followed the national guidelines which recommend that people should receive PEP when bitten by an animal suspected to be infected by rabies. PEP in humans includes cleansing and disinfecting the wound or point of contact, and administering anti-rabies immunization. Rabies vaccine should be given for contacts of category II and category III exposures. RIG should be given for category III contact. The vaccination schedule includes 5 doses given within a 30 day period (the Essen regimen). The aim of our study was to determine the frequency of post-exposure prophylaxis among patients exposed to animals and also to assess the animal species suspected as a source of rabies exposure. We have retrospectively analyzed medical records from the years 2012-2015 of all adult patients who were exposed to animals and consulted at the Dispensary of Rabies Prophylaxis in the Department of Infectious Diseases at the Medical University in Lublin, Poland. All consulted patients were asked to give an informed consent in case of decision to use collected data for future research work. Ethical approval was obtained from the Ethics Committee of the Medical University of Lublin, Poland, and all patients included in this study gave an informed consent during consultation after the exposure to animals. During the studied 4-year period, 511 persons exposed to animals were consulted and prophylactic procedure consisting of active immunization were applied in 54.2% of the total consulted. Dogs and cats were the most common animal species suspected as the source of the rabies exposure. Anti-rabies prophylaxis was applied in 45.8% of all vaccinated patients exposed to dogs, and in 24.2% exposed to cats. All

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Visitor effect on the behavior of a group of spider monkeys (Ateles geoffroyi) maintained at an island in Lake Catemaco, Veracruz/Mexico.

    Science.gov (United States)

    Pérez-Galicia, Sergio; Miranda-Anaya, Manuel; Canales-Espinosa, Domingo; Muñoz-Delgado, Jairo

    2017-12-01

    We analyzed the effect of human visitors on the behavior of a group of spider monkeys (Ateles geoffroyi) kept on a small tourist island. Although the spider monkey is a common species in zoos, there are very few specific studies on visitor effects on these monkeys. We conducted behavioral observations on the group of spider monkeys to evaluate the effect of visitors. We also used actimetry devices to measure the variations in the spider monkeys' locomotor activity associated with human presence. With regard to the effect on behavior, we found an increase in self-directed behaviors and a decrease in vocalization, both associated with human presence. Moreover, our results suggest that when people feed monkeys, there is an increase in agonistic behaviors. On the other hand, we found that changes in activity levels in response to human presence vary among individuals. We conclude that changes in spider monkeys' behavior could provide evidence of the negative effect of visitors in our study conditions. Although we discuss the differences in activity levels due to differences in social position, further research is required this topic. Our results can be used to inform management plans for this species in captivity. Improving this relationship between humans and non-human primates through tourism education programs would benefit ecotourism and therefore species conservation programs. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2017-07-21

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

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

    Science.gov (United States)

    Sharp, Lesley A

    2017-06-01

    Why do lab monkeys watch TV? This essay examines the preponderance of televisions in primate housing units based in academic research laboratories. Within such labs, television and related visual media are glossed as part-and-parcel of welfare or species-specific enrichment practices intended for research monkeys, a logic that is simultaneously historically- and ontologically-based. In many research centers, television figures prominently in the two inseparable domains of a lab monkey's life: as a research tool employed during experiments, and in housing units where captive monkeys are said to enjoy watching TV during "down time." My purpose is not to determine whether monkeys do indeed enjoy, or need, television; rather, I employ visual media as a means to uncover, and decipher, the moral logic of an ethics of care directed specifically at highly sentient creatures who serve as human proxies in a range of experimental contexts. I suggest that this specialized ethics of animal care materializes Mattingly's notion of "moral laboratories" (Mattingly in Moral laboratories: family peril and the struggle for a good life, University of California Press, Berkeley, 2014), where television mediates the troublesome boundary of species difference among the simian and human subjects who cohabit laboratory worlds.

  11. Analysis of 62 hybrid assembled human Y chromosomes exposes rapid structural changes and high rates of gene conversion

    DEFF Research Database (Denmark)

    Gonzalez-Izarzugaza, Jose Maria; Skov, Laurits; Maretty, Lasse

    2017-01-01

    The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats and the po......The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats...... and the potentially large role of gene conversion. Here we perform an evolutionary analysis of 62 Y-chromosomes of Danish descent sequenced using a wide range of library insert sizes and high coverage, thus allowing large regions of these chromosomes to be well assembled. These include 17 father-son pairs, which we...... use to validate variation calling. Using a recent method that can integrate variants based on both mapping and de novo assembly, we genotype 10898 SNVs and 2903 indels (max length of 27241 bp) in our sample and show by father-son concordance and experimental validation that the non-recurrent SNP...

  12. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jaguin, Marie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex (France); Lecureur, Valérie, E-mail: valerie.lecureur@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France)

    2015-06-15

    Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.

  13. Giardia duodenalis and Cryptosporidium occurrence in Australian sea lions (Neophoca cinerea) exposed to varied levels of human interaction.

    Science.gov (United States)

    Delport, Tiffany C; Asher, Amy J; Beaumont, Linda J; Webster, Koa N; Harcourt, Robert G; Power, Michelle L

    2014-12-01

    Giardia and Cryptosporidium are amongst the most common protozoan parasites identified as causing enteric disease in pinnipeds. A number of Giardia assemblages and Cryptosporidium species and genotypes are common in humans and terrestrial mammals and have also been identified in marine mammals. To investigate the occurrence of these parasites in an endangered marine mammal, the Australian sea lion (Neophoca cinerea), genomic DNA was extracted from faecal samples collected from wild populations (n = 271) in Southern and Western Australia and three Australian captive populations (n = 19). These were screened using PCR targeting the 18S rRNA of Giardia and Cryptosporidium. Giardia duodenalis was detected in 28 wild sea lions and in seven captive individuals. Successful sequencing of the 18S rRNA gene assigned 27 Giardia isolates to assemblage B and one to assemblage A, both assemblages commonly found in humans. Subsequent screening at the gdh and β-giardin loci resulted in amplification of only one of the 35 18S rRNA positive samples at the β-giardin locus. Sequencing at the β-giardin locus assigned the assemblage B 18S rRNA confirmed isolate to assemblage AI. The geographic distribution of sea lion populations sampled in relation to human settlements indicated that Giardia presence in sea lions was highest in populations less than 25 km from humans. Cryptosporidium was not detected by PCR screening in either wild colonies or captive sea lion populations. These data suggest that the presence of G. duodenalis in the endangered Australian sea lion is likely the result of dispersal from human sources. Multilocus molecular analyses are essential for the determination of G. duodenalis assemblages and subsequent inferences on transmission routes to endangered marine mammal populations.