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  1. Functional analysis of human and chimpanzee promoters.

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    Heissig, Florian; Krause, Johannes; Bryk, Jaroslaw; Khaitovich, Philipp; Enard, Wolfgang; Pääbo, Svante

    2005-01-01

    It has long been argued that changes in gene expression may provide an additional and crucial perspective on the evolutionary differences between humans and chimpanzees. To investigate how often expression differences seen in tissues are caused by sequence differences in the proximal promoters, we tested the expression activity in cultured cells of human and chimpanzee promoters from genes that differ in mRNA expression between human and chimpanzee tissues. Twelve promoters for which the corresponding gene had been shown to be differentially expressed between humans and chimpanzees in liver or brain were tested. Seven showed a significant difference in activity between the human promoter and the orthologous chimpanzee promoter in at least one of the two cell lines used. However, only three of them showed a difference in the same direction as in the tissues. Differences in proximal promoter activity are likely to be common between humans and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This suggests that several genetic differences between humans and chimpanzees might be responsible for a single expression difference and thus that relevant expression differences between humans and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.

  2. Translating chimpanzee personality to humans: Investigating the transportability of chimpanzee-derived personality scales to humans.

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    Latzman, Robert D; Sauvigné, Katheryn C; Hopkins, William D

    2016-06-01

    There is a growing interest in the study of personality in chimpanzees with repeated findings of a similar structure of personality in apes to that found in humans. To date, however, the direct translational value of instruments used to assess chimpanzee personality to humans has yet to be explicitly tested. As such, in the current study we sought to determine the transportability of factor analytically-derived chimpanzee personality scales to humans in a large human sample (N = 301). Human informants reporting on target individuals they knew well completed chimpanzee-derived and human-derived measures of personality from the two most widely studied models of human personality: Big Five and Big Three. The correspondence between informant-reported chimpanzee- and human-derived personality scales was then investigated. Results indicated high convergence for corresponding scales across most chimpanzee- and human-derived personality scales. Findings from the current study provide evidence that chimpanzee-derived scales translate well to humans and operate quite similarly to the established human-derived personality scales in a human sample. This evidence of transportability lends support to the translational nature of chimpanzee personality research suggesting clear relevance of this growing literature to humans. Am. J. Primatol. 78:601-609, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  3. Challenge Pools of Hepatitis C Virus Genotypes 1–6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver–Chimeric Mouse Models

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    Bukh, Jens; Meuleman, Philip; Tellier, Raymond; Engle, Ronald E.; Feinstone, Stephen M.; Eder, Gerald; Satterfield, William C.; Govindarajan, Sugantha; Krawczynski, Krzysztof; Miller, Roger H.; Leroux-Roels, Geert; Purcell, Robert H.

    2010-01-01

    Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1–6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >104.7 IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 103–105 chimpanzee infectious doses/mL. Human liver–chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1–6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo. PMID:20353362

  4. Human faces are slower than chimpanzee faces.

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    Anne M Burrows

    Full Text Available While humans (like other primates communicate with facial expressions, the evolution of speech added a new function to the facial muscles (facial expression muscles. The evolution of speech required the development of a coordinated action between visual (movement of the lips and auditory signals in a rhythmic fashion to produce "visemes" (visual movements of the lips that correspond to specific sounds. Visemes depend upon facial muscles to regulate shape of the lips, which themselves act as speech articulators. This movement necessitates a more controlled, sustained muscle contraction than that produced during spontaneous facial expressions which occur rapidly and last only a short period of time. Recently, it was found that human tongue musculature contains a higher proportion of slow-twitch myosin fibers than in rhesus macaques, which is related to the slower, more controlled movements of the human tongue in the production of speech. Are there similar unique, evolutionary physiologic biases found in human facial musculature related to the evolution of speech?Using myosin immunohistochemistry, we tested the hypothesis that human facial musculature has a higher percentage of slow-twitch myosin fibers relative to chimpanzees (Pan troglodytes and rhesus macaques (Macaca mulatta. We sampled the orbicularis oris and zygomaticus major muscles from three cadavers of each species and compared proportions of fiber-types. Results confirmed our hypothesis: humans had the highest proportion of slow-twitch myosin fibers while chimpanzees had the highest proportion of fast-twitch fibers.These findings demonstrate that the human face is slower than that of rhesus macaques and our closest living relative, the chimpanzee. They also support the assertion that human facial musculature and speech co-evolved. Further, these results suggest a unique set of evolutionary selective pressures on human facial musculature to slow down while the function of this muscle

  5. Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

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    Bukh, Jens; Meuleman, Philip; Tellier, Raymond

    2010-01-01

    Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional a...

  6. Origins of De Novo Genes in Human and Chimpanzee.

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    Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M Mar

    2015-12-01

    The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species--human, chimpanzee, macaque, and mouse--and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.

  7. Technical intelligence and culture: Nut cracking in humans and chimpanzees.

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    Boesch, Christophe; Bombjaková, Daša; Boyette, Adam; Meier, Amelia

    2017-06-01

    According to the technical intelligence hypothesis, humans are superior to all other animal species in understanding and using tools. However, the vast majority of comparative studies between humans and chimpanzees, both proficient tool users, have not controlled for the effects of age, prior knowledge, past experience, rearing conditions, or differences in experimental procedures. We tested whether humans are superior to chimpanzees in selecting better tools, using them more dexteriously, achieving higher performance and gaining access to more resource as predicted under the technical intelligence hypothesis. Aka and Mbendjele hunter-gatherers in the rainforest of Central African Republic and the Republic of Congo, respectively, and Taï chimpanzees in the rainforest of Côte d'Ivoire were observed cracking hard Panda oleosa nuts with different tools, as well as the soft Coula edulis and Elaeis guinensis nuts. The nut-cracking techniques, hammer material selection and two efficiency measures were compared. As predicted, the Aka and the Mbendjele were able to exploit more species of hard nuts in the forest than chimpanzees. However, the chimpanzees were sometimes more efficient than the humans. Social roles differed between the two species, with the Aka and especially the Mbendjele exhibiting cooperation between nut-crackers whereas the chimpanzees were mainly individualistic. Observations of nut-cracking by humans and chimpanzees only partially supported the technical intelligence hypothesis as higher degrees of flexibility in tool selection seen in chimpanzees compensated for use of less efficient tool material than in humans. Nut cracking was a stronger social undertaking in humans than in chimpanzees. © 2017 Wiley Periodicals, Inc.

  8. The bonobo genome compared with the chimpanzee and human genomes

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    Prüfer, Kay; Munch, Kasper; Hellmann, Ines; Akagi, Keiko; Miller, Jason R.; Walenz, Brian; Koren, Sergey; Sutton, Granger; Kodira, Chinnappa; Winer, Roger; Knight, James R.; Mullikin, James C.; Meader, Stephen J.; Ponting, Chris P.; Lunter, Gerton; Higashino, Saneyuki; Hobolth, Asger; Dutheil, Julien; Karakoç, Emre; Alkan, Can; Sajjadian, Saba; Catacchio, Claudia Rita; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Junhold, Jörg; Patterson, Nick; Siebauer, Michael; Good, Jeffrey M.; Fischer, Anne; Ptak, Susan E.; Lachmann, Michael; Symer, David E.; Mailund, Thomas; Schierup, Mikkel H.; Andrés, Aida M.; Kelso, Janet; Pääbo, Svante

    2012-01-01

    Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours1–4, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. PMID:22722832

  9. Wild Cultures: A Comparison between Chimpanzee and Human Cultures

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    Diana Rocío Carvajal Contreras

    2013-07-01

    Full Text Available Review of Wild Cultures: A Comparison between Chimpanzee and Human Cultures. Christophe Boesch. 2012. Cambridge University Press. Pp. 276, 68 b & w illustrations, 11 tables. £60 (hardback. ISBN 9781109025370.

  10. Comparative rates of violence in chimpanzees and humans.

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    Wrangham, Richard W; Wilson, Michael L; Muller, Martin N

    2006-01-01

    This paper tests the proposal that chimpanzees (Pan troglodytes) and humans have similar rates of death from intraspecific aggression, whereas chimpanzees have higher rates of non-lethal physical attack (Boehm 1999, Hierarchy in the forest: the evolution of egalitarian behavior. Harvard University Press). First, we assembled data on lethal aggression from long-term studies of nine communities of chimpanzees living in five populations. We calculated rates of death from intraspecific aggression both within and between communities. Variation among communities in mortality rates from aggression was high, and rates of death from intercommunity and intracommunity aggression were not correlated. Estimates for average rates of lethal violence for chimpanzees proved to be similar to average rates for subsistence societies of hunter-gatherers and farmers. Second, we compared rates of non-lethal physical aggression for two populations of chimpanzees and one population of recently settled hunter-gatherers. Chimpanzees had rates of aggression between two and three orders of magnitude higher than humans. These preliminary data support Boehm's hypothesis.

  11. Can Chimpanzee Biology Highlight Human Origin and Evolution?

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    Itai Roffman

    2010-07-01

    Full Text Available The closest living relatives of humans are their chimpanzee/bonobo (Pan sister species, members of the same subfamily “Homininae”. This classification is supported by over 50 years of research in the fields of chimpanzee cultural diversity, language competency, genomics, anatomy, high cognition, psychology, society, self-consciousness and relation to others, tool use/production, as well as Homo level emotions, symbolic competency, memory recollection, complex multifaceted problem-solving capabilities, and interspecies communication. Language competence and symbolism can be continuously bridged from chimpanzee to man. Emotions, intercommunity aggression, body language, gestures, facial expressions, and vocalization of intonations seem to parallel between the sister taxa Homo and Pan. The shared suite of traits between Pan and Homo genus demonstrated in this article integrates old and new information on human–chimpanzee evolution, bilateral informational and cross-cultural exchange, promoting the urgent need for Pan cultures in the wild to be protected, as they are part of the cultural heritage of mankind. Also, we suggest that bonobos, Pan paniscus, based on shared traits with Australopithecus, need to be included in Australopithecine’s subgenus, and may even represent living-fossil Australopithecines. Unfolding bonobo and chimpanzee biology highlights our common genetic and cultural evolutionary origins.

  12. Spatial Construction Skills of Chimpanzees ("Pan Troglodytes") and Young Human Children ("Homo Sapiens Sapiens")

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    Poti, Patrizia; Hayashi, Misato; Matsuzawa, Tetsuro

    2009-01-01

    Spatial construction tasks are basic tests of visual-spatial processing. Two studies have assessed spatial construction skills in chimpanzees (Pan troglodytes) and young children (Homo sapiens sapiens) with a block modelling task. Study 1a subjects were three young chimpanzees and five adult chimpanzees. Study 1b subjects were 30 human children…

  13. Ontogenetic trajectories of chimpanzee social play: similarities with humans.

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    Giada Cordoni

    Full Text Available Social play, a widespread phenomenon in mammals, is a multifunctional behavior, which can have many different roles according to species, sex, age, relationship quality between playmates, group membership, context, and habitat. Play joins and cuts across a variety of disciplines leading directly to inquiries relating to individual developmental changes and species adaptation, thus the importance of comparative studies appears evident. Here, we aim at proposing a possible ontogenetic pathway of chimpanzee play (Pan troglodytes and contrast our data with those of human play. Chimpanzee play shows a number of changes from infancy to juvenility. Particularly, solitary and social play follows different developmental trajectories. While solitary play peaks in infancy, social play does not show any quantitative variation between infancy and juvenility but shows a strong qualitative variation in complexity, asymmetry, and playmate choice. Like laughter in humans, the playful expressions in chimpanzees (at the different age phases seem to have a role in advertising cooperative dispositions and intentions thus increasing the likelihood of engaging in solid social relationships. In conclusion, in chimpanzees, as in humans, both play behavior and the signals that accompany play serve multiple functions according to the different age phases.

  14. Human children rely more on social information than chimpanzees do.

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    van Leeuwen, Edwin J C; Call, Josep; Haun, Daniel B M

    2014-11-01

    Human societies are characterized by more cultural diversity than chimpanzee communities. However, it is currently unclear what mechanism might be driving this difference. Because reliance on social information is a pivotal characteristic of culture, we investigated individual and social information reliance in children and chimpanzees. We repeatedly presented subjects with a reward-retrieval task on which they had collected conflicting individual and social information of equal accuracy in counterbalanced order. While both species relied mostly on their individual information, children but not chimpanzees searched for the reward at the socially demonstrated location more than at a random location. Moreover, only children used social information adaptively when individual knowledge on the location of the reward had not yet been obtained. Social information usage determines information transmission and in conjunction with mechanisms that create cultural variants, such as innovation, it facilitates diversity. Our results may help explain why humans are more culturally diversified than chimpanzees. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  15. Bayesian inference of shared recombination hotspots between humans and chimpanzees.

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    Wang, Ying; Rannala, Bruce

    2014-12-01

    Recombination generates variation and facilitates evolution. Recombination (or lack thereof) also contributes to human genetic disease. Methods for mapping genes influencing complex genetic diseases via association rely on linkage disequilibrium (LD) in human populations, which is influenced by rates of recombination across the genome. Comparative population genomic analyses of recombination using related primate species can identify factors influencing rates of recombination in humans. Such studies can indicate how variable hotspots for recombination may be both among individuals (or populations) and over evolutionary timescales. Previous studies have suggested that locations of recombination hotspots are not conserved between humans and chimpanzees. We made use of the data sets from recent resequencing projects and applied a Bayesian method for identifying hotspots and estimating recombination rates. We also reanalyzed SNP data sets for regions with known hotspots in humans using samples from the human and chimpanzee. The Bayes factors (BF) of shared recombination hotspots between human and chimpanzee across regions were obtained. Based on the analysis of the aligned regions of human chromosome 21, locations where the two species show evidence of shared recombination hotspots (with high BFs) were identified. Interestingly, previous comparative studies of human and chimpanzee that focused on the known human recombination hotspots within the β-globin and HLA regions did not find overlapping of hotspots. Our results show high BFs of shared hotspots at locations within both regions, and the estimated locations of shared hotspots overlap with the locations of human recombination hotspots obtained from sperm-typing studies. Copyright © 2014 by the Genetics Society of America.

  16. Chimpanzees and humans mimic pupil-size of conspecifics.

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    Mariska E Kret

    Full Text Available Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes. We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals.

  17. Rates of genomic divergence in humans, chimpanzees and their lice.

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    Johnson, Kevin P; Allen, Julie M; Olds, Brett P; Mugisha, Lawrence; Reed, David L; Paige, Ken N; Pittendrigh, Barry R

    2014-02-22

    The rate of DNA mutation and divergence is highly variable across the tree of life. However, the reasons underlying this variation are not well understood. Comparing the rates of genetic changes between hosts and parasite lineages that diverged at the same time is one way to begin to understand differences in genetic mutation and substitution rates. Such studies have indicated that the rate of genetic divergence in parasites is often faster than that of their hosts when comparing single genes. However, the variation in this relative rate of molecular evolution across different genes in the genome is unknown. We compared the rate of DNA sequence divergence between humans, chimpanzees and their ectoparasitic lice for 1534 protein-coding genes across their genomes. The rate of DNA substitution in these orthologous genes was on average 14 times faster for lice than for humans and chimpanzees. In addition, these rates were positively correlated across genes. Because this correlation only occurred for substitutions that changed the amino acid, this pattern is probably produced by similar functional constraints across the same genes in humans, chimpanzees and their ectoparasites.

  18. Comprehension of iconic gestures by chimpanzees and human children.

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    Bohn, Manuel; Call, Josep; Tomasello, Michael

    2016-02-01

    Iconic gestures-communicative acts using hand or body movements that resemble their referent-figure prominently in theories of language evolution and development. This study contrasted the abilities of chimpanzees (N=11) and 4-year-old human children (N=24) to comprehend novel iconic gestures. Participants learned to retrieve rewards from apparatuses in two distinct locations, each requiring a different action. In the test, a human adult informed the participant where to go by miming the action needed to obtain the reward. Children used the iconic gestures (more than arbitrary gestures) to locate the reward, whereas chimpanzees did not. Some children also used arbitrary gestures in the same way, but only after they had previously shown comprehension for iconic gestures. Over time, chimpanzees learned to associate iconic gestures with the appropriate location faster than arbitrary gestures, suggesting at least some recognition of the iconicity involved. These results demonstrate the importance of iconicity in referential communication. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Different Social Motives in the Gestural Communication of Chimpanzees and Human Children

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    Bullinger, Anke F.; Zimmermann, Felizitas; Kaminski, Juliane; Tomasello, Michael

    2011-01-01

    Both chimpanzees and human infants use the pointing gesture with human adults, but it is not clear if they are doing so for the same social motives. In two studies, we presented chimpanzees and human 25-month-olds with the opportunity to point for a hidden tool (in the presence of a non-functional distractor). In one condition it was clear that…

  20. Incomplete lineage sorting patterns among human, chimpanzee and orangutan suggest recent orangutan speciation and widespread selection

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    Hobolth, Asger; Dutheil, Julien; Hawks, John

    2011-01-01

    We search the complete orangutan genome for regions where humans are more closely related to orangutans than to chimpanzees due to incomplete lineage sorting (ILS) in the ancestor of human and chimpanzees. The search uses our recently developed coalescent HMM framework. We find ILS present in ~1%...

  1. Morphological integration in the gorilla, chimpanzee, and human neck.

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    Arlegi, Mikel; Gómez-Robles, Aida; Gómez-Olivencia, Asier

    2018-06-01

    Although integration studies are important to understand the evolution of organisms' traits across phylogenies, vertebral integration in primates is still largely unexplored. Here we describe and quantify patterns of morphological integration and modularity in the subaxial cervical vertebrae (C3-C7) in extant hominines incorporating the potential influence of size. Three-dimensional landmarks were digitized on 546 subaxial cervical vertebrae from 141 adult individuals of Gorilla gorilla, Pan troglodytes, and Homo sapiens. Integration and modularity, and the influence of size effects, were quantified using geometric morphometric approaches. All subaxial cervical vertebrae from the three species show a strong degree of integration. Gorillas show the highest degree of integration; conversely, humans have the lowest degree of integration. Analyses of allometric regression residuals show that size is an important factor promoting integration in gorillas, with lesser influence in chimpanzees and almost no effect in humans. Results point to a likely ancestral pattern of integration in non-human hominines, whereby the degree of integration decreases from cranial to caudal positions. Humans deviate from this pattern in the cranialmost (C3) and, to a lesser extent, in the caudalmost (C7) vertebrae, which are less integrated. These differences can be tentatively related to the emergence of bipedalism due to the presence of modern human-like C3 in australopiths, which still preserve a more chimpanzee-like C7. © 2018 Wiley Periodicals, Inc.

  2. Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

    DEFF Research Database (Denmark)

    Hoof, Ilka; Kesmir, Can; Lund, Ole

    2008-01-01

    and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors. Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities...... in their MHC class I repertoire. Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs...... with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control....

  3. Probable transmission of coxsackie B3 virus from human to chimpanzee, Denmark

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    Nielsen, Sandra Cathrine Abel; Mourier, Tobias; Baandrup, Ulrik

    2012-01-01

    In 2010, a chimpanzee died at Copenhagen Zoo following an outbreak of respiratory disease among chimpanzees in the zoo. Identification of coxsackie B3 virus, a common human pathogen, as the causative agent, and its severe manifestation, raise questions about pathogenicity and transmissibility among...

  4. 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.

  5. Human fibroblasts display a differential focal adhesion phenotype relative to chimpanzee.

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    Advani, Alexander S; Chen, Annie Y; Babbitt, Courtney C

    2016-01-01

    There are a number of documented differences between humans and our closest relatives in responses to wound healing and in disease susceptibilities, suggesting a differential cellular response to certain environmental factors. In this study, we sought to look at a specific cell type, fibroblasts, to examine differences in cellular adhesion between humans and chimpanzees in visualized cells and in gene expression. We have found significant differences in the number of focal adhesions between primary human and chimpanzee fibroblasts. Additionally, we see that adhesion related gene ontology categories are some of the most differentially expressed between human and chimpanzee in normal fibroblast cells. These results suggest that human and chimpanzee fibroblasts may have somewhat different adhesive properties, which could play a role in differential disease phenotypes and responses to external factors. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  6. Favorable ecological circumstances promote life expectancy in chimpanzees similar to that of human hunter-gatherers.

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    Wood, Brian M; Watts, David P; Mitani, John C; Langergraber, Kevin E

    2017-04-01

    Demographic data on wild chimpanzees are crucial for understanding the evolution of chimpanzee and hominin life histories, but most data come from populations affected by disease outbreaks and anthropogenic disturbance. We present survivorship data from a relatively undisturbed and exceptionally large community of eastern chimpanzees (Pan troglodytes schweinfurthii) at Ngogo, Kibale National Park, Uganda. We monitored births, deaths, immigrations, and emigrations in the community between 1995 and 2016. Using known and estimated ages, we calculated survivorship curves for the whole community, for males and females separately, and for individuals ≤2 years old when identified. We used a novel method to address age estimation error by calculating stochastic survivorship curves. We compared Ngogo life expectancy, survivorship, and mortality rates to those from other chimpanzee communities and human hunter-gatherers. Life expectancy at birth for both sexes combined was 32.8 years, far exceeding estimates of chimpanzee life expectancy in other communities, and falling within the range of human hunter-gatherers (i.e., 27-37 years). Overall, the pattern of survivorship at Ngogo was more similar to that of human hunter-gatherers than to other chimpanzee communities. Maximum lifespan for the Ngogo chimpanzees, however, was similar to that reported at other chimpanzee research sites and was less than that of human-hunter gatherers. The absence of predation by large carnivores may contribute to some of the higher survivorship at Ngogo, but this cannot explain the much higher survivorship at Ngogo than at Kanyawara, another chimpanzee community in the same forest, which also lacks large carnivores. Higher survivorship at Ngogo appears to be an adaptive response to a food supply that is more abundant and varies less than that of Kanyawara. Future analyses of hominin life history evolution should take these results into account. Copyright © 2017 Elsevier Ltd. All rights

  7. Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees.

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    Chabot, Adrien; Shrit, Ralla A; Blekhman, Ran; Gilad, Yoav

    2007-08-01

    Most phenotypic differences between human and chimpanzee are likely to result from differences in gene regulation, rather than changes to protein-coding regions. To date, however, only a handful of human-chimpanzee nucleotide differences leading to changes in gene regulation have been identified. To hone in on differences in regulatory elements between human and chimpanzee, we focused on 10 genes that were previously found to be differentially expressed between the two species. We then designed reporter gene assays for the putative human and chimpanzee promoters of the 10 genes. Of seven promoters that we found to be active in human liver cell lines, human and chimpanzee promoters had significantly different activity in four cases, three of which recapitulated the gene expression difference seen in the microarray experiment. For these three genes, we were therefore able to demonstrate that a change in cis influences expression differences between humans and chimpanzees. Moreover, using site-directed mutagenesis on one construct, the promoter for the DDA3 gene, we were able to identify three nucleotides that together lead to a cis regulatory difference between the species. High-throughput application of this approach can provide a map of regulatory element differences between humans and our close evolutionary relatives.

  8. Innate Immune Responses to TLR2 and TLR4 Agonists Differ between Baboons, Chimpanzees and Humans

    Science.gov (United States)

    Brinkworth, Jessica F.; Pechenkina, Ekaterina A.; Silver, Jack; Goyert, Sanna M.

    2012-01-01

    Background African catarrhine primates differ in bacterial disease susceptibility. Methods Human, chimpanzee, and baboon blood was stimulated with TLR-detected bacterial agonists and cytokine/chemokine induction assessed by real-time pcr. Results Humans and chimpanzees shared similar cytokine/chemokine responses, while baboon cytokine/chemokine induction differed. Generally, responses were agonist-independent. Conclusions These primates tend to generate species rather than agonist–specific responses to bacterial agonists. PMID:22978822

  9. Bonobos and chimpanzees exhibit human-like framing effects

    Science.gov (United States)

    Krupenye, Christopher; Rosati, Alexandra G.; Hare, Brian

    2015-01-01

    Humans exhibit framing effects when making choices, appraising decisions involving losses differently from those involving gains. To directly test for the evolutionary origin of this bias, we examined decision-making in humans' closest living relatives: bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). We presented the largest sample of non-humans to date (n = 40) with a simple task requiring minimal experience. Apes made choices between a ‘framed’ option that provided preferred food, and an alternative option that provided a constant amount of intermediately preferred food. In the gain condition, apes experienced a positive ‘gain’ event in which the framed option was initially presented as one piece of food but sometimes was augmented to two. In the loss condition, apes experienced a negative ‘loss' event in which they initially saw two pieces but sometimes received only one. Both conditions provided equal pay-offs, but apes chose the framed option more often in the positive ‘gain’ frame. Moreover, male apes were more susceptible to framing than were females. These results suggest that some human economic biases are shared through common descent with other apes and highlight the importance of comparative work in understanding the origins of individual differences in human choice. PMID:25672997

  10. Bonobos and chimpanzees exhibit human-like framing effects.

    Science.gov (United States)

    Krupenye, Christopher; Rosati, Alexandra G; Hare, Brian

    2015-02-01

    Humans exhibit framing effects when making choices, appraising decisions involving losses differently from those involving gains. To directly test for the evolutionary origin of this bias, we examined decision-making in humans' closest living relatives: bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). We presented the largest sample of non-humans to date (n = 40) with a simple task requiring minimal experience. Apes made choices between a 'framed' option that provided preferred food, and an alternative option that provided a constant amount of intermediately preferred food. In the gain condition, apes experienced a positive 'gain' event in which the framed option was initially presented as one piece of food but sometimes was augmented to two. In the loss condition, apes experienced a negative 'loss' event in which they initially saw two pieces but sometimes received only one. Both conditions provided equal pay-offs, but apes chose the framed option more often in the positive 'gain' frame. Moreover, male apes were more susceptible to framing than were females. These results suggest that some human economic biases are shared through common descent with other apes and highlight the importance of comparative work in understanding the origins of individual differences in human choice. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  11. The Human Semicircular Canals Orientation Is More Similar to the Bonobos than to the Chimpanzees

    Science.gov (United States)

    El Khoury, Marwan; Braga, José; Dumoncel, Jean; Nancy, Javotte; Esclassan, Remi; Vaysse, Frederic

    2014-01-01

    For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than they are to each other. Therefore, it becomes crucial to understand whether and how morphostructural differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we comparatively investigated intra and extra labyrinthine semicircular canals orientation using 260 computed tomography scans of extant humans (Homo sapiens), bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). Humans and bonobos proved more similarities between themselves than with chimpanzees. This finding did not fit with the well established chimpanzee – bonobo monophyly. One hypothesis was convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selective pressures that may be associated with postural adaptations. Another possibility was convergence following a “random walk” (Brownian motion) evolutionary model. A more parsimonious explanation was that the bonobo-human labyrinthine shared morphology more closely retained the ancestral condition with chimpanzees being subsequently derived. Finally, these results might be a consequence of genetic diversity and incomplete lineage sorting. The remarkable symmetry of the Semicircular Canals was the second major finding of this article with possible applications in taphonomy. It has the potential to investigate altered fossils, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology. PMID:24710502

  12. The human semicircular canals orientation is more similar to the bonobos than to the chimpanzees.

    Directory of Open Access Journals (Sweden)

    Marwan El Khoury

    Full Text Available For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than they are to each other. Therefore, it becomes crucial to understand whether and how morphostructural differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we comparatively investigated intra and extra labyrinthine semicircular canals orientation using 260 computed tomography scans of extant humans (Homo sapiens, bonobos (Pan paniscus and chimpanzees (Pan troglodytes. Humans and bonobos proved more similarities between themselves than with chimpanzees. This finding did not fit with the well established chimpanzee - bonobo monophyly. One hypothesis was convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selective pressures that may be associated with postural adaptations. Another possibility was convergence following a "random walk" (Brownian motion evolutionary model. A more parsimonious explanation was that the bonobo-human labyrinthine shared morphology more closely retained the ancestral condition with chimpanzees being subsequently derived. Finally, these results might be a consequence of genetic diversity and incomplete lineage sorting. The remarkable symmetry of the Semicircular Canals was the second major finding of this article with possible applications in taphonomy. It has the potential to investigate altered fossils, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology.

  13. Reflections of the social environment in chimpanzee memory: applying rational analysis beyond humans.

    Science.gov (United States)

    Stevens, Jeffrey R; Marewski, Julian N; Schooler, Lael J; Gilby, Ian C

    2016-08-01

    In cognitive science, the rational analysis framework allows modelling of how physical and social environments impose information-processing demands onto cognitive systems. In humans, for example, past social contact among individuals predicts their future contact with linear and power functions. These features of the human environment constrain the optimal way to remember information and probably shape how memory records are retained and retrieved. We offer a primer on how biologists can apply rational analysis to study animal behaviour. Using chimpanzees ( Pan troglodytes ) as a case study, we modelled 19 years of observational data on their social contact patterns. Much like humans, the frequency of past encounters in chimpanzees linearly predicted future encounters, and the recency of past encounters predicted future encounters with a power function. Consistent with the rational analyses carried out for human memory, these findings suggest that chimpanzee memory performance should reflect those environmental regularities. In re-analysing existing chimpanzee memory data, we found that chimpanzee memory patterns mirrored their social contact patterns. Our findings hint that human and chimpanzee memory systems may have evolved to solve similar information-processing problems. Overall, rational analysis offers novel theoretical and methodological avenues for the comparative study of cognition.

  14. Reflections of the social environment in chimpanzee memory: applying rational analysis beyond humans

    Science.gov (United States)

    Marewski, Julian N.; Schooler, Lael J.; Gilby, Ian C.

    2016-01-01

    In cognitive science, the rational analysis framework allows modelling of how physical and social environments impose information-processing demands onto cognitive systems. In humans, for example, past social contact among individuals predicts their future contact with linear and power functions. These features of the human environment constrain the optimal way to remember information and probably shape how memory records are retained and retrieved. We offer a primer on how biologists can apply rational analysis to study animal behaviour. Using chimpanzees (Pan troglodytes) as a case study, we modelled 19 years of observational data on their social contact patterns. Much like humans, the frequency of past encounters in chimpanzees linearly predicted future encounters, and the recency of past encounters predicted future encounters with a power function. Consistent with the rational analyses carried out for human memory, these findings suggest that chimpanzee memory performance should reflect those environmental regularities. In re-analysing existing chimpanzee memory data, we found that chimpanzee memory patterns mirrored their social contact patterns. Our findings hint that human and chimpanzee memory systems may have evolved to solve similar information-processing problems. Overall, rational analysis offers novel theoretical and methodological avenues for the comparative study of cognition. PMID:27853606

  15. Chimpanzee autarky.

    Directory of Open Access Journals (Sweden)

    Sarah F Brosnan

    2008-01-01

    Full Text Available Economists believe that barter is the ultimate cause of social wealth--and even much of our human culture--yet little is known about the evolution and development of such behavior. It is useful to examine the circumstances under which other species will or will not barter to more fully understand the phenomenon. Chimpanzees (Pan troglodytes are an interesting test case as they are an intelligent species, closely related to humans, and known to participate in reciprocal interactions and token economies with humans, yet they have not spontaneously developed costly barter.Although chimpanzees do engage in noncostly barter, in which otherwise value-less tokens are exchanged for food, this lack of risk is not typical of human barter. Thus, we systematically examined barter in chimpanzees to ascertain under what circumstances chimpanzees will engage in costly barter of commodities, that is, trading food items for other food items with a human experimenter. We found that chimpanzees do barter, relinquishing lower value items to obtain higher value items (and not the reverse. However, they do not trade in all beneficial situations, maintaining possession of less preferred items when the relative gains they stand to make are small.Two potential explanations for this puzzling behavior are that chimpanzees lack ownership norms, and thus have limited opportunity to benefit from the gains of trade, and that chimpanzees' risk of defection is sufficiently high that large gains must be imminent to justify the risk. Understanding the conditions that support barter in chimpanzees may increase understanding of situations in which humans, too, do not maximize their gains.

  16. Chimpanzee autarky.

    Science.gov (United States)

    Brosnan, Sarah F; Grady, Mark F; Lambeth, Susan P; Schapiro, Steven J; Beran, Michael J

    2008-01-30

    Economists believe that barter is the ultimate cause of social wealth--and even much of our human culture--yet little is known about the evolution and development of such behavior. It is useful to examine the circumstances under which other species will or will not barter to more fully understand the phenomenon. Chimpanzees (Pan troglodytes) are an interesting test case as they are an intelligent species, closely related to humans, and known to participate in reciprocal interactions and token economies with humans, yet they have not spontaneously developed costly barter. Although chimpanzees do engage in noncostly barter, in which otherwise value-less tokens are exchanged for food, this lack of risk is not typical of human barter. Thus, we systematically examined barter in chimpanzees to ascertain under what circumstances chimpanzees will engage in costly barter of commodities, that is, trading food items for other food items with a human experimenter. We found that chimpanzees do barter, relinquishing lower value items to obtain higher value items (and not the reverse). However, they do not trade in all beneficial situations, maintaining possession of less preferred items when the relative gains they stand to make are small. Two potential explanations for this puzzling behavior are that chimpanzees lack ownership norms, and thus have limited opportunity to benefit from the gains of trade, and that chimpanzees' risk of defection is sufficiently high that large gains must be imminent to justify the risk. Understanding the conditions that support barter in chimpanzees may increase understanding of situations in which humans, too, do not maximize their gains.

  17. Evolution of the NANOG pseudogene family in the human and chimpanzee genomes

    Directory of Open Access Journals (Sweden)

    Maughan Peter J

    2006-02-01

    Full Text Available Abstract Background The NANOG gene is expressed in mammalian embryonic stem cells where it maintains cellular pluripotency. An unusually large family of pseudogenes arose from it with one unprocessed and ten processed pseudogenes in the human genome. This article compares the NANOG gene and its pseudogenes in the human and chimpanzee genomes and derives an evolutionary history of this pseudogene family. Results The NANOG gene and all pseudogenes except NANOGP8 are present at their expected orthologous chromosomal positions in the chimpanzee genome when compared to the human genome, indicating that their origins predate the human-chimpanzee divergence. Analysis of flanking DNA sequences demonstrates that NANOGP8 is absent from the chimpanzee genome. Conclusion Based on the most parsimonious ordering of inferred source-gene mutations, the deduced evolutionary origins for the NANOG pseudogene family in the human and chimpanzee genomes, in order of most ancient to most recent, are NANOGP6, NANOGP5, NANOGP3, NANOGP10, NANOGP2, NANOGP9, NANOGP7, NANOGP1, and NANOGP4. All of these pseudogenes were fixed in the genome of the human-chimpanzee common ancestor. NANOGP8 is the most recent pseudogene and it originated exclusively in the human lineage after the human-chimpanzee divergence. NANOGP1 is apparently an unprocessed pseudogene. Comparison of its sequence to the functional NANOG gene's reading frame suggests that this apparent pseudogene remained functional after duplication and, therefore, was subject to selection-driven conservation of its reading frame, and that it may retain some functionality or that its loss of function may be evolutionarily recent.

  18. Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology

    Science.gov (United States)

    Wang, Xiaoxia; Chow, Renee; Deng, Liwen; Anderson, Dan; Weidner, Noel; Godwin, Andrew K; Bewtra, Chanda; Zlotnik, Albert; Bui, Jack; Varki, Ajit; Varki, Nissi

    2011-01-01

    Siglecs (Sialic acid-binding Immunoglobulin Superfamily Lectins) are cell surface signaling receptors of the I-type lectin group that recognize sialic acid-bearing glycans. CD33-related-Siglecs are a subset with expression primarily in cells of hematopoietic origin and functional relevance to immune reactions. Earlier we reported a human-specific gene conversion event that markedly changed the coding region for the extracellular domain of Siglec-11, associated with human-specific expression in microglia (Hayakawa T, Angata T, Lewis AL, Mikkelsen TS, Varki NM, Varki A. 2005. A human-specific gene in microglia. Science. 309:1693). Analyzing human gene microarrays to define new patterns of expression, we observed high levels of SIGLEC11 transcript in the ovary and adrenal cortex. Thus, we examined human and chimpanzee tissues using a well-characterized anti-Siglec-11 mouse monoclonal antibody. Although adrenal expression was variable and confined to infiltrating macrophages in capillaries, ovarian expression of Siglec-11 in both humans and chimpanzees was on fibroblasts, the first example of Siglec expression on mesenchyme-derived stromal cells. Cytokines from such ovarian stromal fibroblasts play important roles in follicle development and ovulation. Stable transfection of SIGLEC11 into a primary human ovarian stromal fibroblast cell line altered the secretion of growth-regulated oncogene α, interleukin (IL)-10, IL-7, transforming growth factor β1 and tumor necrosis factor-α, cytokines involved in ovarian physiology. Probing for Siglec-11 ligands revealed distinct and strong mast cell expression in human ovaries, contrasting to diffuse stromal ligands in chimpanzee ovaries. Interestingly, there was a trend of increased Siglec-11 expression in post-menopausal ovaries compared with pre-menopausal ones. Siglec-11 expression was also found on human ovarian stromal tumors and in polycystic ovarian syndrome, a human-specific disease. These results indicate potential

  19. Comparative Serum Challenges Show Divergent Patterns of Gene Expression and Open Chromatin in Human and Chimpanzee.

    Science.gov (United States)

    Pizzollo, Jason; Nielsen, William J; Shibata, Yoichiro; Safi, Alexias; Crawford, Gregory E; Wray, Gregory A; Babbitt, Courtney C

    2018-03-01

    Humans experience higher rates of age-associated diseases than our closest living evolutionary relatives, chimpanzees. Environmental factors can explain many of these increases in disease risk, but species-specific genetic changes can also play a role. Alleles that confer increased disease susceptibility later in life can persist in a population in the absence of selective pressure if those changes confer positive adaptation early in life. One age-associated disease that disproportionately affects humans compared with chimpanzees is epithelial cancer. Here, we explored genetic differences between humans and chimpanzees in a well-defined experimental assay that mimics gene expression changes that happen during cancer progression: A fibroblast serum challenge. We used this assay with fibroblasts isolated from humans and chimpanzees to explore species-specific differences in gene expression and chromatin state with RNA-Seq and DNase-Seq. Our data reveal that human fibroblasts increase expression of genes associated with wound healing and cancer pathways; in contrast, chimpanzee gene expression changes are not concentrated around particular functional categories. Chromatin accessibility dramatically increases in human fibroblasts, yet decreases in chimpanzee cells during the serum response. Many regions of opening and closing chromatin are in close proximity to genes encoding transcription factors or genes involved in wound healing processes, further supporting the link between changes in activity of regulatory elements and changes in gene expression. Together, these expression and open chromatin data show that humans and chimpanzees have dramatically different responses to the same physiological stressor, and how a core physiological process can evolve quickly over relatively short evolutionary time scales.

  20. Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available With a draft genome-sequence assembly for the chimpanzee available, it is now possible to perform genome-wide analyses to identify, at a submicroscopic level, structural rearrangements that have occurred between chimpanzees and humans. The goal of this study was to investigate chromosomal regions that are inverted between the chimpanzee and human genomes. Using the net alignments for the builds of the human and chimpanzee genome assemblies, we identified a total of 1,576 putative regions of inverted orientation, covering more than 154 mega-bases of DNA. The DNA segments are distributed throughout the genome and range from 23 base pairs to 62 mega-bases in length. For the 66 inversions more than 25 kilobases (kb in length, 75% were flanked on one or both sides by (often unrelated segmental duplications. Using PCR and fluorescence in situ hybridization we experimentally validated 23 of 27 (85% semi-randomly chosen regions; the largest novel inversion confirmed was 4.3 mega-bases at human Chromosome 7p14. Gorilla was used as an out-group to assign ancestral status to the variants. All experimentally validated inversion regions were then assayed against a panel of human samples and three of the 23 (13% regions were found to be polymorphic in the human genome. These polymorphic inversions include 730 kb (at 7p22, 13 kb (at 7q11, and 1 kb (at 16q24 fragments with a 5%, 30%, and 48% minor allele frequency, respectively. Our results suggest that inversions are an important source of variation in primate genome evolution. The finding of at least three novel inversion polymorphisms in humans indicates this type of structural variation may be a more common feature of our genome than previously realized.

  1. Characterization and potential functional significance of human-chimpanzee large INDEL variation

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    Polavarapu Nalini

    2011-10-01

    Full Text Available Abstract Background Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression. Results Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them. Conclusions The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution.

  2. An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes

    DEFF Research Database (Denmark)

    Jin, Xin; He, Mingze; Ferguson, Betsy

    2012-01-01

    -human primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab...

  3. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees

    NARCIS (Netherlands)

    Goudsmit, J.; Debouck, C.; Meloen, R. H.; Smit, L.; Bakker, M.; Asher, D. M.; Wolff, A. V.; Gibbs, C. J.; Gajdusek, D. C.

    1988-01-01

    Chimpanzees are susceptible to infection by divergent strains of human immunodeficiency virus type 1 (HIV-1), none of which cause clinical or immunological abnormalities. Chimpanzees were inoculated with one of four strains of HIV-1: human T-lymphotropic virus (HTLV) type IIIB, lymphadenopathy virus

  4. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

    International Nuclear Information System (INIS)

    Arthur, L.O.; Pyle, S.W.; Nara, P.L.

    1987-01-01

    The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4 + and T8 + cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4 + cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo

  5. A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Bustamente, Carlos; Clark, Andrew G.

    2005-01-01

    Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect...... such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved...

  6. Gimme Gimme Gimme. The recent signing behaviour of chimpanzees (Pan troglodytes) in interactions with longterm human companions

    NARCIS (Netherlands)

    Rivas, E.C.M.

    2003-01-01

    This dissertation starts with a critical analysis of the scientific projects with signing chimpanzees, which were set up to see if chimpanzees could learn a human language. These projects consist of the research by the Gardners, the Fouts and the Terrace group. After the results of these projects

  7. Cultural assemblages show nested structure in humans and chimpanzees but not orangutans.

    Science.gov (United States)

    Kamilar, Jason M; Atkinson, Quentin D

    2014-01-07

    The evolution of hominin culture is well-documented in the archeological and fossil record, but such a record is largely absent for nonhuman primates. An alternative approach to studying cultural evolution is to examine patterns of modern cultural variation. In this article we measure nestedness across human and great ape "cultural repertoires" to gain insight into the accumulation and maintenance of putative cultural diversity in these species. Cultural assemblages are nested if cultures with a small repertoire of traits tend to comprise a proper subset of those traits present in more complex cultures. This nesting will occur if some traits are sequentially gained or lost, which may be because of the differential dispersal or extinction of traits. Here we apply statistical tools from ecology to examine the degree of nestedness in four datasets documenting the presence or absence of specific cultural traits across indigenous human populations in North America and New Guinea. We then compare the human data to patterns observed for putative cultural traits in chimpanzee and orangutan populations. In both humans and chimpanzees, cultural diversity is highly nonrandom, showing significant nested structure for all of the datasets examined. We find no evidence for nestedness in the orangutan cultural data. These findings are consistent with a sequential "layering" of cultural diversity in humans and chimpanzees, but not orangutans. Such an interpretation implies that the traits required for sequential cultural evolution first appeared in the last common ancestor of chimpanzees and humans.

  8. Insights from Human/Mouse genome comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.

    2003-03-30

    Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

  9. Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic Poliovirus Excretors and Emergency Postexposure Prophylaxis▿‡

    Science.gov (United States)

    Chen, Zhaochun; Chumakov, Konstantin; Dragunsky, Eugenia; Kouiavskaia, Diana; Makiya, Michelle; Neverov, Alexander; Rezapkin, Gennady; Sebrell, Andrew; Purcell, Robert

    2011-01-01

    Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2, thereby covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 μg/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection. The MAbs described here could be tested in clinical trials to determine whether they might be useful for treatment of immunocompromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case. PMID:21345966

  10. Using the NCBI Genome Databases to Compare the Genes for Human & Chimpanzee Beta Hemoglobin

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The beta hemoglobin protein is identical in humans and chimpanzees. In this tutorial, students see that even though the proteins are identical, the genes that code for them are not. There are many more differences in the introns than in the exons, which indicates that coding regions of DNA are more highly conserved than non-coding regions.

  11. Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2008-12-01

    Full Text Available Abstract Background Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human. Result The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase. Conclusion Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.

  12. Virtual dissection and comparative connectivity of the superior longitudinal fasciculus in chimpanzees and humans

    Science.gov (United States)

    Hecht, Erin E.; Gutman, David A.; Bradley, Bruce A.; Preuss, Todd M.; Stout, Dietrich

    2015-01-01

    Many of the behavioral capacities that distinguish humans from other primates rely on fronto-parietal circuits. The superior longitudinal fasciculus (SLF) is the primary white matter tract connecting lateral frontal with lateral parietal regions; it is distinct from the arcuate fasciculus, which interconnects the frontal and temporal lobes. Here we report a direct, quantitative comparison of SLF connectivity using virtual in vivo dissection of the SLF in chimpanzees and humans. SLF I, the superior-most branch of the SLF, showed similar patterns of connectivity between humans and chimpanzees, and was proportionally volumetrically larger in chimpanzees. SLF II, the middle branch, and SLF III, the inferior-most branch, showed species differences in frontal connectivity. In humans, SLF II showed greater connectivity with dorsolateral prefrontal cortex, whereas in chimps SLF II showed greater connectivity with the inferior frontal gyrus. SLF III was right-lateralized and proportionally volumetrically larger in humans, and human SLF III showed relatively reduced connectivity with dorsal premotor cortex and greater extension into the anterior inferior frontal gyrus, especially in the right hemisphere. These results have implications for the evolution of fronto-parietal functions including spatial attention to observed actions, social learning, and tool use, and are in line with previous research suggesting a unique role for the right anterior inferior frontal gyrus in the evolution of human fronto-parietal network architecture. PMID:25534109

  13. Distractor Effect of Auditory Rhythms on Self-Paced Tapping in Chimpanzees and Humans

    Science.gov (United States)

    Hattori, Yuko; Tomonaga, Masaki; Matsuzawa, Tetsuro

    2015-01-01

    Humans tend to spontaneously align their movements in response to visual (e.g., swinging pendulum) and auditory rhythms (e.g., hearing music while walking). Particularly in the case of the response to auditory rhythms, neuroscientific research has indicated that motor resources are also recruited while perceiving an auditory rhythm (or regular pulse), suggesting a tight link between the auditory and motor systems in the human brain. However, the evolutionary origin of spontaneous responses to auditory rhythms is unclear. Here, we report that chimpanzees and humans show a similar distractor effect in perceiving isochronous rhythms during rhythmic movement. We used isochronous auditory rhythms as distractor stimuli during self-paced alternate tapping of two keys of an electronic keyboard by humans and chimpanzees. When the tempo was similar to their spontaneous motor tempo, tapping onset was influenced by intermittent entrainment to auditory rhythms. Although this effect itself is not an advanced rhythmic ability such as dancing or singing, our results suggest that, to some extent, the biological foundation for spontaneous responses to auditory rhythms was already deeply rooted in the common ancestor of chimpanzees and humans, 6 million years ago. This also suggests the possibility of a common attentional mechanism, as proposed by the dynamic attending theory, underlying the effect of perceiving external rhythms on motor movement. PMID:26132703

  14. Extensive changes in the expression of the opioid genes between humans and chimpanzees.

    Science.gov (United States)

    Cruz-Gordillo, Peter; Fedrigo, Olivier; Wray, Gregory A; Babbitt, Courtney C

    2010-01-01

    The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences (PENK, PNOC, and OPRL1), with two others marginally significant (OPRM1 and OPRD1). Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of OPRM1, POMC, and PDYN between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes. Copyright © 2010 S. Karger AG, Basel.

  15. Distractor Effect of Auditory Rhythms on Self-Paced Tapping in Chimpanzees and Humans.

    Directory of Open Access Journals (Sweden)

    Yuko Hattori

    Full Text Available Humans tend to spontaneously align their movements in response to visual (e.g., swinging pendulum and auditory rhythms (e.g., hearing music while walking. Particularly in the case of the response to auditory rhythms, neuroscientific research has indicated that motor resources are also recruited while perceiving an auditory rhythm (or regular pulse, suggesting a tight link between the auditory and motor systems in the human brain. However, the evolutionary origin of spontaneous responses to auditory rhythms is unclear. Here, we report that chimpanzees and humans show a similar distractor effect in perceiving isochronous rhythms during rhythmic movement. We used isochronous auditory rhythms as distractor stimuli during self-paced alternate tapping of two keys of an electronic keyboard by humans and chimpanzees. When the tempo was similar to their spontaneous motor tempo, tapping onset was influenced by intermittent entrainment to auditory rhythms. Although this effect itself is not an advanced rhythmic ability such as dancing or singing, our results suggest that, to some extent, the biological foundation for spontaneous responses to auditory rhythms was already deeply rooted in the common ancestor of chimpanzees and humans, 6 million years ago. This also suggests the possibility of a common attentional mechanism, as proposed by the dynamic attending theory, underlying the effect of perceiving external rhythms on motor movement.

  16. Distractor Effect of Auditory Rhythms on Self-Paced Tapping in Chimpanzees and Humans.

    Science.gov (United States)

    Hattori, Yuko; Tomonaga, Masaki; Matsuzawa, Tetsuro

    2015-01-01

    Humans tend to spontaneously align their movements in response to visual (e.g., swinging pendulum) and auditory rhythms (e.g., hearing music while walking). Particularly in the case of the response to auditory rhythms, neuroscientific research has indicated that motor resources are also recruited while perceiving an auditory rhythm (or regular pulse), suggesting a tight link between the auditory and motor systems in the human brain. However, the evolutionary origin of spontaneous responses to auditory rhythms is unclear. Here, we report that chimpanzees and humans show a similar distractor effect in perceiving isochronous rhythms during rhythmic movement. We used isochronous auditory rhythms as distractor stimuli during self-paced alternate tapping of two keys of an electronic keyboard by humans and chimpanzees. When the tempo was similar to their spontaneous motor tempo, tapping onset was influenced by intermittent entrainment to auditory rhythms. Although this effect itself is not an advanced rhythmic ability such as dancing or singing, our results suggest that, to some extent, the biological foundation for spontaneous responses to auditory rhythms was already deeply rooted in the common ancestor of chimpanzees and humans, 6 million years ago. This also suggests the possibility of a common attentional mechanism, as proposed by the dynamic attending theory, underlying the effect of perceiving external rhythms on motor movement.

  17. In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized antibody in chimpanzees

    International Nuclear Information System (INIS)

    Hong, Hyo Jeong; Ryu, Chun Jeih; Hur, Hyangsuk; Kim, Seho; Oh, Han Kyu; Oh, Mee Sook; Park, Song Yong

    2004-01-01

    Previously, we generated a murine monoclonal antibody (mAb), KR127, that recognizes amino acids (aa) 37-45 of the preS1 of hepatitis B virus (HBV). In this study, we have constructed a humanized version of KR127 and evaluated its HBV-neutralizing activity in chimpanzees. A study chimpanzee was given a single intravenous dose of the humanized antibody, followed by intravenous challenge with adr subtype of wild type HBV, while a control chimpanzee was only challenged with the virus. The result showed that the study chimpanzee did not develop HBV infection during 1 year, while the control chimpanzee was infected, indicating that the humanized antibody exhibited in vivo virus-neutralizing activity and thus protected the chimpanzee from HBV infection. In addition, the humanized antibody bound to the preS1 of all subtypes of HBV. We first demonstrate that an anti-preS1 mAb can neutralize HBV infection in vivo. This humanized antibody will be useful for the immunoprophylaxis of HBV infection

  18. Neuromandibular integration in humans and chimpanzees: Implications for dental and mandibular reduction in Homo.

    Science.gov (United States)

    Veneziano, Alessio; Meloro, Carlo; Irish, Joel D; Stringer, Chris; Profico, Antonio; De Groote, Isabelle

    2018-05-08

    Although the evolution of the hominin masticatory apparatus has been linked to diet and food processing, the physical connection between neurocranium and lower jaw suggests a role of encephalization in the trend of dental and mandibular reduction. Here, the hypothesis that tooth size and mandibular robusticity are influenced by morphological changes in the neurocranium was tested. Three-dimensional landmarks, alveolar lengths, and mandibular robusticity data were recorded on a sample of chimpanzee and human skulls. The morphological integration between the neurocranium and the lower jaw was analyzed by means of Singular Warps Analysis. Redundancy Analysis was performed to understand if the pattern of neuromandibular integration affects tooth size and mandibular robusticity. There is significant morphological covariation between neurocranium and lower jaw in both chimpanzees and humans. In humans, changes in the temporal fossa seem to produce alterations of the relative orientation of jaw parts, while the influence of similar neurocranial changes in chimpanzees are more localized. In both species, postcanine alveolar lengths and mandibular robusticity are associated with shape changes of the temporal fossa. The results of this study support the hypothesis that the neurocranium is able to affect the evolution and development of the lower jaw, although most likely through functional integration of mandible, teeth, and muscles within the masticatory apparatus. This study highlights the relative influence of structural constraints and adaptive factors in the evolution of the human skull. © 2018 Wiley Periodicals, Inc.

  19. Form and function of the human and chimpanzee forefoot: implications for early hominin bipedalism

    Science.gov (United States)

    Fernández, Peter J.; Holowka, Nicholas B.; Demes, Brigitte; Jungers, William L.

    2016-01-01

    During bipedal walking, modern humans dorsiflex their forefoot at the metatarsophalangeal joints (MTPJs) prior to push off, which tightens the plantar soft tissues to convert the foot into a stiff propulsive lever. Particular features of metatarsal head morphology such as “dorsal doming” are thought to facilitate this stiffening mechanism. In contrast, chimpanzees are believed to possess MTPJ morphology that precludes high dorsiflexion excursions during terrestrial locomotion. The morphological affinity of the metatarsal heads has been used to reconstruct locomotor behavior in fossil hominins, but few studies have provided detailed empirical data to validate the assumed link between morphology and function at the MTPJs. Using three-dimensional kinematic and morphometric analyses, we show that humans push off with greater peak dorsiflexion angles at all MTPJs than do chimpanzees during bipedal and quadrupedal walking, with the greatest disparity occurring at MTPJ 1. Among MTPJs 2–5, both species exhibit decreasing peak angles from medial to lateral. This kinematic pattern is mirrored in the morphometric analyses of metatarsal head shape. Analyses of Australopithecus afarensis metatarsals reveal morphology intermediate between humans and chimpanzees, suggesting that this species used different bipedal push-off kinematics than modern humans, perhaps resulting in a less efficient form of bipedalism. PMID:27464580

  20. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts

    KAUST Repository

    Otto, Thomas D.

    2014-09-09

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host–parasite interface may have mediated host switching.

  1. Visuoauditory mappings between high luminance and high pitch are shared by chimpanzees (Pan troglodytes) and humans

    Science.gov (United States)

    Ludwig, Vera U.; Adachi, Ikuma; Matsuzawa, Tetsuro

    2011-01-01

    Humans share implicit preferences for certain cross-sensory combinations; for example, they consistently associate higher-pitched sounds with lighter colors, smaller size, and spikier shapes. In the condition of synesthesia, people may experience such cross-modal correspondences to a perceptual degree (e.g., literally seeing sounds). So far, no study has addressed the question whether nonhuman animals share cross-modal correspondences as well. To establish the evolutionary origins of cross-modal mappings, we tested whether chimpanzees (Pan troglodytes) also associate higher pitch with higher luminance. Thirty-three humans and six chimpanzees were required to classify black and white squares according to their color while hearing irrelevant background sounds that were either high-pitched or low-pitched. Both species performed better when the background sound was congruent (high-pitched for white, low-pitched for black) than when it was incongruent (low-pitched for white, high-pitched for black). An inherent tendency to pair high pitch with high luminance hence evolved before the human lineage split from that of chimpanzees. Rather than being a culturally learned or a linguistic phenomenon, this mapping constitutes a basic feature of the primate sensory system. PMID:22143791

  2. THE SIGNIFICANCE OF LESIONS IN PERIPHERAL GANGLIA IN CHIMPANZEE AND IN HUMAN POLIOMYELITIS

    Science.gov (United States)

    Bodian, David; Howe, Howard A.

    1947-01-01

    1. The peripheral ganglia of eighteen inoculated chimpanzees and thirteen uninoculated controls, and of eighteen fatal human poliomyelitis cases, were studied for histopathological evidence of the route of transmission of virus from the alimentary tract to the CNS. 2. Lesions thought to be characteristic of poliomyelitis in inoculated chimpanzees could not be sharply differentiated from lesions of unknown origin in uninoculated control animals. Moreover, although the inoculated animals as a group, in comparison with the control animals, had a greater number of infiltrative lesions in sympathetic as well as in sensory ganglia, it was not possible to make satisfactory correlations between the distribution of these lesions and the routes of inoculation. 3. In sharp contrast with chimpanzees, the celiac and stellate ganglia of the human poliomyelitis cases were free of any but insignificant infiltrative lesions. Lesions in human trigeminal and spinal sensory ganglia included neuronal damage as well as focal and perivascular inflitrative lesions, as is well known. In most ganglia, as in monkey and chimpanzee sensory ganglia, these were correlated in intensify with the degree of severity of lesions in the region of the CNS receiving their axons. This suggested that lesions in sensory ganglia probably resulted from spread of virus centrifugally from the CNS, in accord with considerable experimental evidence. 4. Two principal difficulties in the interpretation of histopathological findings in peripheral ganglia were revealed by this study. The first is that the specificity of lesions in sympathetic ganglia has not been established beyond doubt as being due to poliomyelitis. The second is that the presence of characteristic lesions in sensory ganglia does not, and cannot, reveal whether the virus reached the ganglia from the periphery or from the central nervous system, except in very early preparalytic stages or in exceptional cases of early arrest of virus spread and of

  3. The genetic signature of sex-biased migration in patrilocal chimpanzees and humans.

    Directory of Open Access Journals (Sweden)

    Kevin E Langergraber

    Full Text Available A large body of theoretical work suggests that analyses of variation at the maternally inherited mitochondrial (mtDNA and the paternally inherited non-recombining portion of the Y chromosome (NRY are a potentially powerful way to reveal the differing migratory histories of men and women across human societies. However, the few empirical studies comparing mtDNA and NRY variation and known patterns of sex-biased migration have produced conflicting results. Here we review some methodological reasons for these inconsistencies, and take them into account to provide an unbiased characterization of mtDNA and NRY variation in chimpanzees, one of the few mammalian taxa where males routinely remain in and females typically disperse from their natal groups. We show that patterns of mtDNA and NRY variation are more strongly contrasting in patrilocal chimpanzees compared with patrilocal human societies. The chimpanzee data we present here thus provide a valuable comparative benchmark of the patterns of mtDNA and NRY variation to be expected in a society with extremely female-biased dispersal.

  4. Brief Communication: Quantitative- and molecular-genetic differentiation in humans and chimpanzees: implications for the evolutionary processes underlying cranial diversification.

    Science.gov (United States)

    Weaver, Timothy D

    2014-08-01

    Estimates of the amount of genetic differentiation in humans among major geographic regions (e.g., Eastern Asia vs. Europe) from quantitative-genetic analyses of cranial measurements closely match those from classical- and molecular-genetic markers. Typically, among-region differences account for ∼10% of the total variation. This correspondence is generally interpreted as evidence for the importance of neutral evolutionary processes (e.g., genetic drift) in generating among-region differences in human cranial form, but it was initially surprising because human cranial diversity was frequently assumed to show a strong signature of natural selection. Is the human degree of similarity of cranial and DNA-sequence estimates of among-region genetic differentiation unusual? How do comparisons with other taxa illuminate the evolutionary processes underlying cranial diversification? Chimpanzees provide a useful starting point for placing the human results in a broader comparative context, because common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the extant species most closely related to humans. To address these questions, I used 27 cranial measurements collected on a sample of 861 humans and 263 chimpanzees to estimate the amount of genetic differentiation between pairs of groups (between regions for humans and between species or subspecies for chimpanzees). Consistent with previous results, the human cranial estimates are quite similar to published DNA-sequence estimates. In contrast, the chimpanzee cranial estimates are much smaller than published DNA-sequence estimates. It appears that cranial differentiation has been limited in chimpanzees relative to humans. © 2014 Wiley Periodicals, Inc.

  5. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts

    KAUST Repository

    Otto, Thomas D.; Rayner, Julian C.; Bö hme, Ulrike; Pain, Arnab; Spottiswoode, Natasha; Sanders, Mandy; Quail, Michael; Ollomo, Benjamin; Renaud, Franç ois; Thomas, Alan W.; Prugnolle, Franck; Conway, David J.; Newbold, Chris; Berriman, Matthew

    2014-01-01

    related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete

  6. Evolutionary Divergence of Gene and Protein Expression in the Brains of Humans and Chimpanzees.

    Science.gov (United States)

    Bauernfeind, Amy L; Soderblom, Erik J; Turner, Meredith E; Moseley, M Arthur; Ely, John J; Hof, Patrick R; Sherwood, Chet C; Wray, Gregory A; Babbitt, Courtney C

    2015-07-10

    Although transcriptomic profiling has become the standard approach for exploring molecular differences in the primate brain, very little is known about how the expression levels of gene transcripts relate to downstream protein abundance. Moreover, it is unknown whether the relationship changes depending on the brain region or species under investigation. We performed high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses on two regions of the human and chimpanzee brain: The anterior cingulate cortex and caudate nucleus. In both brain regions, we found a lower correlation between mRNA and protein expression levels in humans and chimpanzees than has been reported for other tissues and cell types, suggesting that the brain may engage extensive tissue-specific regulation affecting protein abundance. In both species, only a few categories of biological function exhibited strong correlations between mRNA and protein expression levels. These categories included oxidative metabolism and protein synthesis and modification, indicating that the expression levels of mRNA transcripts supporting these biological functions are more predictive of protein expression compared with other functional categories. More generally, however, the two measures of molecular expression provided strikingly divergent perspectives into differential expression between human and chimpanzee brains: mRNA comparisons revealed significant differences in neuronal communication, ion transport, and regulatory processes, whereas protein comparisons indicated differences in perception and cognition, metabolic processes, and organization of the cytoskeleton. Our results highlight the importance of examining protein expression in evolutionary analyses and call for a more thorough understanding of tissue-specific protein expression levels. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular

  7. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  8. Species association of hepatitis B virus (HBV in non-human apes; evidence for recombination between gorilla and chimpanzee variants.

    Directory of Open Access Journals (Sweden)

    Sinéad Lyons

    Full Text Available Hepatitis B virus (HBV infections are widely distributed in humans, infecting approximately one third of the world's population. HBV variants have also been detected and genetically characterised from Old World apes; Gorilla gorilla (gorilla, Pan troglodytes (chimpanzee, Pongo pygmaeus (orang-utan, Nomascus nastusus and Hylobates pileatus (gibbons and from the New World monkey, Lagothrix lagotricha (woolly monkey. To investigate species-specificity and potential for cross species transmission of HBV between sympatric species of apes (such as gorillas and chimpanzees in Central Africa or between humans and chimpanzees or gorillas, variants of HBV infecting captive wild-born non-human primates were genetically characterised. 9 of 62 chimpanzees (11.3% and two from 11 gorillas (18% were HBV-infected (15% combined frequency, while other Old world monkey species were negative. Complete genome sequences were obtained from six of the infected chimpanzee and both gorillas; those from P. t .ellioti grouped with previously characterised variants from this subspecies. However, variants recovered from P. t. troglodytes HBV variants also grouped within this clade, indicative of transmission between sub-species, forming a paraphyletic clade. The two gorilla viruses were phylogenetically distinct from chimpanzee and human variants although one showed evidence for a recombination event with a P.t.e.-derived HBV variant in the partial X and core gene region. Both of these observations provide evidence for circulation of HBV between different species and sub-species of non-human primates, a conclusion that differs from the hypothesis if of strict host specificity of HBV genotypes.

  9. Campylobacter troglodytis sp. nov., Isolated from Feces of Human-Habituated Wild Chimpanzees (Pan troglodytes schweinfurthii) in Tanzania ▿

    Science.gov (United States)

    Kaur, Taranjit; Singh, Jatinder; Huffman, Michael A.; Petrželková, Klára J.; Taylor, Nancy S.; Xu, Shilu; Dewhirst, Floyd E.; Paster, Bruce J.; Debruyne, Lies; Vandamme, Peter; Fox, James G.

    2011-01-01

    The transmission of simian immunodeficiency and Ebola viruses to humans in recent years has heightened awareness of the public health significance of zoonotic diseases of primate origin, particularly from chimpanzees. In this study, we analyzed 71 fecal samples collected from 2 different wild chimpanzee (Pan troglodytes) populations with different histories in relation to their proximity to humans. Campylobacter spp. were detected by culture in 19/56 (34%) group 1 (human habituated for research and tourism purposes at Mahale Mountains National Park) and 0/15 (0%) group 2 (not human habituated but propagated from an introduced population released from captivity over 30 years ago at Rubondo Island National Park) chimpanzees, respectively. Using 16S rRNA gene sequencing, all isolates were virtually identical (at most a single base difference), and the chimpanzee isolates were most closely related to Campylobacter helveticus and Campylobacter upsaliensis (94.7% and 95.9% similarity, respectively). Whole-cell protein profiling, amplified fragment length polymorphism analysis of genomic DNA, hsp60 sequence analysis, and determination of the mol% G+C content revealed two subgroups among the chimpanzee isolates. DNA-DNA hybridization experiments confirmed that both subgroups represented distinct genomic species. In the absence of differential biochemical characteristics and morphology and identical 16S rRNA gene sequences, we propose to classify all isolates into a single novel nomenspecies, Campylobacter troglodytis, with strain MIT 05-9149 as the type strain; strain MIT 05-9157 is suggested as the reference strain for the second C. troglodytis genomovar. Further studies are required to determine whether the organism is pathogenic to chimpanzees and whether this novel Campylobacter colonizes humans and causes enteric disease. PMID:21278267

  10. Campylobacter troglodytis sp. nov., isolated from feces of human-habituated wild chimpanzees (Pan troglodytes schweinfurthii) in Tanzania.

    Science.gov (United States)

    Kaur, Taranjit; Singh, Jatinder; Huffman, Michael A; Petrzelková, Klára J; Taylor, Nancy S; Xu, Shilu; Dewhirst, Floyd E; Paster, Bruce J; Debruyne, Lies; Vandamme, Peter; Fox, James G

    2011-04-01

    The transmission of simian immunodeficiency and Ebola viruses to humans in recent years has heightened awareness of the public health significance of zoonotic diseases of primate origin, particularly from chimpanzees. In this study, we analyzed 71 fecal samples collected from 2 different wild chimpanzee (Pan troglodytes) populations with different histories in relation to their proximity to humans. Campylobacter spp. were detected by culture in 19/56 (34%) group 1 (human habituated for research and tourism purposes at Mahale Mountains National Park) and 0/15 (0%) group 2 (not human habituated but propagated from an introduced population released from captivity over 30 years ago at Rubondo Island National Park) chimpanzees, respectively. Using 16S rRNA gene sequencing, all isolates were virtually identical (at most a single base difference), and the chimpanzee isolates were most closely related to Campylobacter helveticus and Campylobacter upsaliensis (94.7% and 95.9% similarity, respectively). Whole-cell protein profiling, amplified fragment length polymorphism analysis of genomic DNA, hsp60 sequence analysis, and determination of the mol% G+C content revealed two subgroups among the chimpanzee isolates. DNA-DNA hybridization experiments confirmed that both subgroups represented distinct genomic species. In the absence of differential biochemical characteristics and morphology and identical 16S rRNA gene sequences, we propose to classify all isolates into a single novel nomenspecies, Campylobacter troglodytis, with strain MIT 05-9149 as the type strain; strain MIT 05-9157 is suggested as the reference strain for the second C. troglodytis genomovar. Further studies are required to determine whether the organism is pathogenic to chimpanzees and whether this novel Campylobacter colonizes humans and causes enteric disease.

  11. The Conditions Favoring Between-Community Raiding in Chimpanzees, Bonobos, and Human Foragers.

    Science.gov (United States)

    Pandit, Sagar A; Pradhan, Gauri R; Balashov, Hennadii; Van Schaik, Carel P

    2016-06-01

    Chimpanzees, bonobos, and human foragers share a fission-fusion social system and a mating system of joint male resource defense polygyny. Within-community skew in male strength varies among and within species. In this study, we extend a mathematical model of within-group male coalition formation among primates to derive the conditions for between-community conflicts in the form of raids. We show that the main factor affecting the presence of successful raiding is the likelihood of major discrepancies in party strength, which are set by party size distributions (and thus community size) and the skew in strength. This study confirms the functional similarities between the raiding of chimpanzees and human foragers, and it supports the "imbalance of power" hypothesis for raiding. However, it also proposes two amendments to this model. First, the absence of raiding in bonobos may be attributable more to potential female involvement in defense against raids, which increases the size of defensive coalitions. Second, the model attributes some of the raiding in humans to major contrasts in instantaneous fighting ability created by surprise raids on unarmed victims; it also draws attention to the distinction between minor raids and major raids that involve multiple bands of the same community.

  12. A scan for positively selected genes in the genomes of humans and chimpanzees.

    Directory of Open Access Journals (Sweden)

    Rasmus Nielsen

    2005-06-01

    Full Text Available Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

  13. Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages.

    Science.gov (United States)

    Han, Kyudong; Sen, Shurjo K; Wang, Jianxin; Callinan, Pauline A; Lee, Jungnam; Cordaux, Richard; Liang, Ping; Batzer, Mark A

    2005-01-01

    Long INterspersed Elements (LINE-1s or L1s) are abundant non-LTR retrotransposons in mammalian genomes that are capable of insertional mutagenesis. They have been associated with target site deletions upon insertion in cell culture studies of retrotransposition. Here, we report 50 deletion events in the human and chimpanzee genomes directly linked to the insertion of L1 elements, resulting in the loss of approximately 18 kb of sequence from the human genome and approximately 15 kb from the chimpanzee genome. Our data suggest that during the primate radiation, L1 insertions may have deleted up to 7.5 Mb of target genomic sequences. While the results of our in vivo analysis differ from those of previous cell culture assays of L1 insertion-mediated deletions in terms of the size and rate of sequence deletion, evolutionary factors can reconcile the differences. We report a pattern of genomic deletion sizes similar to those created during the retrotransposition of Alu elements. Our study provides support for the existence of different mechanisms for small and large L1-mediated deletions, and we present a model for the correlation of L1 element size and the corresponding deletion size. In addition, we show that internal rearrangements can modify L1 structure during retrotransposition events associated with large deletions.

  14. Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence

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    Kim Dong Seon

    2012-11-01

    Full Text Available Abstract Background Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence. Results We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of SMOX gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways. Conclusions Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution.

  15. An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes.

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    Xin Jin

    Full Text Available Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger-based resequencing validated 85.4% of 41 randomly selected SNPs. Among the short indels identified, a majority (54.6%-77.3% of the variants resulted in a change of 3 base pairs, consistent with expectations for a selection against frame shift mutations. Taken together, these findings indicate that use of a human design exon-capture array can provide efficient enrichment of non-human primate gene regions. Accordingly, use of the human exon-capture methods provides an attractive, cost-effective approach for the comparative analysis of non-human primate genomes, including gene-based DNA variant discovery.

  16. Characteristics of primary infection of a European human immunodeficiency virus type 1 clade B isolate in chimpanzees

    NARCIS (Netherlands)

    Bogers, W. M.; Koornstra, W. H.; Dubbes, R. H.; ten Haaft, P. J.; Verstrepen, B. E.; Jhagjhoorsingh, S. S.; Haaksma, A. G.; Niphuis, H.; Laman, J. D.; Norley, S.; Schuitemaker, H.; Goudsmit, J.; Hunsmann, G.; Heeney, J. L.; Wigzell, H.

    1998-01-01

    The aim of the study was to select, from a panel of candidate European human immunodeficiency virus type 1 (HIV-1) clade B primary virus isolates, one isolate based on replication properties in chimpanzee peripheral blood mononuclear cells (PBMC). Secondly, to evaluate the in vivo kinetics of

  17. Evaluating the relationship between spermatogenic silencing of the X chromosome and evolution of the Y chromosome in chimpanzee and human

    NARCIS (Netherlands)

    E. Mulugeta (Eskeatnaf); W.M. Baarends (Willy); J.H. Gribnau (Joost); J.A. Grootegoed (Anton)

    2010-01-01

    textabstractChimpanzees and humans are genetically very similar, with the striking exception of their Y chromosomes, which have diverged tremendously. The male-specific region (MSY), representing the greater part of the Y chromosome, is inherited from father to son in a clonal fashion, with natural

  18. Can Chimpanzee Infants ("Pan Troglodytes") Form Categorical Representations in the Same Manner as Human Infants ("Homo Sapiens")?

    Science.gov (United States)

    Murai, Chizuko; Kosugi, Daisuke; Tomonaga, Masaki; Tanaka, Masayuki; Matsuzawa, Tetsuro; Itakura, Shoji

    2005-01-01

    We directly compared chimpanzee infants and human infants for categorical representations of three global-like categories (mammals, furniture and vehicles), using the familiarization-novelty preference technique. Neither species received any training during the experiments. We used the time that participants spent looking at the stimulus object…

  19. An Exon-Based Comparative Variant Analysis Pipeline to Study the Scale and Role of Frameshift and Nonsense Mutation in the Human-Chimpanzee Divergence

    Directory of Open Access Journals (Sweden)

    GongXin Yu

    2009-01-01

    important biological processes such as T cell lineage development, the pathogenesis of inflammatory diseases, and antigen induced cell death. A “less-is-more” model was previously established to illustrate the role of the gene inactivation and disruptions during human evolution. Here this analysis suggested a different model where the chimpanzee-specific exon-disrupting mutations may act as additional evolutionary force that drove the human-chimpanzee divergence. Finally, the analysis revealed a number of sequencing errors in the chimpanzee and human genome sequences and further illustrated that they could be corrected without resequencing.

  20. Development and evaluation of new mask protocols for gene expression profiling in humans and chimpanzees

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    Siegmund Kimberly D

    2009-03-01

    Full Text Available Abstract Background Cross-species gene expression analyses using oligonucleotide microarrays designed to evaluate a single species can provide spurious results due to mismatches between the interrogated transcriptome and arrayed probes. Based on the most recent human and chimpanzee genome assemblies, we developed updated and accessible probe masking methods that allow human Affymetrix oligonucleotide microarrays to be used for robust genome-wide expression analyses in both species. In this process, only data from oligonucleotide probes predicted to have robust hybridization sensitivity and specificity for both transcriptomes are retained for analysis. Results To characterize the utility of this resource, we applied our mask protocols to existing expression data from brains, livers, hearts, testes, and kidneys derived from both species and determined the effects probe numbers have on expression scores of specific transcripts. In all five tissues, probe sets with decreasing numbers of probes showed non-linear trends towards increased variation in expression scores. The relationships between expression variation and probe number in brain data closely matched those observed in simulated expression data sets subjected to random probe masking. However, there is evidence that additional factors affect the observed relationships between gene expression scores and probe number in tissues such as liver and kidney. In parallel, we observed that decreasing the number of probes within probe sets lead to linear increases in both gained and lost inferences of differential cross-species expression in all five tissues, which will affect the interpretation of expression data subject to masking. Conclusion We introduce a readily implemented and updated resource for human and chimpanzee transcriptome analysis through a commonly used microarray platform. Based on empirical observations derived from the analysis of five distinct data sets, we provide novel guidelines

  1. Autonomy in chimpanzees.

    Science.gov (United States)

    Beauchamp, Tom L; Wobber, Victoria

    2014-04-01

    Literature on the mental capacities and cognitive mechanisms of the great apes has been silent about whether they can act autonomously. This paper provides a philosophical theory of autonomy supported by psychological studies of the cognitive mechanisms that underlie chimpanzee behavior to argue that chimpanzees can act autonomously even though their psychological mechanisms differ from those of humans. Chimpanzees satisfy the two basic conditions of autonomy: (1) liberty (the absence of controlling influences) and (2) agency (self-initiated intentional action), each of which is specified here in terms of conditions of understanding, intention, and self-control. In this account, chimpanzees make knowledge-based choices reflecting a richly information-based and socially sophisticated understanding of the world. Finally, two major theories of autonomy (Kantian theory and two-level theory) are rejected as too narrow to adequately address these issues, necessitating the modifications made in the present approach.

  2. Chimpanzees share forbidden fruit.

    Directory of Open Access Journals (Sweden)

    Kimberley J Hockings

    2007-09-01

    Full Text Available The sharing of wild plant foods is infrequent in chimpanzees, but in chimpanzee communities that engage in hunting, meat is frequently used as a 'social tool' for nurturing alliances and social bonds. Here we report the only recorded example of regular sharing of plant foods by unrelated, non-provisioned wild chimpanzees, and the contexts in which these sharing behaviours occur. From direct observations, adult chimpanzees at Bossou (Republic of Guinea, West Africa very rarely transferred wild plant foods. In contrast, they shared cultivated plant foods much more frequently (58 out of 59 food sharing events. Sharing primarily consists of adult males allowing reproductively cycling females to take food that they possess. We propose that hypotheses focussing on 'food-for-sex and -grooming' and 'showing-off' strategies plausibly account for observed sharing behaviours. A changing human-dominated landscape presents chimpanzees with fresh challenges, and our observations suggest that crop-raiding provides adult male chimpanzees at Bossou with highly desirable food commodities that may be traded for other currencies.

  3. Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq.

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    Augix Guohua Xu

    Full Text Available Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts located outside of the known genes' boundaries is limited. Here, we use high-throughput transcriptome sequencing (RNA-Seq to characterize the total non-ribosomal transcriptome of human, chimpanzee, and rhesus macaque brain. In all species, only 20-28% of non-ribosomal transcripts correspond to annotated exons and 20-23% to introns. By contrast, transcripts originating within intronic and intergenic repetitive sequences constitute 40-48% of the total brain transcriptome. Notably, some repeat families show elevated transcription. In non-repetitive intergenic regions, we identify and characterize 1,093 distinct regions highly expressed in the human brain. These regions are conserved at the RNA expression level across primates studied and at the DNA sequence level across mammals. A large proportion of these transcripts (20% represents 3'UTR extensions of known genes and may play roles in alternative microRNA-directed regulation. Finally, we show that while transcriptome divergence between species increases with evolutionary time, intergenic transcripts show more expression differences among species and exons show less. Our results show that many yet uncharacterized evolutionary conserved transcripts exist in the human brain. Some of these transcripts may play roles in transcriptional regulation and contribute to evolution of human-specific phenotypic traits.

  4. Cross-comparison of the genome sequences from human, chimpanzee, Neanderthal and a Denisovan hominin identifies novel potentially compensated mutations

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    Zhang Guojie

    2011-07-01

    Full Text Available Abstract The recent publication of the draft genome sequences of the Neanderthal and a ~50,000-year-old archaic hominin from Denisova Cave in southern Siberia has ushered in a new age in molecular archaeology. We previously cross-compared the human, chimpanzee and Neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (Human Gene Mutation Database and succeeded in identifying genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species. Here, in an attempt to identify further 'potentially compensated mutations' (PCMs of interest, we have compared our dataset of disease-causing/disease-associated mutations with their corresponding nucleotide positions in the Denisovan hominin, Neanderthal and chimpanzee genomes. Of the 15 human putatively disease-causing mutations that were found to be compensated in chimpanzee, Denisovan or Neanderthal, only a solitary F5 variant (Val1736Met was specific to the Denisovan. In humans, this missense mutation is associated with activated protein C resistance and an increased risk of thromboembolism and recurrent miscarriage. It is unclear at this juncture whether this variant was indeed a PCM in the Denisovan or whether it could instead have been associated with disease in this ancient hominin.

  5. A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues.

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    Athma A Pai

    2011-02-01

    Full Text Available The modification of DNA by methylation is an important epigenetic mechanism that affects the spatial and temporal regulation of gene expression. Methylation patterns have been described in many contexts within and across a range of species. However, the extent to which changes in methylation might underlie inter-species differences in gene regulation, in particular between humans and other primates, has not yet been studied. To this end, we studied DNA methylation patterns in livers, hearts, and kidneys from multiple humans and chimpanzees, using tissue samples for which genome-wide gene expression data were also available. Using the multi-species gene expression and methylation data for 7,723 genes, we were able to study the role of promoter DNA methylation in the evolution of gene regulation across tissues and species. We found that inter-tissue methylation patterns are often conserved between humans and chimpanzees. However, we also found a large number of gene expression differences between species that might be explained, at least in part, by corresponding differences in methylation levels. In particular, we estimate that, in the tissues we studied, inter-species differences in promoter methylation might underlie as much as 12%-18% of differences in gene expression levels between humans and chimpanzees.

  6. Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees (Pan troglodytes), Bonobos (Pan paniscus), and Humans (Homo sapiens)

    OpenAIRE

    Potau, J. M.; Arias-Martorell, J.; Bello-Hellegouarch, G.; Casado, A.; Pastor, J. F.; de Paz, F.; Diogo, R.

    2018-01-01

    We have analyzed anatomic variations in the pectoralis major and pectoralis minor muscles of common chimpanzees (Pan\\ud troglodytes) and bonobos(Pan paniscus) and compared them to anatomic variations in these muscles in humans(Homo sapiens). We\\ud have macroscopically dissected these muscles in six adult Pan troglodytes, five Pan paniscus of ages ranging from fetus to adult, and\\ud five adult Homo sapiens. Although Pan troglodytes are thought to lack a separate pectoralis abdominis muscle, we...

  7. Convergence and divergence of tumor-suppressor and proto-oncogenes in chimpanzee from human chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Verma, R.S.; Ramesh, K.H. [Long Island College Hospital, Brooklyn, NY (United States)

    1994-09-01

    Due to the emergence of molecular technology, the phylogenetic evolution of the human genome via apes has become a saltatory even. In the present investigation, cosmid probes for P53, Charcot-Marie-Tooth [CMTIA], HER-2/NEU and myeloperoxidase [MPO] were used. Probes mapping to these genetic loci are well-defined on human chromosome 17 [HSA 17]. We localized these genes on chimpanzee [Pan troglodyte] chromosomes by FISH technique employing two different cell lines. Our results indicate that chimpanzee chromosome 19 [PTR 19] differs from HSA 17 by a pericentric inversion. The P53 gene assigned to HSA 17p13.1 is localized on PTR 19p15 and the MPO sequence of HSA 17q21.3-23 hybridized to PTR 19q23. Perplexing enough, HER-2/NEU assigned to HSA 17q11.2 localized to PTR 19p12. Obviously, there is convergence of P53 and MPO regions and distinctive divergence of HER-2/NEU and CMT1A regions of human and chimpanzee. This investigation has demonstrated the pronounced genetic shuffling which occurred during the origin of HSA 17. Molecular markers should serve as evolutionary punctuations in defining the precise sequence of genetic events that led to the evolution of other chromosomes whose genomic synteny, although similar, have surprisingly evolved through different mechanisms.

  8. Can chimpanzee infants (Pan troglodytes) form categorical representations in the same manner as human infants (Homo sapiens)?

    Science.gov (United States)

    Murai, Chizuko; Kosugi, Daisuke; Tomonaga, Masaki; Tanaka, Masayuki; Matsuzawa, Tetsuro; Itakura, Shoji

    2005-05-01

    We directly compared chimpanzee infants and human infants for categorical representations of three global-like categories (mammals, furniture and vehicles), using the familiarization-novelty preference technique. Neither species received any training during the experiments. We used the time that participants spent looking at the stimulus object while touching it as a measure. During the familiarization phase, participants were presented with four familiarization objects from one of three categories (e.g. mammals). Then, they were tested with a pair of novel objects, one was a familiar-category object and another was a novel-category object (e.g. vehicle) in the test phase. The chimpanzee infants did not show significant habituation, whereas human infants did. However, most important, both species showed significant novelty-preference in the test phase. This indicates that not only human infants, but also chimpanzee infants formed categorical representations of a global-like level. Implications for the shared origins and species-specificity of categorization abilities, and the cognitive operations underlying categorization, are discussed.

  9. Expression of calcium-binding proteins and selected neuropeptides in the human, chimpanzee, and crab-eating macaque claustrum

    Directory of Open Access Journals (Sweden)

    Andrea ePirone

    2014-05-01

    Full Text Available The claustrum is present in all mammalian species examined so far and its morphology, chemoarchitecture, physiology, phylogenesis and ontogenesis are still a matter of debate. Several morphologically distinct types of immunostained cells were described in different mammalian species. To date, a comparative study on the neurochemical organization of the human and non-human primates claustrum has not been fully described yet, partially due to technical reasons linked to the postmortem sampling interval. The present study analyzes the localization and morphology of neurons expressing parvalbumin (PV, calretinin (CR, NPY, and somatostatin (SOM in the claustrum of man (# 5, chimpanzee (# 1 and crab-eating monkey (#3. Immunoreactivity for the used markers was observed in neuronal cell bodies and processes distributed throughout the anterior-posterior extent of human, chimpanzee and macaque claustrum. Both CR- and PV-immunoreactive (ir neurons were mostly localized in the central and ventral region of the claustrum of the three species while SOM- and NPY-ir neurons seemed to be equally distributed throughout the ventral-dorsal extent. In the chimpanzee claustrum SOM-ir elements were not observed. No co-localization of PV with CR was found, thus suggesting the existence of two non-overlapping populations of PV and CR-ir interneurons. The expression of most proteins (CR, PV, NPY, was similar in all species. The only exception was the absence of SOM-ir elements in the claustrum of the chimpanzee, likely due to species specific variability. Our data suggest a possible common structural organization shared with the adjacent insular region, a further element that emphasizes a possible common ontogeny of the claustrum and the neocortex.

  10. Characterization of a chromosome-specific chimpanzee alpha satellite subset: Evolutionary relationship to subsets on human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Warburton, P.E.; Gosden, J.; Lawson, D. [Western General Hospital, Edinburgh (United Kingdom)] [and others

    1996-04-15

    Alpha satellite DNA is a tandemly repeated DNA family found at the centromeres of all primate chromosomes examined. The fundamental repeat units of alpha satellite DNA are diverged 169- to 172-bp monomers, often found to be organized in chromosome-specific higher-order repeat units. The chromosomes of human (Homo sapiens (HSA)), chimpanzee (Pan troglodytes (PTR) and Pan paniscus), and gorilla (Gorilla gorilla) share a remarkable similarity and synteny. It is of interest to ask if alpha satellite arrays at centromeres of homologous chromosomes between these species are closely related (evolving in an orthologous manner) or if the evolutionary processes that homogenize and spread these arrays within and between chromosomes result in nonorthologous evolution of arrays. By using PCR primers specific for human chromosome 17-specific alpha satellite DNA, we have amplified, cloned, and characterized a chromosome-specific subset from the PTR chimpanzee genome. Hybridization both on Southern blots and in situ as well as sequence analysis show that this subset is most closely related, as expected, to sequences on HSA 17. However, in situ hybridization reveals that this subset is not found on the homologous chromosome in chimpanzee (PTR 19), but instead on PTR 12, which is homologous to HSA 2p. 40 refs., 3 figs.

  11. How comparative psychology can shed light on human evolution: Response to Beran et al.'s discussion of "Cognitive capacities for cooking in chimpanzees".

    Science.gov (United States)

    Rosati, Alexandra G; Warneken, Felix

    2016-06-01

    We recently reported a study (Warneken & Rosati Proceedings of the Royal Society B, 282, 20150229, 2015) examining whether chimpanzees possess several cognitive capacities that are critical to engage in cooking. In a subsequent commentary, Beran, Hopper, de Waal, Sayers, and Brosnan Learning & Behavior (2015) asserted that our paper has several flaws. Their commentary (1) critiques some aspects of our methodology and argues that our work does not constitute evidence that chimpanzees can actually cook; (2) claims that these results are old news, as previous work had already demonstrated that chimpanzees possess most or all of these capacities; and, finally, (3) argues that comparative psychological studies of chimpanzees cannot adequately address questions about human evolution, anyway. However, their critique of the premise of our study simply reiterates several points we made in the original paper. To quote ourselves: "As chimpanzees neither control fire nor cook food in their natural behavior, these experiments therefore focus not on whether chimpanzees can actually cook food, but rather whether they can apply their cognitive skills to novel problems that emulate cooking" (Warneken & Rosati Proceedings of the Royal Society B, 282, 20150229, 2015, p. 2). Furthermore, the methodological issues they raise are standard points about psychological research with animals-many of which were addressed synthetically across our 9 experiments, or else are orthogonal to our claims. Finally, we argue that comparative studies of extant apes (and other nonhuman species) are a powerful and indispensable method for understanding human cognitive evolution.

  12. Personality in sanctuary-housed chimpanzees: A comparative approach of psychobiological and penta-factorial human models.

    Science.gov (United States)

    Úbeda, Yulán; Llorente, Miquel

    2015-02-18

    We evaluate a sanctuary chimpanzee sample (N = 11) using two adapted human assessment instruments: the Five-Factor Model (FFM) and Eysenck's Psychoticism-Extraversion-Neuroticism (PEN) model. The former has been widely used in studies of animal personality, whereas the latter has never been used to assess chimpanzees. We asked familiar keepers and scientists (N = 28) to rate 38 (FFM) and 12 (PEN) personality items. The personality surveys showed reliability in all of the items for both instruments. These were then analyzed in a principal component analysis and a regularized exploratory factor analysis, which revealed four and three components, respectively. The results indicate that both questionnaires show a clear factor structure, with characteristic factors not just for the species, but also for the sample type. However, due to its brevity, the PEN may be more suitable for assessing personality in a sanctuary, where employees do not have much time to devote to the evaluation process. In summary, both models are sensitive enough to evaluate the personality of a group of chimpanzees housed in a sanctuary.

  13. Ontogenetic study of the skull in modern humans and the common chimpanzees: neotenic hypothesis reconsidered with a tridimensional Procrustes analysis.

    Science.gov (United States)

    Penin, Xavier; Berge, Christine; Baylac, Michel

    2002-05-01

    Heterochronic studies compare ontogenetic trajectories of an organ in different species: here, the skulls of common chimpanzees and modern humans. A growth trajectory requires three parameters: size, shape, and ontogenetic age. One of the great advantages of the Procrustes method is the precise definition of size and shape for whole organs such as the skull. The estimated ontogenetic age (dental stages) is added to the plot to give a graphical representation to compare growth trajectories. We used the skulls of 41 Homo sapiens and 50 Pan troglodytes at various stages of growth. The Procrustes superimposition of all specimens was completed by statistical procedures (principal component analysis, multivariate regression, and discriminant function) to calculate separately size-related shape changes (allometry common to chimpanzees and humans), and interspecific shape differences (discriminant function). The results confirm the neotenic theory of the human skull (sensu Gould [1977] Ontogeny and Phylogeny, Cambridge: Harvard University Press; Alberch et al. [1979] Paleobiology 5:296-317), but modify it slightly. Human growth is clearly retarded in terms of both the magnitude of changes (size-shape covariation) and shape alone (size-shape dissociation) with respect to the chimpanzees. At the end of growth, the adult skull in humans reaches an allometric shape (size-related shape) which is equivalent to that of juvenile chimpanzees with no permanent teeth, and a size which is equivalent to that of adult chimpanzees. Our results show that human neoteny involves not only shape retardation (paedomorphosis), but also changes in relative growth velocity. Before the eruption of the first molar, human growth is accelerated, and then strongly decelerated, relative to the growth of the chimpanzee as a reference. This entails a complex process, which explains why these species reach the same overall (i.e., brain + face) size in adult stage. The neotenic traits seem to concern

  14. Shared human-chimpanzee pattern of perinatal femoral shaft morphology and its implications for the evolution of hominin locomotor adaptations.

    Directory of Open Access Journals (Sweden)

    Naoki Morimoto

    Full Text Available Acquisition of bipedality is a hallmark of human evolution. How bipedality evolved from great ape-like locomotor behaviors, however, is still highly debated. This is mainly because it is difficult to infer locomotor function, and even more so locomotor kinematics, from fossil hominin long bones. Structure-function relationships are complex, as long bone morphology reflects phyletic history, developmental programs, and loading history during an individual's lifetime. Here we discriminate between these factors by investigating the morphology of long bones in fetal and neonate great apes and humans, before the onset of locomotion.Comparative morphometric analysis of the femoral diaphysis indicates that its morphology reflects phyletic relationships between hominoid taxa to a greater extent than taxon-specific locomotor adaptations. Diaphyseal morphology in humans and chimpanzees exhibits several shared-derived features, despite substantial differences in locomotor adaptations. Orangutan and gorilla morphologies are largely similar, and likely represent the primitive hominoid state.These findings are compatible with two possible evolutionary scenarios. Diaphyseal morphology may reflect retained adaptive traits of ancestral taxa, hence human-chimpanzee shared-derived features may be indicative of the locomotor behavior of our last common ancestor. Alternatively, diaphyseal morphology might reflect evolution by genetic drift (neutral evolution rather than selection, and might thus be more informative about phyletic relationships between taxa than about locomotor adaptations. Both scenarios are consistent with the hypothesis that knuckle-walking in chimpanzees and gorillas resulted from convergent evolution, and that the evolution of human bipedality is unrelated to extant great ape locomotor specializations.

  15. Animal culture: chimpanzee conformity?

    Science.gov (United States)

    van Schaik, Carel P

    2012-05-22

    Culture-like phenomena in wild animals have received much attention, but how good is the evidence and how similar are they to human culture? New data on chimpanzees suggest their culture may even have an element of conformity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Evolution of life history and behavior in Hominidae: towards phylogenetic reconstruction of the chimpanzee-human last common ancestor.

    Science.gov (United States)

    Duda, Pavel; Zrzavý, Jan

    2013-10-01

    The origin of the fundamental behavioral differences between humans and our closest living relatives is one of the central issues of evolutionary anthropology. The prominent, chimpanzee-based referential model of early hominin behavior has recently been challenged on the basis of broad multispecies comparisons and newly discovered fossil evidence. Here, we argue that while behavioral data on extant great apes are extremely relevant for reconstruction of ancestral behaviors, these behaviors should be reconstructed trait by trait using formal phylogenetic methods. Using the widely accepted hominoid phylogenetic tree, we perform a series of character optimization analyses using 65 selected life-history and behavioral characters for all extant hominid species. This analysis allows us to reconstruct the character states of the last common ancestors of Hominoidea, Hominidae, and the chimpanzee-human last common ancestor. Our analyses demonstrate that many fundamental behavioral and life-history attributes of hominids (including humans) are evidently ancient and likely inherited from the common ancestor of all hominids. However, numerous behaviors present in extant great apes represent their own terminal autapomorphies (both uniquely derived and homoplastic). Any evolutionary model that uses a single extant species to explain behavioral evolution of early hominins is therefore of limited use. In contrast, phylogenetic reconstruction of ancestral states is able to provide a detailed suite of behavioral, ecological and life-history characters for each hypothetical ancestor. The living great apes therefore play an important role for the confident identification of the traits found in the chimpanzee-human last common ancestor, some of which are likely to represent behaviors of the fossil hominins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22

    Directory of Open Access Journals (Sweden)

    Volfovsky Natalia

    2009-01-01

    Full Text Available Abstract Background Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes. Results Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb region, (ii those with at least one exact copy found nearby, and (iii those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429 were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans. Conclusion Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are

  18. A comparative analysis of viral peptides presented by contemporary human and chimpanzee MHC class I molecules

    NARCIS (Netherlands)

    van Deutekom, Hanneke W. M.; Hoof, Ilka; Bontrop, Ronald E.; Keşmir, Can

    2011-01-01

    Genetic factors such as the MHC influence the immunocompetence of an individual. MHC genes are the most polymorphic genes in primates, which is often interpreted as an adaptation to establish good T cell responses to a wide range of (evolving) pathogens. Chimpanzee MHC (Patr) genes are less

  19. Functional Analysis and Treatment of Human-Directed Undesirable Behavior Exhibited by a Captive Chimpanzee

    Science.gov (United States)

    Martin, Allison L.; Bloomsmith, Mollie A.; Kelley, Michael E.; Marr, M. Jackson; Maple, Terry L.

    2011-01-01

    A functional analysis identified the reinforcer maintaining feces throwing and spitting exhibited by a captive adult chimpanzee ("Pan troglodytes"). The implementation of a function-based treatment combining extinction with differential reinforcement of an alternate behavior decreased levels of inappropriate behavior. These findings further…

  20. Initial Description of a Quantitative, Cross-Species (Chimpanzee-Human) Social Responsiveness Measure

    Science.gov (United States)

    Marrus, Natasha; Faughn, Carley; Shuman, Jeremy; Petersen, Steve E.; Constantino, John N.; Povinelli, Daniel J.; Pruett, John R., Jr.

    2011-01-01

    Objective: Comparative studies of social responsiveness, an ability that is impaired in autism spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species…

  1. Perceived differences between chimpanzee (Pan troglodytes) and human (Homo sapiens) facial expressions are related to emotional interpretation.

    Science.gov (United States)

    Waller, Bridget M; Bard, Kim A; Vick, Sarah-Jane; Smith Pasqualini, Marcia C

    2007-11-01

    Human face perception is a finely tuned, specialized process. When comparing faces between species, therefore, it is essential to consider how people make these observational judgments. Comparing facial expressions may be particularly problematic, given that people tend to consider them categorically as emotional signals, which may affect how accurately specific details are processed. The bared-teeth display (BT), observed in most primates, has been proposed as a homologue of the human smile (J. A. R. A. M. van Hooff, 1972). In this study, judgments of similarity between BT displays of chimpanzees (Pan troglodytes) and human smiles varied in relation to perceived emotional valence. When a chimpanzee BT was interpreted as fearful, observers tended to underestimate the magnitude of the relationship between certain features (the extent of lip corner raise) and human smiles. These judgments may reflect the combined effects of categorical emotional perception, configural face processing, and perceptual organization in mental imagery and may demonstrate the advantages of using standardized observational methods in comparative facial expression research. Copyright 2007 APA.

  2. Chimpanzees help each other upon request.

    Directory of Open Access Journals (Sweden)

    Shinya Yamamoto

    2009-10-01

    Full Text Available The evolution of altruism has been explained mainly from ultimate perspectives. However, it remains to be investigated from a proximate point of view how and in which situations such social propensity is achieved. We investigated chimpanzees' targeted helping in a tool transfer paradigm, and discuss the similarities and differences in altruism between humans and chimpanzees. Previously it has been suggested that chimpanzees help human experimenters by retrieving an object which the experimenter is trying to reach. In the present study, we investigated the importance of communicative interactions between chimpanzees themselves and the influence of conspecific partner's request on chimpanzees' targeted helping.We presented two tool-use situations (a stick-use situation and a straw-use situation in two adjacent booths, and supplied non-corresponding tools to paired chimpanzees in the two booths. For example, a chimpanzee in the stick-use situation was supplied with a straw, and the partner in the straw-use situation possessed a stick. Spontaneous tool transfer was observed between paired chimpanzees. The tool transfer events occurred predominantly following recipients' request. Even without any hope of reciprocation from the partner, the chimpanzees continued to help the partner as long as the partner required help.These results provide further evidence for altruistic helping in chimpanzees in the absence of direct personal gain or even immediate reciprocation. Our findings additionally highlight the importance of request as a proximate mechanism motivating prosocial behavior in chimpanzees whether between kin or non-kin individuals and the possible confounding effect of dominance on the symmetry of such interactions. Finally, in contrast to humans, our study suggests that chimpanzees rarely perform acts of voluntary altruism. Voluntary altruism in chimpanzees is not necessarily prompted by simple observation of another's struggle to attain a goal

  3. The genomic distribution of intraspecific and interspecific sequence divergence of human segmental duplications relative to human/chimpanzee chromosomal rearrangements

    Directory of Open Access Journals (Sweden)

    Eichler Evan E

    2008-08-01

    Full Text Available Abstract Background It has been suggested that chromosomal rearrangements harbor the molecular footprint of the biological phenomena which they induce, in the form, for instance, of changes in the sequence divergence rates of linked genes. So far, all the studies of these potential associations have focused on the relationship between structural changes and the rates of evolution of single-copy DNA and have tried to exclude segmental duplications (SDs. This is paradoxical, since SDs are one of the primary forces driving the evolution of structure and function in our genomes and have been linked not only with novel genes acquiring new functions, but also with overall higher DNA sequence divergence and major chromosomal rearrangements. Results Here we take the opposite view and focus on SDs. We analyze several of the features of SDs, including the rates of intraspecific divergence between paralogous copies of human SDs and of interspecific divergence between human SDs and chimpanzee DNA. We study how divergence measures relate to chromosomal rearrangements, while considering other factors that affect evolutionary rates in single copy DNA. Conclusion We find that interspecific SD divergence behaves similarly to divergence of single-copy DNA. In contrast, old and recent paralogous copies of SDs do present different patterns of intraspecific divergence. Also, we show that some relatively recent SDs accumulate in regions that carry inversions in sister lineages.

  4. Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees (Pan troglodytes, Bonobos (Pan paniscus, and Humans (Homo sapiens

    Directory of Open Access Journals (Sweden)

    J. M. Potau

    2018-01-01

    Full Text Available We have analyzed anatomic variations in the pectoralis major and pectoralis minor muscles of common chimpanzees (Pan troglodytes and bonobos (Pan paniscus and compared them to anatomic variations in these muscles in humans (Homo sapiens. We have macroscopically dissected these muscles in six adult Pan troglodytes, five Pan paniscus of ages ranging from fetus to adult, and five adult Homo sapiens. Although Pan troglodytes are thought to lack a separate pectoralis abdominis muscle, we have identified this muscle in three of the Pan troglodytes; none of the Pan paniscus, however, had this muscle. We have also found deep supernumerary fascicles in the pectoralis major of two Pan troglodytes and all five Pan paniscus. In all six Pan troglodytes, the pectoralis minor was inserted at the supraspinatus tendon, while, in Pan paniscus and Homo sapiens, it was inserted at the coracoid process of the scapula. Some of the anatomic features and variations of these muscles in common chimpanzees and bonobos are similar to those found in humans, therefore enhancing our knowledge of primate comparative anatomy and evolution and also shedding light on several clinical issues.

  5. Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees (Pan troglodytes), Bonobos (Pan paniscus), and Humans (Homo sapiens).

    Science.gov (United States)

    Potau, J M; Arias-Martorell, J; Bello-Hellegouarch, G; Casado, A; Pastor, J F; de Paz, F; Diogo, R

    2018-01-01

    We have analyzed anatomic variations in the pectoralis major and pectoralis minor muscles of common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) and compared them to anatomic variations in these muscles in humans (Homo sapiens) . We have macroscopically dissected these muscles in six adult Pan troglodytes , five Pan paniscus of ages ranging from fetus to adult, and five adult Homo sapiens . Although Pan troglodytes are thought to lack a separate pectoralis abdominis muscle, we have identified this muscle in three of the Pan troglodytes ; none of the Pan paniscus , however, had this muscle. We have also found deep supernumerary fascicles in the pectoralis major of two Pan troglodytes and all five Pan paniscus . In all six Pan troglodytes , the pectoralis minor was inserted at the supraspinatus tendon, while, in Pan paniscus and Homo sapiens , it was inserted at the coracoid process of the scapula. Some of the anatomic features and variations of these muscles in common chimpanzees and bonobos are similar to those found in humans, therefore enhancing our knowledge of primate comparative anatomy and evolution and also shedding light on several clinical issues.

  6. In vivo activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee

    NARCIS (Netherlands)

    R. Heijtink; W. Paulij; P.A.C. van Bergen (Patrick); M.H. van Roosmalen (Mark); D. Rohm; B. Eichentopf (Bertram); E. Muchmore; A.D.M.E. Osterhaus (Albert); R.A. de Man (Robert)

    1999-01-01

    textabstractA 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks

  7. Increased neutralization sensitivity and reduced replicative capacity of human immunodeficiency virus type 1 after short-term in vivo or in vitro passage through chimpanzees

    NARCIS (Netherlands)

    Beaumont, T.; Broersen, S.; van Nuenen, A.; Huisman, H. G.; de Roda Husman, A. M.; Heeney, J. L.; Schuitemaker, H.

    2000-01-01

    Development of disease is extremely rare in chimpanzees when inoculated with either T-cell-line-adapted neutralization-sensitive or primary human immunodeficiency virus type 1 (HIV-1), at first excluding a role for HIV-1 neutralization sensitivity in the clinical course of infection. Interestingly,

  8. Chimpanzee Food Preferences, Associative Learning, and the Origins of Cooking

    Science.gov (United States)

    Beran, Michael J.; Hopper, Lydia M.; de Waal, Frans B.M.; Sayers, Ken; Brosnan, Sarah F.

    2015-01-01

    A recent report suggested that chimpanzees demonstrate the cognitive capacities necessary to understand cooking (Warneken & Rosati, 2015). We offer alternate explanations and mechanisms that could account for the behavioral responses of those chimpanzees without invoking the understanding of cooking as a process. We discuss broader issues surrounding the use of chimpanzees in modeling hominid behavior and understanding aspects of human evolution. PMID:26659967

  9. Chimpanzee Food Preferences, Associative Learning, and the Origins of Cooking

    OpenAIRE

    Beran, Michael J.; Hopper, Lydia M.; de Waal, Frans B.M.; Sayers, Ken; Brosnan, Sarah F.

    2016-01-01

    A recent report suggested that chimpanzees demonstrate the cognitive capacities necessary to understand cooking (Warneken & Rosati, 2015). We offer alternate explanations and mechanisms that could account for the behavioral responses of those chimpanzees without invoking the understanding of cooking as a process. We discuss broader issues surrounding the use of chimpanzees in modeling hominid behavior and understanding aspects of human evolution.

  10. Chimpanzee food preferences, associative learning, and the origins of cooking.

    Science.gov (United States)

    Beran, Michael J; Hopper, Lydia M; de Waal, Frans B M; Sayers, Ken; Brosnan, Sarah F

    2016-06-01

    A recent report suggested that chimpanzees demonstrate the cognitive capacities necessary to understand cooking (Warneken & Rosati, 2015). We offer alternate explanations and mechanisms that could account for the behavioral responses of those chimpanzees, without invoking the understanding of cooking as a process. We discuss broader issues surrounding the use of chimpanzees in modeling hominid behavior and understanding aspects of human evolution.

  11. Extensive X-linked adaptive evolution in central chimpanzees

    DEFF Research Database (Denmark)

    Hvilsom, Christina; Qian, Yu; Bataillon, Thomas

    2012-01-01

    on the dominance of beneficial (adaptive) and deleterious mutations. Here we capture and sequence the complete exomes of 12 chimpanzees and present the largest set of protein-coding polymorphism to date. We report extensive adaptive evolution specifically targeting the X chromosome of chimpanzees with as much...... to humans, we find that purifying selection is stronger on the X chromosome than on the autosomes in chimpanzees. We therefore conclude that most adaptive mutations are recessive. We also document dramatically reduced synonymous diversity in the chimpanzee X chromosome relative to autosomes and stronger...... purifying selection than for the human X chromosome. If similar processes were operating in the human-chimpanzee ancestor as in central chimpanzees today, our results therefore provide an explanation for the much-discussed reduction in the human-chimpanzee divergence at the X chromosome....

  12. Chimpanzee Social Responsiveness Scale (CSRS) Detects Individual Variation in Social Responsiveness for Captive Chimpanzees

    Science.gov (United States)

    Faughn, Carley; Marrus, Natasha; Pruett, John R.; Shuman, Jeremy; Ross, Stephen R.; Constantino, John N.; Povinelli, Daniel J.

    2017-01-01

    Comparative studies of social responsiveness, a core impairment in autism spectrum disorder (ASD), will enhance our understanding of typical and atypical social behavior. We previously reported a quantitative, cross-species (human–chimpanzee) social responsiveness measure, which included the development of the Chimpanzee Social Responsiveness Scale (CSRS). Here, we augment our prior CSRS sample with 25 zoo chimpanzees at three sites: combined N = 54. The CSRS demonstrated strong interrater reliability, and low-ranked chimpanzees, on average, displayed higher CSRS scores. The CSRS continues to discriminate variation in chimpanzee social responsiveness, and the association of higher scores with lower chimpanzee social standing has implications for the relationship between autistic traits and human social status. Continued comparative investigations of social responsiveness will enhance our understanding of underlying impairments in ASD, improve early diagnosis, and inform future therapies. PMID:25312279

  13. New Insights into the Evolution of the Human Diet from Faecal Biomarker Analysis in Wild Chimpanzee and Gorilla Faeces.

    Directory of Open Access Journals (Sweden)

    Ainara Sistiaga

    Full Text Available Our understanding of early human diets is based on reconstructed biomechanics of hominin jaws, bone and teeth isotopic data, tooth wear patterns, lithic, taphonomic and zooarchaeological data, which do not provide information about the relative amounts of different types of foods that contributed most to early human diets. Faecal biomarkers are proving to be a valuable tool in identifying relative proportions of plant and animal tissues in Palaeolithic diets. A limiting factor in the application of the faecal biomarker approach is the striking absence of data related to the occurrence of faecal biomarkers in non-human primate faeces. In this study we explored the nature and proportions of sterols and stanols excreted by our closest living relatives. This investigation reports the first faecal biomarker data for wild chimpanzee (Pan troglodytes and mountain gorilla (Gorilla beringei. Our results suggest that the chemometric analysis of faecal biomarkers is a useful tool for distinguishing between NHP and human faecal matter, and hence, it could provide information for palaeodietary research and early human diets.

  14. New Insights into the Evolution of the Human Diet from Faecal Biomarker Analysis in Wild Chimpanzee and Gorilla Faeces.

    Science.gov (United States)

    Sistiaga, Ainara; Wrangham, Richard; Rothman, Jessica M; Summons, Roger E

    2015-01-01

    Our understanding of early human diets is based on reconstructed biomechanics of hominin jaws, bone and teeth isotopic data, tooth wear patterns, lithic, taphonomic and zooarchaeological data, which do not provide information about the relative amounts of different types of foods that contributed most to early human diets. Faecal biomarkers are proving to be a valuable tool in identifying relative proportions of plant and animal tissues in Palaeolithic diets. A limiting factor in the application of the faecal biomarker approach is the striking absence of data related to the occurrence of faecal biomarkers in non-human primate faeces. In this study we explored the nature and proportions of sterols and stanols excreted by our closest living relatives. This investigation reports the first faecal biomarker data for wild chimpanzee (Pan troglodytes) and mountain gorilla (Gorilla beringei). Our results suggest that the chemometric analysis of faecal biomarkers is a useful tool for distinguishing between NHP and human faecal matter, and hence, it could provide information for palaeodietary research and early human diets.

  15. Mouse Chromosome Engineering for Modeling Human Disease

    OpenAIRE

    van der Weyden, Louise; Bradley, Allan

    2006-01-01

    Chromosomal rearrangements occur frequently in humans and can be disease-associated or phenotypically neutral. Recent technological advances have led to the discovery of copy-number changes previously undetected by cytogenetic techniques. To understand the genetic consequences of such genomic changes, these mutations need to be modeled in experimentally tractable systems. The mouse is an excellent organism for this analysis because of its biological and genetic similarity to humans, and the e...

  16. Cognitive capacities for cooking in chimpanzees

    OpenAIRE

    Warneken, Felix; Rosati, Alexandra G.

    2015-01-01

    The transition to a cooked diet represents an important shift in human ecology and evolution. Cooking requires a set of sophisticated cognitive abilities, including causal reasoning, self-control and anticipatory planning. Do humans uniquely possess the cognitive capacities needed to cook food? We address whether one of humans' closest relatives, chimpanzees (Pan troglodytes), possess the domain-general cognitive skills needed to cook. Across nine studies, we show that chimpanzees: (i) prefer...

  17. Brief Report: Chimpanzee Social Responsiveness Scale (CSRS) Detects Individual Variation in Social Responsiveness for Captive Chimpanzees

    Science.gov (United States)

    Faughn, Carley; Marrus, Natasha; Shuman, Jeremy; Ross, Stephen R.; Constantino, John N.; Pruett, John R., Jr.; Povinelli, Daniel J.

    2015-01-01

    Comparative studies of social responsiveness, a core impairment in autism spectrum disorder (ASD), will enhance our understanding of typical and atypical social behavior. We previously reported a quantitative, cross-species (human-chimpanzee) social responsiveness measure, which included the development of the Chimpanzee Social Responsiveness…

  18. Wild chimpanzees are infected by Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Jirků, M.; Votýpka, J.; Petrželková, Klára Judita; Jirků-Pomajbíková, K.; Kriegová, E.; Vodička, R.; Lankester, F.; Leendertz, S. A. J.; Wittig, R. M.; Boesch, C.; Modrý, D.; Ayala, F. J.; Leendertz, F. H.; Lukeš, J.

    2015-01-01

    Roč. 4, č. 3 (2015), s. 277-282 ISSN 0020-7519 Institutional support: RVO:68081766 Keywords : Trypanosomes * Chimpanzee * Non-human primates * Transmission * Diagnostics Subject RIV: EG - Zoology Impact factor: 4.242, year: 2015

  19. Spontaneous altruism by chimpanzees and young children.

    Directory of Open Access Journals (Sweden)

    Felix Warneken

    2007-07-01

    Full Text Available People often act on behalf of others. They do so without immediate personal gain, at cost to themselves, and even toward unfamiliar individuals. Many researchers have claimed that such altruism emanates from a species-unique psychology not found in humans' closest living evolutionary relatives, such as the chimpanzee. In favor of this view, the few experimental studies on altruism in chimpanzees have produced mostly negative results. In contrast, we report experimental evidence that chimpanzees perform basic forms of helping in the absence of rewards spontaneously and repeatedly toward humans and conspecifics. In two comparative studies, semi-free ranging chimpanzees helped an unfamiliar human to the same degree as did human infants, irrespective of being rewarded (experiment 1 or whether the helping was costly (experiment 2. In a third study, chimpanzees helped an unrelated conspecific gain access to food in a novel situation that required subjects to use a newly acquired skill on behalf of another individual. These results indicate that chimpanzees share crucial aspects of altruism with humans, suggesting that the roots of human altruism may go deeper than previous experimental evidence suggested.

  20. Specificity of chimpanzee antibodies binding a strain-specific HIV-1 neutralization epitope of the external envelope

    NARCIS (Netherlands)

    Goudsmit, J.; Bakker, M.; Smit, L.; Meloen, R. H.

    1989-01-01

    Sera from three chimpanzees infected with a primary lymphadenopathy-associated virus (LAV-1) or human T-lymphotropic virus type III (HTLV-IIIB) passage, from two chimpanzees infected with blood from the primary infected chimpanzees, and from one chimpanzee infected with blood from a secondary

  1. Do wild chimpanzee populations develop diverse cultures? [Latest Thinking

    OpenAIRE

    Boesch, C.

    2017-01-01

    Humans pride themselves on having extensive and diverse cultures. However, cultures can also be observed in animals. The research presented in this video aims at understanding the cultures of wild chimpanzee populations in several African countries and how they differ from each other. As chimpanzees avoid human contact, CHRISTOPHE BOESCH explains, the research team conducted the study by setting up camera traps to catch chimpanzee behavior on video. Forty locations were carefully selected to ...

  2. Mouse models for understanding human developmental anomalies

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1989-01-01

    The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals

  3. Signs of mood and anxiety disorders in chimpanzees.

    Directory of Open Access Journals (Sweden)

    Hope R Ferdowsian

    Full Text Available BACKGROUND: In humans, traumatic experiences are sometimes followed by psychiatric disorders. In chimpanzees, studies have demonstrated an association between traumatic events and the emergence of behavioral disturbances resembling posttraumatic stress disorder (PTSD and depression. We addressed the following central question: Do chimpanzees develop posttraumatic symptoms, in the form of abnormal behaviors, which cluster into syndromes similar to those described in human mood and anxiety disorders? METHODOLOGY/PRINCIPAL FINDINGS: In phase 1 of this study, we accessed case reports of chimpanzees who had been reportedly subjected to traumatic events, such as maternal separation, social isolation, experimentation, or similar experiences. We applied and tested DSM-IV criteria for PTSD and major depression to published case reports of 20 chimpanzees identified through PrimateLit. Additionally, using the DSM-IV criteria and ethograms as guides, we developed behaviorally anchored alternative criteria that were applied to the case reports. A small number of chimpanzees in the case studies met DSM-IV criteria for PTSD and depression. Measures of inter-rater reliability, including Fleiss' kappa and percentage agreement, were higher with use of the alternative criteria for PTSD and depression. In phase 2, the alternative criteria were applied to chimpanzees living in wild sites in Africa (n = 196 and chimpanzees living in sanctuaries with prior histories of experimentation, orphanage, illegal seizure, or violent human conflict (n = 168. In phase 2, 58% of chimpanzees living in sanctuaries met the set of alternative criteria for depression, compared with 3% of chimpanzees in the wild (p = 0.04, and 44% of chimpanzees in sanctuaries met the set of alternative criteria for PTSD, compared with 0.5% of chimpanzees in the wild (p = 0.04. CONCLUSIONS/SIGNIFICANCE: Chimpanzees display behavioral clusters similar to PTSD and depression in their key

  4. A Mouse Model for Human Anal Cancer

    Science.gov (United States)

    Stelzer, Marie K.; Pitot, Henry C.; Liem, Amy; Schweizer, Johannes; Mahoney, Charles; Lambert, Paul F.

    2010-01-01

    Human anal cancers are associated with high-risk human papillomaviruses (HPVs) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including but not limited to their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors; whereas, none of the like treated non-transgenic mice showed tumors. Histopathological analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. PMID:20947489

  5. Humanized Mouse Models of Staphylococcus aureus Infection

    Directory of Open Access Journals (Sweden)

    Dane Parker

    2017-05-01

    Full Text Available Staphylococcus aureus is a successful human pathogen that has adapted itself in response to selection pressure by the human immune system. A commensal of the human skin and nose, it is a leading cause of several conditions: skin and soft tissue infection, pneumonia, septicemia, peritonitis, bacteremia, and endocarditis. Mice have been used extensively in all these conditions to identify virulence factors and host components important for pathogenesis. Although significant effort has gone toward development of an anti-staphylococcal vaccine, antibodies have proven ineffective in preventing infection in humans after successful studies in mice. These results have raised questions as to the utility of mice to predict patient outcome and suggest that humanized mice might prove useful in modeling infection. The development of humanized mouse models of S. aureus infection will allow us to assess the contribution of several human-specific virulence factors, in addition to exploring components of the human immune system in protection against S. aureus infection. Their use is discussed in light of several recently reported studies.

  6. Tool-use in excavation of underground food by captive chimpanzees (Pan troglodytes): Implication for wild chimpanzee behavior

    OpenAIRE

    Majlesi, Parandis

    2014-01-01

    Extractive foraging of underground storage organs (USOs) is believed to have played an important role in human evolution. This behavior is also present in wild chimpanzees (Pan troglodytes), who sometimes use tools in the task. Despite the importance of studying this behavior in chimpanzees to model how early hominins may have used tools in the context of USO excavation, it remains to be directly observed due to the chimpanzees lack of habituation in the two study sites that yielded evidence...

  7. Chimpanzee drumming : a spontaneous performance with characteristics of human musical drumming

    NARCIS (Netherlands)

    Dufour, Valerie; Poulin, Nicolas; Cure, Charlotte; Sterck, Elisabeth H. M.

    2015-01-01

    Despite the quintessential role that music plays in human societies by enabling us to release and share emotions with others, traces of its evolutionary origins in other species remain scarce. Drumming like humans whilst producing music is practically unheard of in our most closely related species,

  8. Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content

    NARCIS (Netherlands)

    Hughes, Jennifer F.; Skaletsky, Helen; Pyntikova, Tatyana; Graves, Tina A.; van Daalen, Saskia K. M.; Minx, Patrick J.; Fulton, Robert S.; McGrath, Sean D.; Locke, Devin P.; Friedman, Cynthia; Trask, Barbara J.; Mardis, Elaine R.; Warren, Wesley C.; Repping, Sjoerd; Rozen, Steve; Wilson, Richard K.; Page, David C.

    2010-01-01

    The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome(1,2). Little is known about the recent evolution of the Y chromosome because only

  9. The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

    Science.gov (United States)

    Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

    2015-01-01

    The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. 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.

  11. A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

    Directory of Open Access Journals (Sweden)

    Matthew E. Brown

    2018-04-01

    Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

  12. Evaluation of lung immunity in chimpanzees

    International Nuclear Information System (INIS)

    Bice, D.E.; Harris, D.L.; Muggenburg, B.A.; Bowen, J.A.

    1980-01-01

    The effects of inhaled pollutants on the immune defenses in the lung can be studied in several animal species. To assure that the data obtained can be extrapolated to man, it is essential that the development of lung immunity is similar in the experimental animal selected and in humans. Because of the similarity of immune responses in chimpanzees and in humans, the development of immunity in the chimpanzee after lung immunization was evaluated. The results from the chimpanzees were qualitatively the same as those from previous studies in which single lung lobes of dogs were immunized. It was concluded that immunotoxicology data obtained in dogs can be used to estimate the effects of inhaled pollutants on the immune defense mechanism in the human lung

  13. Np9, a cellular protein of retroviral ancestry restricted to human, chimpanzee and gorilla, binds and regulates ubiquitin ligase MDM2

    Science.gov (United States)

    Heyne, Kristina; Kölsch, Kathrin; Bruand, Marine; Kremmer, Elisabeth; Grässer, Friedrich A; Mayer, Jens; Roemer, Klaus

    2015-01-01

    Humans and primates are long-lived animals with long reproductive phases. One factor that appears to contribute to longevity and fertility in humans, as well as to cancer-free survival, is the transcription factor and tumor suppressor p53, controlled by its main negative regulator MDM2. However, p53 and MDM2 homologs are found throughout the metazoan kingdom from Trichoplacidae to Hominidae. Therefore the question arises, if p53/MDM2 contributes to the shaping of primate features, then through which mechanisms. Previous findings have indicated that the appearances of novel p53-regulated genes and wild-type p53 variants during primate evolution are important in this context. Here, we report on another mechanism of potential relevance. Human endogenous retrovirus K subgroup HML-2 (HERV-K(HML-2)) type 1 proviral sequences were formed in the genomes of the predecessors of contemporary Hominoidea and can be identified in the genomes of Nomascus leucogenys (gibbon) up to Homo sapiens. We previously reported on an alternative splicing event in HERV-K(HML-2) type 1 proviruses that can give rise to nuclear protein of 9 kDa (Np9). We document here the evolution of Np9-coding capacity in human, chimpanzee and gorilla, and show that the C-terminal half of Np9 binds directly to MDM2, through a domain of MDM2 that is known to be contacted by various cellular proteins in response to stress. Np9 can inhibit the MDM2 ubiquitin ligase activity toward p53 in the cell nucleus, and can support the transactivation of genes by p53. Our findings point to the possibility that endogenous retrovirus protein Np9 contributes to the regulation of the p53-MDM2 pathway specifically in humans, chimpanzees and gorillas. PMID:26103464

  14. Chimpanzee malaria parasites related to Plasmodium ovale in Africa.

    Directory of Open Access Journals (Sweden)

    Linda Duval

    Full Text Available Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes.

  15. Chromosomal localization of the human and mouse hyaluronan synthase genes

    Energy Technology Data Exchange (ETDEWEB)

    Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others

    1997-05-01

    We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.

  16. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

    Directory of Open Access Journals (Sweden)

    Katarzyna Bozek

    2014-05-01

    Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

  17. Age-related effects in the neocortical organization of chimpanzees

    DEFF Research Database (Denmark)

    Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine

    2014-01-01

    chimpanzees. We used the BrainVisa software to measure total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index in a cross-sectional sample of 219 captive chimpanzees (8-53 years old), with 38 subjects being 40 or more years of age. Mean depth and cortical fold opening...... of 11 major sulci of the chimpanzee brains were also measured. We found that chimpanzees showed increased gyrification with age and a cubic relationship between age and white matter volume. For the association between age and sulcus depth and width, the results were mostly non......Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray...

  18. Human · mouse genome analysis and radiation biology. Proceedings

    International Nuclear Information System (INIS)

    Hori, Tada-aki

    1994-03-01

    This issue is the collection of the papers presented at the 25th NIRS symposium on Human, Mouse Genome Analysis and Radiation Biology. The 14 of the presented papers are indexed individually. (J.P.N.)

  19. The first chimpanzee sanctuary in Japan: an attempt to care for the "surplus" of biomedical research.

    Science.gov (United States)

    Morimura, Naruki; Idani, Gen'ichi; Matsuzawa, Tetsuro

    2011-03-01

    This article specifically examines several aspects of the human-captive chimpanzee bond and the effort to create the first chimpanzee sanctuary in Japan. We discuss our ethical responsibility for captive chimpanzees that have been used in biomedical research. On April 1, 2007, the Chimpanzee Sanctuary Uto (CSU) was established as the first sanctuary for retired laboratory chimpanzees in Japan. This initiative was the result of the continuous efforts by members of Support for African/Asian Great Apes (SAGA), and the Great Ape Information Network to provide a solution to the large chimpanzee colony held in biomedical facilities. However, the cessation of invasive biomedical studies using chimpanzees has created a new set of challenges because Japan lacks registration and laws banning invasive ape experiments and lacks a national policy for the life-long care of retired laboratory chimpanzees. Therefore, CSU has initiated a relocation program in which 79 retired laboratory chimpanzees will be sent to domestic zoos and receive life-long care. By the end of 2009, the number of chimpanzees living at CSU had decreased from 79 to 59 individuals. A nationwide network of care facilities and CSU to provide life-long care of retired laboratory chimpanzees is growing across Japan. This will result in humane treatment of these research animals. 2010 Wiley-Liss, Inc.

  20. Intergroup aggression in chimpanzees and war in nomadic hunter-gatherers: evaluating the chimpanzee model.

    Science.gov (United States)

    Wrangham, Richard W; Glowacki, Luke

    2012-03-01

    Chimpanzee and hunter-gatherer intergroup aggression differ in important ways, including humans having the ability to form peaceful relationships and alliances among groups. This paper nevertheless evaluates the hypothesis that intergroup aggression evolved according to the same functional principles in the two species-selection favoring a tendency to kill members of neighboring groups when killing could be carried out safely. According to this idea chimpanzees and humans are equally risk-averse when fighting. When self-sacrificial war practices are found in humans, therefore, they result from cultural systems of reward, punishment, and coercion rather than evolved adaptations to greater risk-taking. To test this "chimpanzee model," we review intergroup fighting in chimpanzees and nomadic hunter-gatherers living with other nomadic hunter-gatherers as neighbors. Whether humans have evolved specific psychological adaptations for war is unknown, but current evidence suggests that the chimpanzee model is an appropriate starting point for analyzing the biological and cultural evolution of warfare.

  1. In vitro culture of mouse embryos amniotic fluid ID human

    African Journals Online (AJOL)

    1989-07-15

    Jul 15, 1989 ... Because human amniotic fluid is a physiological, balanced ultrafiltrate, it has been considered as an inexpensive alternative culture medium in. IVF. A study of the development of mouse embryos in human amniotic fluid was undertaken to assess the suitability of this as an optional culture medium in human ...

  2. 'Adoption' by maternal siblings in wild chimpanzees

    NARCIS (Netherlands)

    Hobaiter, Catherine; Schel, Anne Marijke; Langergraber, Kevin; Zuberbühler, Klaus

    2014-01-01

    The adoption of unrelated orphaned infants is something chimpanzees and humans have in common. Providing parental care has fitness implications for both the adopter and orphan, and cases of adoption have thus been cited as evidence for a shared origin of an altruistic behaviour. We provide new data

  3. Bipedal tool use strengthens chimpanzee hand preferences

    DEFF Research Database (Denmark)

    Braccini, Stephanie; Lambeth, Susan; Schapiro, Steve

    2010-01-01

    The degree to which non-human primate behavior is lateralized, at either individual or population levels, remains controversial. We investigated the relationship between hand preference and posture during tool use in chimpanzees (Pan troglodytes) during bipedal tool use. We experimentally induced...

  4. Wild chimpanzees are infected by Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Jirků, Milan; Votýpka, Jan; Petrželková, Klára Judita; Jirků-Pomajbíková, K.; Kriegová, Eva; Vodička, R.; Lankester, F.; Leendertz, S. A. J.; Wittig, R. M.; Boesch, C.; Modrý, David; Ayala, F. J.; Leendertz, F. H.; Lukeš, Julius

    2015-01-01

    Roč. 4, č. 3 (2015), s. 277-282 ISSN 2213-2244 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 EU Projects: European Commission(XE) 316304 Institutional support: RVO:60077344 Keywords : Trypanosomes * Chimpanzee * Non-human primates * Transmission * Diagnostics Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine

  5. Development and function of human innate immune cells in a humanized mouse model.

    Science.gov (United States)

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

    2014-04-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

  6. 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.

  7. Controlled studies of chimpanzee cultural transmission.

    Science.gov (United States)

    Horner, Victoria; de Waal, Frans B M

    2009-01-01

    Following the first long-term field studies of chimpanzees in the 1960s, researchers began to suspect that chimpanzees from different African populations varied in their behavior, and that some of these variations were transmitted through social learning, thus suggesting culture. Additional reports of chimpanzee culture have since accumulated, which involve an increasing amount of behavioral variation that has no obvious ecological or genetic explanation. To date, close to 50 cultural variants have been reported, including subsistence behavior, tool-use, communication signals, and grooming patterns. Nevertheless, field studies lack the experimental controls and manipulations necessary to conclusively demonstrate that the observed variation results from differential invention and social transmission of behavior. This would require that behavioral variants have been learned from others, a question best addressed in a controlled experimental setting. The following chapter details a series of experimental studies at Yerkes National Primate Research Center of Emory University. In each case, the behavior of two captive groups (each N=12 individuals) was compared before and after the introduction of a novel foraging behavior by a trained conspecific "inventor." The studies were designed to investigate (i) the conditions under which chimpanzees learn from one another, (ii) how behaviors are transmitted, (iii) how cultures are maintained over generations. The results emphasize the importance of integrating both fieldwork and experimental approaches. Previous studies have reported deficits in chimpanzees' cultural capacities, but did so after testing them with human models, which are largely irrelevant to the problem at hand. A representative understanding of culture can only be gained when efforts are made to create a naturalistic learning environment in which chimpanzees have opportunities to learn spontaneously from conspecifics in a familiar social setting.

  8. Chimpanzees, cooking, and a more comparative psychology.

    Science.gov (United States)

    Beran, Michael J; Hopper, Lydia M; de Waal, Frans B M; Brosnan, Sarah F; Sayers, Ken

    2016-06-01

    A recent report suggested that chimpanzees demonstrate the cognitive capacities necessary to understand cooking (Warneken & Rosati, 2015). We offered alternative explanations and mechanisms that could account for the behavioral responses of those chimpanzees, and questioned the manner in which the data were used to examine human evolution (Beran, Hopper, de Waal, Sayers, & Brosnan, 2015). Two commentaries suggested either that we were overly critical of the original report's claims and methodology (Rosati & Warneken, 2016), or that, contrary to our statements, early biological thinkers contributed little to questions concerning the evolutionary importance of cooking (Wrangham, 2016). In addition, both commentaries took issue with our treatment of chimpanzee referential models in human evolutionary studies. Our response offers points of continued disagreement as well as points of conciliation. We view Warneken and Rosati's general conclusions as a case of affirming the consequent-a logical conundrum in which, in this case, a demonstration of a partial list of the underlying abilities required for a cognitive trait/suite (understanding of cooking) are suggested as evidence for that ability. And although we strongly concur with both Warneken and Rosati (2015) and Wrangham (2016) that chimpanzee research is invaluable and essential to understanding humanness, it can only achieve its potential via the holistic inclusion of all available evidence-including that from other animals, evolutionary theory, and the fossil and archaeological records.

  9. The mouse-human anatomy ontology mapping project.

    Science.gov (United States)

    Hayamizu, Terry F; de Coronado, Sherri; Fragoso, Gilberto; Sioutos, Nicholas; Kadin, James A; Ringwald, Martin

    2012-01-01

    The overall objective of the Mouse-Human Anatomy Project (MHAP) was to facilitate the mapping and harmonization of anatomical terms used for mouse and human models by Mouse Genome Informatics (MGI) and the National Cancer Institute (NCI). The anatomy resources designated for this study were the Adult Mouse Anatomy (MA) ontology and the set of anatomy concepts contained in the NCI Thesaurus (NCIt). Several methods and software tools were identified and evaluated, then used to conduct an in-depth comparative analysis of the anatomy ontologies. Matches between mouse and human anatomy terms were determined and validated, resulting in a highly curated set of mappings between the two ontologies that has been used by other resources. These mappings will enable linking of data from mouse and human. As the anatomy ontologies have been expanded and refined, the mappings have been updated accordingly. Insights are presented into the overall process of comparing and mapping between ontologies, which may prove useful for further comparative analyses and ontology mapping efforts, especially those involving anatomy ontologies. Finally, issues concerning further development of the ontologies, updates to the mapping files, and possible additional applications and significance were considered. DATABASE URL: http://obofoundry.org/cgi-bin/detail.cgi?id=ma2ncit.

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

    Science.gov (United States)

    Dickman, Amy J

    2012-01-01

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

  11. End Sequencing and Finger Printing of Human & Mouse BAC Libraries

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, C

    2005-09-27

    This project provided for continued end sequencing of existing and new BAC libraries constructed to support human sequencing as well as to initiate BAC end sequencing from the mouse BAC libraries constructed to support mouse sequencing. The clones, the sequences, and the fingerprints are now an available resource for the community at large. Research and development of new metaodologies for BAC end sequencing have reduced costs and increase throughput.

  12. Chimpanzees return favors at a personal cost.

    Science.gov (United States)

    Schmelz, Martin; Grueneisen, Sebastian; Kabalak, Alihan; Jost, Jürgen; Tomasello, Michael

    2017-07-11

    Humans regularly provide others with resources at a personal cost to themselves. Chimpanzees engage in some cooperative behaviors in the wild as well, but their motivational underpinnings are unclear. In three experiments, chimpanzees ( Pan troglodytes ) always chose between an option delivering food both to themselves and a partner and one delivering food only to themselves. In one condition, a conspecific partner had just previously taken a personal risk to make this choice available. In another condition, no assistance from the partner preceded the subject's decision. Chimpanzees made significantly more prosocial choices after receiving their partner's assistance than when no assistance was given (experiment 1) and, crucially, this was the case even when choosing the prosocial option was materially costly for the subject (experiment 2). Moreover, subjects appeared sensitive to the risk of their partner's assistance and chose prosocially more often when their partner risked losing food by helping (experiment 3). These findings demonstrate experimentally that chimpanzees are willing to incur a material cost to deliver rewards to a conspecific, but only if that conspecific previously assisted them, and particularly when this assistance was risky. Some key motivations involved in human cooperation thus may have deeper phylogenetic roots than previously suspected.

  13. Cues to Personality and Health in the Facial Appearance of Chimpanzees (Pan Troglodytes

    Directory of Open Access Journals (Sweden)

    Robin S. S. Kramer

    2012-04-01

    Full Text Available Humans (Homo sapiens and chimpanzees (Pan troglodytes can extract socially-relevant information from the static, non-expressive faces of conspecifics. In humans, the face is a valid signal of both personality and health. Recent evidence shows that, like humans, chimpanzee faces also contain personality information, and that humans can accurately judge aspects of chimpanzee personality relating to extraversion from the face alone (Kramer, King, and Ward, 2011. These findings suggest the hypothesis that humans and chimpanzees share a system of personality and facial morphology for signaling socially-relevant traits from the face. We sought to test this hypothesis using a new group of chimpanzees. In two studies, we found that chimpanzee faces contained health information, as well as information of characteristics relating to extraversion, emotional stability, and agreeableness, using average judgments from pairs of individual photographs. In a third study, information relating to extraversion and health was also present in composite images of individual chimpanzees. We therefore replicate and extend previous findings using a new group of chimpanzees and demonstrate two methods for minimizing the variability associated with individual photographs. Our findings support the hypothesis that chimpanzees and humans share a personality signaling system.

  14. The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

    Science.gov (United States)

    Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

    2017-11-01

    Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

    NARCIS (Netherlands)

    van der Geld, Ymke M.; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G.; Limburg, Pieter C.; Kallenberg, Cees G. M.

    2007-01-01

    Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm,

  16. 'Adoption' by maternal siblings in wild chimpanzees.

    Directory of Open Access Journals (Sweden)

    Catherine Hobaiter

    Full Text Available The adoption of unrelated orphaned infants is something chimpanzees and humans have in common. Providing parental care has fitness implications for both the adopter and orphan, and cases of adoption have thus been cited as evidence for a shared origin of an altruistic behaviour. We provide new data on adoptions in the free-living Sonso chimpanzee community in Uganda, together with an analysis of published data from other long-term field sites. As a default pattern, we find that orphan chimpanzees do not become adopted by adult group members but wherever possible associate with each other, usually as maternal sibling pairs. This occurs even if both partners are still immature, with older individuals effectively becoming 'child household heads'. Adoption of orphans by unrelated individuals does occur but usually only if no maternal siblings or other relatives are present and only after significant delays. In conclusion, following the loss of their mother, orphaned chimpanzees preferentially associate along pre-existing social bonds, which are typically strongest amongst maternal siblings.

  17. Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

    Science.gov (United States)

    Uhl, Elizabeth W; Warner, Natalie J

    Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.

  18. A Guttman-Based Approach to Identifying Cumulativeness Applied to Chimpanzee Culture

    OpenAIRE

    Graber, RB; de Cock, DR; Burton, ML

    2012-01-01

    Human culture appears to build on itself-that is, to be to some extent cumulative. Whether this property is shared by culture in the common chimpanzee is controversial. The question previously has been approached, qualitatively (and inconclusively), by debating whether any chimpanzee culture traits have resulted from individuals building on one another's work ("ratcheting"). The fact that the chimpanzees at different sites have distinctive repertoires of traits affords a different avenue of a...

  19. High diversity at PRDM9 in chimpanzees and bonobos.

    Directory of Open Access Journals (Sweden)

    Linn Fenna Groeneveld

    Full Text Available BACKGROUND: The PRDM9 locus in mammals has increasingly attracted research attention due to its role in mediating chromosomal recombination and possible involvement in hybrid sterility and hence speciation processes. The aim of this study was to characterize sequence variation at the PRDM9 locus in a sample of our closest living relatives, the chimpanzees and bonobos. METHODOLOGY/PRINCIPAL FINDINGS: PRDM9 contains a highly variable and repetitive zinc finger array. We amplified this domain using long-range PCR and determined the DNA sequences using conventional Sanger sequencing. From 17 chimpanzees representing three subspecies and five bonobos we obtained a total of 12 alleles differing at the nucleotide level. Based on a data set consisting of our data and recently published Pan PRDM9 sequences, we found that at the subspecies level, diversity levels did not differ among chimpanzee subspecies or between chimpanzee subspecies and bonobos. In contrast, the sample of chimpanzees harbors significantly more diversity at PRDM9 than samples of humans. Pan PRDM9 shows signs of rapid evolution including no alleles or ZnFs in common with humans as well as signals of positive selection in the residues responsible for DNA binding. CONCLUSIONS AND SIGNIFICANCE: The high number of alleles specific to the genus Pan, signs of positive selection in the DNA binding residues, and reported lack of conservation of recombination hotspots between chimpanzees and humans suggest that PRDM9 could be active in hotspot recruitment in the genus Pan. Chimpanzees and bonobos are considered separate species and do not have overlapping ranges in the wild, making the presence of shared alleles at the amino acid level between the chimpanzee and bonobo species interesting in view of the hypothesis that PRDM9 plays a universal role in interspecific hybrid sterility.

  20. Influence of age, irradiation and humanization on NSG mouse phenotypes

    Directory of Open Access Journals (Sweden)

    Jaclyn S. Knibbe-Hollinger

    2015-10-01

    Full Text Available Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization.

  1. Use of "entertainment" chimpanzees in commercials distorts public perception regarding their conservation status.

    Directory of Open Access Journals (Sweden)

    Kara K Schroepfer

    Full Text Available Chimpanzees (Pan troglodytes are often used in movies, commercials and print advertisements with the intention of eliciting a humorous response from audiences. The portrayal of chimpanzees in unnatural, human-like situations may have a negative effect on the public's understanding of their endangered status in the wild while making them appear as suitable pets. Alternatively, media content that elicits a positive emotional response toward chimpanzees may increase the public's commitment to chimpanzee conservation. To test these competing hypotheses, participants (n = 165 watched a series of commercials in an experiment framed as a marketing study. Imbedded within the same series of commercials was one of three chimpanzee videos. Participants either watched 1 a chimpanzee conservation commercial, 2 commercials containing "entertainment" chimpanzees or 3 control footage of the natural behavior of wild chimpanzees. Results from a post-viewing questionnaire reveal that participants who watched the conservation message understood that chimpanzees were endangered and unsuitable as pets at higher levels than those viewing the control footage. Meanwhile participants watching commercials with entertainment chimpanzees showed a decrease in understanding relative to those watching the control footage. In addition, when participants were given the opportunity to donate part of their earnings from the experiment to a conservation charity, donations were least frequent in the group watching commercials with entertainment chimpanzees. Control questions show that participants did not detect the purpose of the study. These results firmly support the hypothesis that use of entertainment chimpanzees in the popular media negatively distorts the public's perception and hinders chimpanzee conservation efforts.

  2. Social disappointment explains chimpanzees' behaviour in the inequity aversion task.

    Science.gov (United States)

    Engelmann, Jan M; Clift, Jeremy B; Herrmann, Esther; Tomasello, Michael

    2017-08-30

    Chimpanzees' refusal of less-preferred food when an experimenter has previously provided preferred food to a conspecific has been taken as evidence for a sense of fairness. Here, we present a novel hypothesis-the social disappointment hypothesis-according to which food refusals express chimpanzees' disappointment in the human experimenter for not rewarding them as well as they could have. We tested this hypothesis using a two-by-two design in which food was either distributed by an experimenter or a machine and with a partner present or absent. We found that chimpanzees were more likely to reject food when it was distributed by an experimenter rather than by a machine and that they were not more likely to do so when a partner was present. These results suggest that chimpanzees' refusal of less-preferred food stems from social disappointment in the experimenter and not from a sense of fairness. © 2017 The Author(s).

  3. FANTOM5 CAGE profiles of human and mouse samples

    NARCIS (Netherlands)

    Noguchi, Shuhei; Arakawa, Takahiro; Fukuda, Shiro; Furuno, Masaaki; Hasegawa, Akira; Hori, Fumi; Ishikawa-Kato, Sachi; Kaida, Kaoru; Kaiho, Ai; Kanamori-Katayama, Mutsumi; Kawashima, Tsugumi; Kojima, Miki; Kubosaki, Atsutaka; Manabe, Ri-ichiroh; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakazato, Kenichi; Ninomiya, Noriko; Nishiyori-Sueki, Hiromi; Noma, Shohei; Saijyo, Eri; Saka, Akiko; Sakai, Mizuho; Simon, Christophe; Suzuki, Naoko; Tagami, Michihira; Watanabe, Shoko; Yoshida, Shigehiro; Arner, Peter; Axton, Richard A.; Babina, Magda; Baillie, J. Kenneth; Barnett, Timothy C.; Beckhouse, Anthony G.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Carlisle, Ailsa J.; Clevers, Hans C.; Davis, Carrie A.; Detmar, Michael; Dohi, Taeko; Edge, Albert S. B.; Edinger, Matthias; Ehrlund, Anna; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Eslami, Afsaneh; Fagiolini, Michela; Fairbairn, Lynsey; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Ferrai, Carmelo; Fisher, Malcolm E.; Forrester, Lesley M.; Fujita, Rie; Furusawa, Jun-ichi; Geijtenbeek, Teunis B.; Gingeras, Thomas; Goldowitz, Daniel; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J.; Hamaguchi, Masahide; Hara, Mitsuko; Hasegawa, Yuki; Herlyn, Meenhard; Heutink, Peter; Hitchens, Kelly J.; Hume, David A.; Ikawa, Tomokatsu; Ishizu, Yuri; Kai, Chieko; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klein, Sarah; Klinken, S. Peter; Knox, Alan J.; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Lee, Weonju; Lennartsson, Andreas; Mackay-sim, Alan; Mejhert, Niklas; Mizuno, Yosuke; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Morris, Kelly J.; Motohashi, Hozumi; Mummery, Christine L.; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Passier, Robert; Patrikakis, Margaret; Pombo, Ana; Pradhan-Bhatt, Swati; Qin, Xian-Yang; Rehli, Michael; Rizzu, Patrizia; Roy, Sugata; Sajantila, Antti; Sakaguchi, Shimon; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schmidl, Christian; Schneider, Claudio; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sheng, Guojun; Shin, Jay W.; Sugiyama, Daisuke; Sugiyama, Takaaki; Summers, Kim M.; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tomoiu, Andru; Toyoda, Hiroo; van de Wetering, Marc; van den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Yamaguchi, Yoko; Yamamoto, Masayuki; Yanagi-Mizuochi, Chiyo; Yoneda, Misako; Yonekura, Yohei; Zhang, Peter G.; Zucchelli, Silvia; Abugessaisa, Imad; Arner, Erik; Harshbarger, Jayson; Kondo, Atsushi; Lassmann, Timo; Lizio, Marina; Sahin, Serkan; Sengstag, Thierry; Severin, Jessica; Shimoji, Hisashi; Suzuki, Masanori; Suzuki, Harukazu; Kawai, Jun; Kondo, Naoto; Itoh, Masayoshi; Daub, Carsten O.; Kasukawa, Takeya; Kawaji, Hideya; Carninci, Piero; Forrest, Alistair R. R.; Hayashizaki, Yoshihide

    2017-01-01

    In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples,

  4. Study of methyl bromide reactivity with human and mouse hemoglobin

    African Journals Online (AJOL)

    A study has been carried out on in-vitro reactivity of human and mouse hemoglobin spectrophotometrically at physiological pH, using different protein to reagent ratios. Hemoglobin side chains were modified with different concentrations of methyl bromide on agro-soil fumigant. To ascertain if the site of alkylation was the ...

  5. Neural representation of face familiarity in an awake chimpanzee

    Directory of Open Access Journals (Sweden)

    Hirokata Fukushima

    2013-12-01

    Full Text Available Evaluating the familiarity of faces is critical for social animals as it is the basis of individual recognition. In the present study, we examined how face familiarity is reflected in neural activities in our closest living relative, the chimpanzee. Skin-surface event-related brain potentials (ERPs were measured while a fully awake chimpanzee observed photographs of familiar and unfamiliar chimpanzee faces (Experiment 1 and human faces (Experiment 2. The ERPs evoked by chimpanzee faces differentiated unfamiliar individuals from familiar ones around midline areas centered on vertex sites at approximately 200 ms after the stimulus onset. In addition, the ERP response to the image of the subject’s own face did not significantly diverge from those evoked by familiar chimpanzees, suggesting that the subject’s brain at a minimum remembered the image of her own face. The ERPs evoked by human faces were not influenced by the familiarity of target individuals. These results indicate that chimpanzee neural representations are more sensitive to the familiarity of conspecific than allospecific faces.

  6. 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

  7. 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.

  8. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  9. Carboxylesterases in lipid metabolism: from mouse to human

    Directory of Open Access Journals (Sweden)

    Jihong Lian

    2017-07-01

    Full Text Available ABSTRACT Mammalian carboxylesterases hydrolyze a wide range of xenobiotic and endogenous compounds, including lipid esters. Physiological functions of carboxylesterases in lipid metabolism and energy homeostasis in vivo have been demonstrated by genetic manipulations and chemical inhibition in mice, and in vitro through (overexpression, knockdown of expression, and chemical inhibition in a variety of cells. Recent research advances have revealed the relevance of carboxylesterases to metabolic diseases such as obesity and fatty liver disease, suggesting these enzymes might be potential targets for treatment of metabolic disorders. In order to translate pre-clinical studies in cellular and mouse models to humans, differences and similarities of carboxylesterases between mice and human need to be elucidated. This review presents and discusses the research progress in structure and function of mouse and human carboxylesterases, and the role of these enzymes in lipid metabolism and metabolic disorders.

  10. Differential serotonergic innervation of the amygdala in bonobos and chimpanzees.

    Science.gov (United States)

    Stimpson, Cheryl D; Barger, Nicole; Taglialatela, Jared P; Gendron-Fitzpatrick, Annette; Hof, Patrick R; Hopkins, William D; Sherwood, Chet C

    2016-03-01

    Humans' closest living relatives are bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), yet these great ape species differ considerably from each other in terms of social behavior. Bonobos are more tolerant of conspecifics in competitive contexts and often use sexual behavior to mediate social interactions. Chimpanzees more frequently employ aggression during conflicts and actively patrol territories between communities. Regulation of emotional responses is facilitated by the amygdala, which also modulates social decision-making, memory and attention. Amygdala responsiveness is further regulated by the neurotransmitter serotonin. We hypothesized that the amygdala of bonobos and chimpanzees would differ in its neuroanatomical organization and serotonergic innervation. We measured volumes of regions and the length density of serotonin transporter-containing axons in the whole amygdala and its lateral, basal, accessory basal and central nuclei. Results showed that accessory basal nucleus volume was larger in chimpanzees than in bonobos. Of particular note, the amygdala of bonobos had more than twice the density of serotonergic axons than chimpanzees, with the most pronounced differences in the basal and central nuclei. These findings suggest that variation in serotonergic innervation of the amygdala may contribute to mediating the remarkable differences in social behavior exhibited by bonobos and chimpanzees. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. Object-based attention in chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Ushitani, Tomokazu; Imura, Tomoko; Tomonaga, Masaki

    2010-03-17

    We conducted three experiments to investigate how object-based components contribute to the attentional processes of chimpanzees and to examine how such processes operate with regard to perceptually structured objects. In Experiment 1, chimpanzees responded to a spatial cueing task that required them to touch a target appearing at either end of two parallel rectangles. We compared the time involved in shifting attention (cost of attentional shift) when the locations of targets were cued and non cued. Results showed that the cost of the attentional shift within one rectangle was smaller than that beyond the object's boundary, demonstrating object-based attention in chimpanzees. The results of Experiment 2, conducted with different stimulus configurations, replicated the results of Experiment 1, supporting that object-based attention operates in chimpanzees. In Experiment 3, the cost of attentional shift within a cued but partly occluded rectangle was shorter than that within a rectangle that was cued but divided in the middle. The results suggest that the attention of chimpanzees is activated not only by an explicit object but also by fragmented patches represented as an object at a higher-order perceptual level. Chimpanzees' object-based attention may be similar to that of humans. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

    Science.gov (United States)

    Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

    2018-03-01

    Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

  13. A neuroanatomical predictor of mirror self-recognition in chimpanzees.

    Science.gov (United States)

    Hecht, E E; Mahovetz, L M; Preuss, T M; Hopkins, W D

    2017-01-01

    The ability to recognize one's own reflection is shared by humans and only a few other species, including chimpanzees. However, this ability is highly variable across individual chimpanzees. In humans, self-recognition involves a distributed, right-lateralized network including frontal and parietal regions involved in the production and perception of action. The superior longitudinal fasciculus (SLF) is a system of white matter tracts linking these frontal and parietal regions. The current study measured mirror self-recognition (MSR) and SLF anatomy in 60 chimpanzees using diffusion tensor imaging. Successful self-recognition was associated with greater rightward asymmetry in the white matter of SLFII and SLFIII, and in SLFIII's gray matter terminations in Broca's area. We observed a visible progression of SLFIII's prefrontal extension in apes that show negative, ambiguous, and compelling evidence of MSR. Notably, SLFIII's terminations in Broca's area are not right-lateralized or particularly pronounced at the population level in chimpanzees, as they are in humans. Thus, chimpanzees with more human-like behavior show more human-like SLFIII connectivity. These results suggest that self-recognition may have co-emerged with adaptations to frontoparietal circuitry. © The Author (2016). Published by Oxford University Press.

  14. Emotional engagements predict and enhance social cognition in young chimpanzees.

    Science.gov (United States)

    Bard, Kim A; Bakeman, Roger; Boysen, Sarah T; Leavens, David A

    2014-09-01

    Social cognition in infancy is evident in coordinated triadic engagements, that is, infants attending jointly with social partners and objects. Current evolutionary theories of primate social cognition tend to highlight species differences in cognition based on human-unique cooperative motives. We consider a developmental model in which engagement experiences produce differential outcomes. We conducted a 10-year-long study in which two groups of laboratory-raised chimpanzee infants were given quantifiably different engagement experiences. Joint attention, cooperativeness, affect, and different levels of cognition were measured in 5- to 12-month-old chimpanzees, and compared to outcomes derived from a normative human database. We found that joint attention skills significantly improved across development for all infants, but by 12 months, the humans significantly surpassed the chimpanzees. We found that cooperativeness was stable in the humans, but by 12 months, the chimpanzee group given enriched engagement experiences significantly surpassed the humans. Past engagement experiences and concurrent affect were significant unique predictors of both joint attention and cooperativeness in 5- to 12-month-old chimpanzees. When engagement experiences and concurrent affect were statistically controlled, joint attention and cooperation were not associated. We explain differential social cognition outcomes in terms of the significant influences of previous engagement experiences and affect, in addition to cognition. Our study highlights developmental processes that underpin the emergence of social cognition in support of evolutionary continuity. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

  15. Cars kill chimpanzees: case report of a wild chimpanzee killed on a road at Bulindi, Uganda.

    Science.gov (United States)

    McLennan, Matthew R; Asiimwe, Caroline

    2016-07-01

    Roads have broadly adverse impacts on wildlife, including nonhuman primates. One direct effect is mortality from collisions with vehicles. While highly undesirable, roadkills provide valuable information on the health and condition of endangered species. We present a case report of a wild chimpanzee (Pan troglodytes schweinfurthii) killed crossing a road in Bulindi, Uganda, where chimpanzees inhabit forest fragments amid farmland. Details of the collision are constructed from eyewitness accounts of pedestrians. Physical examination of the cadaver indicated good overall body condition; at 40 kg, the deceased female was heavier than usual for an adult female East African chimpanzee. No external wounds or fractures were noted. Coprological assessment demonstrated infection by several gastrointestinal parasites commonly reported in living wild chimpanzees. Histopathology revealed eosinophilic enteritis and biliary hyperplasia potentially caused by parasite infection. However, eosinophilia was not widely spread into the submucosa, while egg/cyst counts suggested low-intensity parasite infections compared to healthy female chimpanzees of similar age in nearby Budongo Forest. No behavioral indicators of ill health were noted in the deceased female in the month prior to the accident. We conclude that cause of death was acute, i.e., shock from the collision, and was probably unrelated to parasite infection or any other underlying health condition. Notably, this female had asymmetrical polythelia, and, while nursing at the time of her death, had one functioning mammary gland only. In Uganda, where primates often inhabit human-dominated landscapes, human population growth and economic development has given rise to increasing motor traffic, while road development is enabling motorists to travel at greater speeds. Thus, the danger of roads to apes and other wildlife is rising, necessitating urgent strategies to reduce risks. Installation of simple speed-bumps-common on Ugandan

  16. Head-mounted eye tracking of a chimpanzee under naturalistic conditions.

    Directory of Open Access Journals (Sweden)

    Fumihiro Kano

    Full Text Available This study offers a new method for examining the bodily, manual, and eye movements of a chimpanzee at the micro-level. A female chimpanzee wore a lightweight head-mounted eye tracker (60 Hz on her head while engaging in daily interactions with the human experimenter. The eye tracker recorded her eye movements accurately while the chimpanzee freely moved her head, hands, and body. Three video cameras recorded the bodily and manual movements of the chimpanzee from multiple angles. We examined how the chimpanzee viewed the experimenter in this interactive setting and how the eye movements were related to the ongoing interactive contexts and actions. We prepared two experimentally defined contexts in each session: a face-to-face greeting phase upon the appearance of the experimenter in the experimental room, and a subsequent face-to-face task phase that included manual gestures and fruit rewards. Overall, the general viewing pattern of the chimpanzee, measured in terms of duration of individual fixations, length of individual saccades, and total viewing duration of the experimenter's face/body, was very similar to that observed in previous eye-tracking studies that used non-interactive situations, despite the differences in the experimental settings. However, the chimpanzee viewed the experimenter and the scene objects differently depending on the ongoing context and actions. The chimpanzee viewed the experimenter's face and body during the greeting phase, but viewed the experimenter's face and hands as well as the fruit reward during the task phase. These differences can be explained by the differential bodily/manual actions produced by the chimpanzee and the experimenter during each experimental phase (i.e., greeting gestures, task cueing. Additionally, the chimpanzee's viewing pattern varied depending on the identity of the experimenter (i.e., the chimpanzee's prior experience with the experimenter. These methods and results offer new

  17. How informative is the mouse for human gut microbiota research?

    Science.gov (United States)

    Nguyen, Thi Loan Anh; Vieira-Silva, Sara; Liston, Adrian; Raes, Jeroen

    2015-01-01

    The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research. © 2015. Published by The Company of Biologists Ltd.

  18. Social Attention in the Two Species of Pan: Bonobos Make More Eye Contact than Chimpanzees.

    Directory of Open Access Journals (Sweden)

    Fumihiro Kano

    Full Text Available Humans' two closest primate living relatives, bonobos and chimpanzees, differ behaviorally, cognitively, and emotionally in several ways despite their general similarities. While bonobos show more affiliative behaviors towards conspecifics, chimpanzees display more overt and severe aggression against conspecifics. From a cognitive standpoint, bonobos perform better in social coordination, gaze-following and food-related cooperation, while chimpanzees excel in tasks requiring extractive foraging skills. We hypothesized that attention and motivation play an important role in shaping the species differences in behavior, cognition, and emotion. Thus, we predicted that bonobos would pay more attention to the other individuals' face and eyes, as those are related to social affiliation and social coordination, while chimpanzees would pay more attention to the action target objects, as they are related to foraging. Using eye-tracking we examined the bonobos' and chimpanzees' spontaneous scanning of pictures that included eyes, mouth, face, genitals, and action target objects of conspecifics. Although bonobos and chimpanzees viewed those elements overall similarly, bonobos viewed the face and eyes longer than chimpanzees, whereas chimpanzees viewed the other elements, the mouth, action target objects and genitals, longer than bonobos. In a discriminant analysis, the individual variation in viewing patterns robustly predicted the species of individuals, thus clearly demonstrating species-specific viewing patterns. We suggest that such attentional and motivational differences between bonobos and chimpanzees could have partly contributed to shaping the species-specific behaviors, cognition, and emotion of these species, even in a relatively short period of evolutionary time.

  19. The emergence of social cognition in three young chimpanzees.

    Science.gov (United States)

    Tomasello, Michael; Carpenter, Malinda

    2005-01-01

    We report a series of 10 studies on the social-cognitive abilities of three young chimpanzees. The studies were all ones previously conducted with human infants. The chimpanzees were 1-5 years of age, had been raised mostly by humans, and were tested mostly directly by a familiar human experimenter. First, in a longitudinal investigation with repeated measurements from a social-cognitive test battery, the three young chimpanzees were similar in many ways to human infants; the major difference was a total lack of attempts to share attention with others either in joint attentional interactions or through declarative gestures. Second, in imitation-based tests of the understanding of intentional action, the chimpanzees, like human infants, showed an understanding of failed attempts and accidents; but they did not pay attention to the behavioral style of the actor or the actor's reasons for choosing a particular behavioral means. Third, in tests of their understanding of visual perception, the chimpanzees followed the gaze direction of a human to an out-of-sight location behind a barrier and gestured more to a human who could see them than to one who could not; but they showed no understanding that perceivers can focus their attention on one thing, or one aspect of a thing, within their perceptual fields for a reason. Finally, in tests of joint intentions and joint attention, the chimpanzees showed no ability to either reverse roles with a partner in a collaborative interaction or to set up a joint attentional framework for understanding the communicative intentions behind a pointing gesture. Taken together, these findings support the idea that the early ontogeny of human social cognition comprises two distinct trajectories, each with its own evolutionary history: one for understanding the basics of goal-directed action and perception, common to all apes, and another for sharing psychological states with others in collaborative acts involving joint intentions and

  20. Identification of chimpanzee leukocyte antigens (ChL-A) and their relation to HL-A

    NARCIS (Netherlands)

    Balner, H.

    1971-01-01

    The identification of a number of leukocyte antigens of chimpanzees is described. Suggestive evidence was obtained that some of the isoantisera recognize specificities of a hypothetical genetic system of chimpanzee antigens which, in analogy with the human HL-A system, is tentatively called ChL-A.

  1. Specific image characteristics influence attitudes about chimpanzee conservation and use as pets.

    Directory of Open Access Journals (Sweden)

    Stephen R Ross

    Full Text Available Chimpanzees are endangered in their native Africa but in the United States, they are housed not only in zoos and research centers but owned privately as pets and performers. In 2008, survey data revealed that the public is less likely to think that chimpanzees are endangered compared to other great apes, and that this is likely the result of media misportrayals in movies, television and advertisements. Here, we use an experimental survey paradigm with composite images of chimpanzees to determine the effects of specific image characteristics. We found that those viewing a photograph of a chimpanzee with a human standing nearby were 35.5% more likely to consider wild populations to be stable/healthy compared to those seeing the exact same picture without a human. Likewise, the presence of a human in the photograph increases the likelihood that they consider chimpanzees as appealing as a pet. We also found that respondents seeing images in which chimpanzees are shown in typically human settings (such as an office space were more likely to perceive wild populations as being stable and healthy compared to those seeing chimpanzees in other contexts. These findings shed light on the way that media portrayals of chimpanzees influence public attitudes about this important and endangered species.

  2. Specific image characteristics influence attitudes about chimpanzee conservation and use as pets.

    Science.gov (United States)

    Ross, Stephen R; Vreeman, Vivian M; Lonsdorf, Elizabeth V

    2011-01-01

    Chimpanzees are endangered in their native Africa but in the United States, they are housed not only in zoos and research centers but owned privately as pets and performers. In 2008, survey data revealed that the public is less likely to think that chimpanzees are endangered compared to other great apes, and that this is likely the result of media misportrayals in movies, television and advertisements. Here, we use an experimental survey paradigm with composite images of chimpanzees to determine the effects of specific image characteristics. We found that those viewing a photograph of a chimpanzee with a human standing nearby were 35.5% more likely to consider wild populations to be stable/healthy compared to those seeing the exact same picture without a human. Likewise, the presence of a human in the photograph increases the likelihood that they consider chimpanzees as appealing as a pet. We also found that respondents seeing images in which chimpanzees are shown in typically human settings (such as an office space) were more likely to perceive wild populations as being stable and healthy compared to those seeing chimpanzees in other contexts. These findings shed light on the way that media portrayals of chimpanzees influence public attitudes about this important and endangered species.

  3. How chimpanzees cooperate in a competitive world

    Science.gov (United States)

    Suchak, Malini; Eppley, Timothy M.; Campbell, Matthew W.; Feldman, Rebecca A.; Quarles, Luke F.; de Waal, Frans B. M.

    2016-01-01

    Our species is routinely depicted as unique in its ability to achieve cooperation, whereas our closest relative, the chimpanzee (Pan troglodytes), is often characterized as overly competitive. Human cooperation is assisted by the cost attached to competitive tendencies through enforcement mechanisms, such as punishment and partner choice. To examine if chimpanzees possess the same ability to mitigate competition, we set up a cooperative task in the presence of the entire group of 11 adults, which required two or three individuals to pull jointly to receive rewards. This open-group set-up provided ample opportunity for competition (e.g., freeloading, displacements) and aggression. Despite this unique set-up and initial competitiveness, cooperation prevailed in the end, being at least five times as common as competition. The chimpanzees performed 3,565 cooperative acts while using a variety of enforcement mechanisms to overcome competition and freeloading, as measured by (attempted) thefts of rewards. These mechanisms included direct protest by the target, third-party punishment in which dominant individuals intervened against freeloaders, and partner choice. There was a marked difference between freeloading and displacement; freeloading tended to elicit withdrawal and third-party interventions, whereas displacements were met with a higher rate of direct retaliation. Humans have shown similar responses in controlled experiments, suggesting shared mechanisms across the primates to mitigate competition for the sake of cooperation. PMID:27551075

  4. A dystrophic Duchenne mouse model for testing human antisense oligonucleotides.

    Directory of Open Access Journals (Sweden)

    Marcel Veltrop

    Full Text Available Duchenne muscular dystrophy (DMD is a severe muscle-wasting disease generally caused by reading frame disrupting mutations in the DMD gene resulting in loss of functional dystrophin protein. The reading frame can be restored by antisense oligonucleotide (AON-mediated exon skipping, allowing production of internally deleted, but partially functional dystrophin proteins as found in the less severe Becker muscular dystrophy. Due to genetic variation between species, mouse models with mutations in the murine genes are of limited use to test and further optimize human specific AONs in vivo. To address this we have generated the del52hDMD/mdx mouse. This model carries both murine and human DMD genes. However, mouse dystrophin expression is abolished due to a stop mutation in exon 23, while the expression of human dystrophin is abolished due to a deletion of exon 52. The del52hDMD/mdx model, like mdx, shows signs of muscle dystrophy on a histological level and phenotypically mild functional impairment. Local administration of human specific vivo morpholinos induces exon skipping and dystrophin restoration in these mice. Depending on the number of mismatches, occasional skipping of the murine Dmd gene, albeit at low levels, could be observed. Unlike previous models, the del52hDMD/mdx model enables the in vivo analysis of human specific AONs targeting exon 51 or exon 53 on RNA and protein level and muscle quality and function. Therefore, it will be a valuable tool for optimizing human specific AONs and genome editing approaches for DMD.

  5. Subplate in the developing cortex of mouse and human

    DEFF Research Database (Denmark)

    Wang, Wei Zhi; Hoerder-Suabedissen, Anna; Oeschger, Franziska M

    2010-01-01

    Abstract The subplate is a largely transient zone containing precocious neurons involved in several key steps of cortical development. The majority of subplate neurons form a compact layer in mouse, but are dispersed throughout a much larger zone in the human. In rodent, subplate neurons are among...... several genes that are specifically expressed in the subplate layer of the rodent dorsal cortex. Here we examined the human subplate for some of these markers. In the human dorsal cortex, connective tissue growth factor-positive neurons can be seen in the ventricular zone at 15-22 postconceptional weeks...... growth factor- and nuclear receptor-related 1-positive cells are two distinct cell populations of the human subplate. Furthermore, our microarray analysis in rodent suggested that subplate neurons produce plasma proteins. Here we demonstrate that the human subplate also expresses alpha2zinc...

  6. Arrhythmia phenotype in mouse models of human long QT.

    Science.gov (United States)

    Salama, Guy; Baker, Linda; Wolk, Robert; Barhanin, Jacques; London, Barry

    2009-03-01

    Enhanced dispersion of repolarization (DR) was proposed as a unifying mechanism, central to arrhythmia genesis in the long QT (LQT) syndrome. In mammalian hearts, K(+) channels are heterogeneously expressed across the ventricles resulting in 'intrinsic' DR that may worsen in long QT. DR was shown to be central to the arrhythmia phenotype of transgenic mice with LQT caused by loss of function of the dominant mouse K(+) currents. Here, we investigated the arrhythmia phenotype of mice with targeted deletions of KCNE1 and KCNH2 genes which encode for minK/IsK and Merg1 (mouse homolog of human ERG) proteins resulting in loss of function of I(Ks) and I(Kr), respectively. Both currents are important human K(+) currents associated with LQT5 and LQT2. Loss of minK, a protein subunit that interacts with KvLQT1, results in a marked reduction of I(Ks) giving rise to the Jervell and Lange-Nielsen syndrome and the reduced KCNH2 gene reduces MERG and I(Kr). Hearts were perfused, stained with di-4-ANEPPS and optically mapped to compare action potential durations (APDs) and arrhythmia phenotype in homozygous minK (minK(-/-)) and heterozygous Merg1 (Merg(+/-)) deletions and littermate control mice. MinK(-/-) mice has similar APDs and no arrhythmias (n = 4). Merg(+/-) mice had prolonged APDs (from 20 +/- 6 to 32 +/- 9 ms at the base, p mice (60% vs. 10%). A comparison of mouse models of LQT based on K(+) channel mutations important to human and mouse repolarization emphasizes DR as a major determinant of arrhythmia vulnerability.

  7. Human more complex than mouse at cellular level.

    Directory of Open Access Journals (Sweden)

    Alexander E Vinogradov

    Full Text Available The family of transcription factors with the C2H2 zinc finger domain is expanding in the evolution of vertebrates, reaching its highest numbers in the mammals. The question arises: whether an increased amount of these transcription factors is related to embryogenesis, nervous system, pathology or more of them are expressed in individual cells? Among mammals, the primates have a more complex anatomical structure than the rodents (e.g., brain. In this work, I show that a greater number of C2H2-ZF genes are expressed in the human cells than in the mouse cells. The effect is especially pronounced for C2H2-ZF genes accompanied with the KRAB domain. The relative difference between the numbers of C2H2-ZF(-KRAB genes in the human and mouse cellular transcriptomes even exceeds their difference in the genomes (i.e. a greater subset of existing in the genome genes is expressed in the human cellular transcriptomes compared to the mouse transcriptomes. The evolutionary turnover of C2H2-ZF(-KRAB genes acts in the direction of the revealed phenomenon, i.e. gene duplication and loss enhances the difference in the relative number of C2H2-ZF(-KRAB genes between human and mouse cellular transcriptomes. A higher amount of these genes is expressed in the brain and embryonic cells (compared with other tissues, whereas a lower amount--in the cancer cells. It is specifically the C2H2-ZF transcription factors whose repertoire is poorer in the cancer and richer in the brain (other transcription factors taken together do not show this trend. These facts suggest that increase of anatomical complexity is accompanied by a more complex intracellular regulation involving these transcription factors. Malignization is associated with simplification of this regulation. These results agree with the known fact that human cells are more resistant to oncogenic transformation than mouse cells. The list of C2H2-ZF genes whose suppression might be involved in malignization is provided.

  8. New Insights into the Evolution of the Human Diet from Faecal Biomarker Analysis in Wild Chimpanzee and Gorilla Faeces

    OpenAIRE

    Sistiaga, Ainara; Wrangham, Richard; Rothman, Jessica M.; Summons, Roger E.

    2015-01-01

    Our understanding of early human diets is based on reconstructed biomechanics of hominin jaws, bone and teeth isotopic data, tooth wear patterns, lithic, taphonomic and zooarchaeological data, which do not provide information about the relative amounts of different types of foods that contributed most to early human diets. Faecal biomarkers are proving to be a valuable tool in identifying relative proportions of plant and animal tissues in Palaeolithic diets. A limiting factor in the applicat...

  9. Human immune system mouse models of Ebola virus infection.

    Science.gov (United States)

    Spengler, Jessica R; Prescott, Joseph; Feldmann, Heinz; Spiropoulou, Christina F

    2017-08-01

    Human immune system (HIS) mice, immunodeficient mice engrafted with human cells (with or without donor-matched tissue), offer a unique opportunity to study pathogens that cause disease predominantly or exclusively in humans. Several HIS mouse models have recently been used to study Ebola virus (EBOV) infection and disease. The results of these studies are encouraging and support further development and use of these models in Ebola research. HIS mice provide a small animal model to study EBOV isolates, investigate early viral interactions with human immune cells, screen vaccines and therapeutics that modulate the immune system, and investigate sequelae in survivors. Here we review existing models, discuss their use in pathogenesis studies and therapeutic screening, and highlight considerations for study design and analysis. Finally, we point out caveats to current models, and recommend future efforts for modeling EBOV infection in HIS mice. Published by Elsevier B.V.

  10. Social Learning and Culture in Child and Chimpanzee.

    Science.gov (United States)

    Whiten, Andrew

    2017-01-03

    A few decades ago, we knew next to nothing about the behavior of our closest animal relative, the chimpanzee, but long-term field studies have since revealed an undreamed-of richness in the diversity of their cultural traditions across Africa. These discoveries have been complemented by a substantial suite of experimental studies, now bridging to the wild through field experiments. These field and experimental studies, particularly those in which direct chimpanzee-child comparisons have been made, delineate a growing set of commonalities between the phenomena of social learning and culture in the lives of chimpanzees and humans. These commonalities in social learning inform our understanding of the evolutionary roots of the cultural propensities the species share. At the same time, such comparisons throw into clearer relief the unique features of the distinctive human capacity for cumulative cultural evolution, and new research has begun to probe the key psychological attributes that may explain it.

  11. The truth about mouse, human, worms and yeast

    Directory of Open Access Journals (Sweden)

    Nelson David R

    2004-01-01

    Full Text Available Abstract Genome comparisons are behind the powerful new annotation methods being developed to find all human genes, as well as genes from other genomes. Genomes are now frequently being studied in pairs to provide cross-comparison datasets. This 'Noah's Ark' approach often reveals unsuspected genes and may support the deletion of false-positive predictions. Joining mouse and human as the cross-comparison dataset for the first two mammals are: two Drosophila species, D. melanogaster and D. pseudoobscura; two sea squirts, Ciona intestinalis and Ciona savignyi; four yeast (Saccharomyces species; two nematodes, Caenorhabditis elegans and Caenorhabditis briggsae; and two pufferfish (Takefugu rubripes and Tetraodon nigroviridis. Even genomes like yeast and C. elegans, which have been known for more than five years, are now being significantly improved. Methods developed for yeast or nematodes will now be applied to mouse and human, and soon to additional mammals such as rat and dog, to identify all the mammalian protein-coding genes. Current large disparities between human Unigene predictions (127,835 genes and gene-scanning methods (45,000 genes still need to be resolved. This will be the challenge during the next few years.

  12. Virus load in chimpanzees infected with human immunodeficiency virus type 1: effect of pre-exposure vaccination

    NARCIS (Netherlands)

    ten Haaft, P.; Cornelissen, M.; Goudsmit, J.; Koornstra, W.; Dubbes, R.; Niphuis, H.; Peeters, M.; Thiriart, C.; Bruck, C.; Heeney, J. L.

    1995-01-01

    Many reports indicate that a long-term asymptomatic state following human immunodeficiency virus type 1 (HIV-1) infection is associated with a low amount of circulating virus. To evaluate the possible effect of stabilizing a low virus load by non-sterilizing pre-exposure vaccination, a quantitative

  13. The Number of Cultural Traits Is Correlated with Female Group Size but Not with Male Group Size in Chimpanzee Communities

    OpenAIRE

    Lind, Johan; Lindenfors, Patrik

    2010-01-01

    What determines the number of cultural traits present in chimpanzee (Pan troglodytes) communities is poorly understood. In humans, theoretical models suggest that the frequency of cultural traits can be predicted by population size. In chimpanzees, however, females seem to have a particularly important role as cultural carriers. Female chimpanzees use tools more frequently than males. They also spend more time with their young, skewing the infants’ potential for social learning towards their ...

  14. Consolation in the aftermath of robberies resembles post-aggression consolation in chimpanzees

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz; Liebst, Lasse Suonperä; Bernasco, Wim

    2017-01-01

    Post-aggression consolation is assumed to occur in humans as well as in chimpanzees. While consolation following peer aggression has been observed in children, systematic evidence of consolation in human adults is rare. We used surveillance camera footage of the immediate aftermath of nonfatal...... to be consoled. Furthermore, we show that high levels of threat during the robbery increased the likelihood of receiving consolation afterwards. These patterns resemble post-aggression consolation in chimpanzees and suggest that emotions of empathic concern are involved in consolation across humans...... and chimpanzees....

  15. Inference of purifying and positive selection in three subspecies of chimpanzees (Pan troglodytes) from exome sequencing

    DEFF Research Database (Denmark)

    Bataillon, Thomas; Duan, Jinjie; Hvilsom, Christina

    2015-01-01

    of recent gene flow from Western into Eastern chimpanzees. The striking contrast in X-linked vs. autosomal polymorphism and divergence previously reported in Central chimpanzees is also found in Eastern and Western chimpanzees. We show that the direction of selection (DoS) statistic exhibits a strong non......-monotonic relationship with the strength of purifying selection S, making it inappropriate for estimating S. We instead use counts in synonymous vs. non-synonymous frequency classes to infer the distribution of S coefficients acting on non-synonymous mutations in each subspecies. The strength of purifying selection we...... infer is congruent with the differences in effective sizes of each subspecies: Central chimpanzees are undergoing the strongest purifying selection followed by Eastern and Western chimpanzees. Coding indels show stronger selection against indels changing the reading frame than observed in human...

  16. Usherin expression is highly conserved in mouse and human tissues.

    Science.gov (United States)

    Pearsall, Nicole; Bhattacharya, Gautam; Wisecarver, Jim; Adams, Joe; Cosgrove, Dominic; Kimberling, William

    2002-12-01

    Usher syndrome is an autosomal recessive disease that results in varying degrees of hearing loss and retinitis pigmentosa. Three types of Usher syndrome (I, II, and III) have been identified clinically with Usher type II being the most common of the three types. Usher type II has been localized to three different chromosomes 1q41, 3p, and 5q, corresponding to Usher type 2A, 2B, and 2C respectively. Usherin is a basement membrane protein encoded by the USH2A gene. Expression of usherin has been localized in the basement membrane of several tissues, however it is not ubiquitous. Immunohistochemistry detected usherin in the following human tissues: retina, cochlea, small and large intestine, pancreas, bladder, prostate, esophagus, trachea, thymus, salivary glands, placenta, ovary, fallopian tube, uterus, and testis. Usherin was absent in many other tissues such as heart, lung, liver, kidney, and brain. This distribution is consistent with the usherin distribution seen in the mouse. Conservation of usherin is also seen at the nucleotide and amino acid level when comparing the mouse and human gene sequences. Evolutionary conservation of usherin expression at the molecular level and in tissues unaffected by Usher 2a supports the important structural and functional role this protein plays in the human. In addition, we believe that these results could lead to a diagnostic procedure for the detection of Usher syndrome and those who carry an USH2A mutation.

  17. A critical role for the chimpanzee model in the study of hepatitis C.

    Science.gov (United States)

    Bukh, Jens

    2004-06-01

    Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV). Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees. Recent studies in chimpanzees have provided new insight into the nature of host immune responses-particularly the intrahepatic responses-following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. The RNA inoculated into chimpanzees originated from a single sequence, and the animals therefore had a monoclonal HCV infection. Monoclonal infection simplifies studies of HCV, because virus interaction with the host is not confounded by the quasispecies invariably present in a natural infection. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates. Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity.

  18. Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.

    Directory of Open Access Journals (Sweden)

    Anne Frentzen

    2011-04-01

    Full Text Available Hepatitis C virus (HCV is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.

  19. CYP1A1 and CYP1A2 expression: Comparing 'humanized' mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines

    International Nuclear Information System (INIS)

    Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji; Tateno, Chise; Makishima, Makoto; Yoshizato, Katsutoshi; Nebert, Daniel W.

    2009-01-01

    Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how 'human-like' can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1 C YP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carrying humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+) s evere-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs.

  20. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  1. Human tissue models in cancer research: looking beyond the mouse.

    Science.gov (United States)

    Jackson, Samuel J; Thomas, Gareth J

    2017-08-01

    Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

  2. A longitudinal assessment of vocabulary retention in symbol-competent chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Beran, Michael J; Heimbauer, Lisa A

    2015-01-01

    A number of studies from the 1960s to 1990s assessed the symbolic competence of great apes and other animals. These studies provided varying forms of evidence that some species were capable of symbolically representing their worlds, both through productive symbol use and comprehension of symbolic stimuli. One such project at the Language Research Center involved training chimpanzees (Pan troglodytes) to use lexigram symbols (geometric visual stimuli that represented objects, actions, locations, and individuals). Those studies now are more than 40 years old, and only a few of the apes involved in those studies are still alive. Three of these chimpanzees (and a fourth, control chimpanzee) were assessed across a 10-year period from 1999 to 2008 for their continued knowledge of lexigram symbols and, in the case of one chimpanzee, the continued ability to comprehend human speech. This article describes that longitudinal assessment and outlines the degree to which symbol competence was retained by these chimpanzees across that decade-long period. All chimpanzees showed retention of lexigram vocabularies, although there were differences in the number of words that were retained across the individuals. One chimpanzee also showed continual retention of human speech perception. These retained vocabularies largely consisted of food item names, but also names of inedible objects, locations, individuals, and some actions. Many of these retained words were for things that are not common in the daily lives of the chimpanzees and for things that are rarely requested by the chimpanzees. Thus, the early experiences of these chimpanzees in symbol-rich environments have produced long-lasting memories for symbol meaning, and those competencies have benefited research in a variety of topics in comparative cognition.

  3. The beginning of the end for chimpanzee experiments?

    Directory of Open Access Journals (Sweden)

    Knight Andrew

    2008-06-01

    chimpanzees, and other research fields presently deprived of funding, but would also increase the compliance of US animal researchers with internationally-accepted animal welfare and bioethical standards. It could even result in the first global moratorium on invasive research, for any non-human species, unless conducted in the best interests of the individual or species.

  4. Comprehension of functional support by enculturated chimpanzees Pan troglodytes

    Directory of Open Access Journals (Sweden)

    Anna M. YOCOM, Sarah T. BOYSEN

    2011-08-01

    conditions of enculturation, rich social interactions with humans and conspecifics, as well as active exploration of artifacts, materials, and other aspects of their physical environment had a significant impact on the animals’ ability to recognize the support relationships among the stimulus choices. Overall, the present findings provide strong support for the hypothesis that our chimpanzee subjects based their responses on an understanding of functional support which represented one facet of their folk physics repertoire [Current Zoology 57 (4: 429–440, 2011].

  5. The beginning of the end for chimpanzee experiments?

    Science.gov (United States)

    2008-01-01

    The advanced sensory, psychological and social abilities of chimpanzees confer upon them a profound ability to suffer when born into unnatural captive environments, or captured from the wild – as many older research chimpanzees once were – and when subsequently subjected to confinement, social disruption, and involuntary participation in potentially harmful biomedical research. Justifications for such research depend primarily on the important contributions advocates claim it has made toward medical advancements. However, a recent large-scale systematic review indicates that invasive chimpanzee experiments rarely provide benefits in excess of their profound animal welfare, bioethical and financial costs. The approval of large numbers of these experiments – particularly within the US – therefore indicates a failure of the ethics committee system. By 2008, legislative or policy bans or restrictions on invasive great ape experimentation existed in seven European countries, Japan, Australia and New Zealand. In continuing to conduct such experiments on chimpanzees and other great apes, the US was almost completely isolated internationally. In 2007, however, the US National Institutes of Health National Center for Research Resources implemented a permanent funding moratorium on chimpanzee breeding, which is expected to result in a major decline in laboratory chimpanzee numbers over the next 30 years, as most are retired or die. Additionally, in 2008, The Great Ape Protection Act was introduced to Congress. The bill proposed to end invasive research and testing on an estimated 1,200 chimpanzees confined within US laboratories, and, for approximately 600 federally-owned, to ensure their permanent retirement to sanctuaries. These events have created an unprecedented opportunity for US legislators, researchers, and others, to consider a global ban on invasive chimpanzee research. Such a ban would not only uphold the best interests of chimpanzees, and other research

  6. Identification of the porcine homologous of human disease causing trinucleotide repeat sequences

    DEFF Research Database (Denmark)

    Madsen, Lone Bruhn; Thomsen, Bo; Sølvsten, Christina Ane Elisabeth

    2007-01-01

    in this paper the identification of porcine noncoding and polyglutamine-encoding TNR regions and the comparison to the homologous TNRs from human, chimpanzee, dog, opossum, rat, and mouse. Several of the porcine TNR regions are highly polymorphic both within and between different breeds. The TNR regions...

  7. Genetic influences on receptive joint attention in chimpanzees (Pan troglodytes)

    DEFF Research Database (Denmark)

    Hopkins, William D; Keebaugh, Alaine C; Reamer, Lisa A

    2014-01-01

    Despite their genetic similarity to humans, our understanding of the role of genes on cognitive traits in chimpanzees remains virtually unexplored. Here, we examined the relationship between genetic variation in the arginine vasopressin V1a receptor gene (AVPR1A) and social cognition in chimpanzees...... cognition task was significantly heritable. Furthermore, males with one DupB(+) allele performed significantly better and were more responsive to socio-communicative cues than males homozygous for the DupB- deletion. Performance on a non-social cognition task was not associated with the AVPR1A genotype....... The collective findings show that AVPR1A polymorphisms are associated with individual differences in performance on a receptive joint attention task in chimpanzees....

  8. Distal Communication by Chimpanzees (Pan troglodytes): Evidence for Common Ground?

    Science.gov (United States)

    Leavens, David A; Reamer, Lisa A; Mareno, Mary Catherine; Russell, Jamie L; Wilson, Daniel; Schapiro, Steven J; Hopkins, William D

    2015-01-01

    van der Goot et al. (2014) proposed that distal, deictic communication indexed the appreciation of the psychological state of a common ground between a signaler and a receiver. In their study, great apes did not signal distally, which they construed as evidence for the human uniqueness of a sense of common ground. This study exposed 166 chimpanzees to food and an experimenter, at an angular displacement, to ask, "Do chimpanzees display distal communication?" Apes were categorized as (a) proximal or (b) distal signalers on each of four trials. The number of chimpanzees who communicated proximally did not statistically differ from the number who signaled distally. Therefore, contrary to the claim by van der Goot et al., apes do communicate distally. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

  9. Efficient search for a face by chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Tomonaga, Masaki; Imura, Tomoko

    2015-07-16

    The face is quite an important stimulus category for human and nonhuman primates in their social lives. Recent advances in comparative-cognitive research clearly indicate that chimpanzees and humans process faces in a special manner; that is, using holistic or configural processing. Both species exhibit the face-inversion effect in which the inverted presentation of a face deteriorates their perception and recognition. Furthermore, recent studies have shown that humans detect human faces among non-facial objects rapidly. We report that chimpanzees detected chimpanzee faces among non-facial objects quite efficiently. This efficient search was not limited to own-species faces. They also found human adult and baby faces--but not monkey faces--efficiently. Additional testing showed that a front-view face was more readily detected than a profile, suggesting the important role of eye-to-eye contact. Chimpanzees also detected a photograph of a banana as efficiently as a face, but a further examination clearly indicated that the banana was detected mainly due to a low-level feature (i.e., color). Efficient face detection was hampered by an inverted presentation, suggesting that configural processing of faces is a critical element of efficient face detection in both species. This conclusion was supported by a simple simulation experiment using the saliency model.

  10. Complete functional rescue of the ABCA1(-/-) mouse by human BAC transgenesis

    NARCIS (Netherlands)

    Coutinho, Jonathan M.; Singaraja, Roshni R.; Kang, Martin; Arenillas, David J.; Bertram, Lisa N.; Bissada, Nagat; Staels, Bart; Fruchart, Jean-Charles; Fievet, Catherine; Joseph-George, Ann M.; Wasserman, Wyeth W.; Hayden, Michael R.

    2005-01-01

    Humanized mouse models are useful tools to explore the functional and regulatory differences between human and murine orthologous genes. We have combined a bioinformatics approach and an in vivo approach to assess the functional and regulatory differences between the human and mouse ABCA1 genes.

  11. FANTOM5 CAGE profiles of human and mouse samples

    KAUST Repository

    Noguchi, Shuhei

    2017-08-29

    In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

  12. FANTOM5 CAGE profiles of human and mouse samples

    KAUST Repository

    Noguchi, Shuhei; Arakawa, Takahiro; Fukuda, Shiro; Furuno, Masaaki; Hasegawa, Akira; Hori, Fumi; Ishikawa-Kato, Sachi; Kaida, Kaoru; Kaiho, Ai; Kanamori-Katayama, Mutsumi; Kawashima, Tsugumi; Sakai, Mizuho; Simon, Christophe; Suzuki, Naoko; Tagami, Michihira; Watanabe, Shoko; Yoshida, Shigehiro; Arner, Peter; Axton, Richard A.; Babina, Magda; Baillie, J. Kenneth; Mummery, Christine L.; Barnett, Timothy C.; Beckhouse, Anthony G.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Carlisle, Ailsa J.; Clevers, Hans C.; Davis, Carrie A.; Nakachi, Yutaka; Detmar, Michael; Dohi, Taeko; Edge, Albert S.B.; Edinger, Matthias; Ehrlund, Anna; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Eslami, Afsaneh; Fagiolini, Michela; Nakahara, Fumio; Fairbairn, Lynsey; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Ferrai, Carmelo; Fisher, Malcolm E.; Forrester, Lesley M.; Fujita, Rie; Furusawa, Jun-ichi; Geijtenbeek, Teunis B.; Gingeras, Thomas; Nakamura, Toshiyuki; Goldowitz, Daniel; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J.; Hamaguchi, Masahide; Hara, Mitsuko; Hasegawa, Yuki; Herlyn, Meenhard; Heutink, Peter; Nakamura, Yukio; Hitchens, Kelly J.; Hume, David A.; Ikawa, Tomokatsu; Orlando, Valerio; Kai, Chieko; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Nozaki, Tadasuke; Khachigian, Levon M.; Kitamura, Toshio; Klein, Sarah; Klinken, S. Peter; Knox, Alan J.; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Lee, Weonju; Lennartsson, Andreas; Ogishima, Soichi; Mackay-sim, Alan; Mejhert, Niklas; Mizuno, Yosuke; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Morris, Kelly J.; Motohashi, Hozumi; Ohkura, Naganari; Ohno, Hiroshi; Ohshima, Mitsuhiro; Kojima, Miki; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Passier, Robert; Patrikakis, Margaret; Pombo, Ana; Pradhan-Bhatt, Swati; Qin, Xian-Yang; Rehli, Michael; Kubosaki, Atsutaka; Rizzu, Patrizia; Roy, Sugata; Sajantila, Antti; Sakaguchi, Shimon; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schmidl, Christian; Schneider, Claudio; Manabe, Ri-ichiroh; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sheng, Guojun; Shin, Jay W.; Sugiyama, Daisuke; Sugiyama, Takaaki; Summers, Kim M.; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Murata, Mitsuyoshi; Tatsukawa, Hideki; Tomoiu, Andru; Toyoda, Hiroo; van de Wetering, Marc; van den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Nagao-Sato, Sayaka; Yamaguchi, Yoko; Yamamoto, Masayuki; Yanagi-Mizuochi, Chiyo; Yoneda, Misako; Yonekura, Yohei; Zhang, Peter G.; Zucchelli, Silvia; Abugessaisa, Imad; Arner, Erik; Harshbarger, Jayson; Nakazato, Kenichi; Kondo, Atsushi; Lassmann, Timo; Lizio, Marina; Sahin, Serkan; Sengstag, Thierry; Severin, Jessica; Shimoji, Hisashi; Suzuki, Masanori; Suzuki, Harukazu; Kawai, Jun; Ninomiya, Noriko; Kondo, Naoto; Itoh, Masayoshi; Daub, Carsten O.; Kasukawa, Takeya; Kawaji, Hideya; Carninci, Piero; Forrest, Alistair R.R.; Hayashizaki, Yoshihide; Nishiyori-Sueki, Hiromi; Noma, Shohei; Saijyo, Eri; Saka, Akiko

    2017-01-01

    In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

  13. Gene expression and functional annotation of the human and mouse choroid plexus epithelium.

    Directory of Open Access Journals (Sweden)

    Sarah F Janssen

    Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE

  14. Stepwise development of MAIT cells in mouse and human.

    Directory of Open Access Journals (Sweden)

    Emmanuel Martin

    2009-03-01

    Full Text Available Mucosal-associated invariant T (MAIT cells display two evolutionarily conserved features: an invariant T cell receptor (TCRalpha (iTCRalpha chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC molecule, MHC-related molecule 1 (MR1. MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanValpha7.2 antibody and MAIT cell-specific iTCRalpha and TCRbeta transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRalpha and TCRbeta transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%-4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the

  15. Structural and molecular study of the supraspinatus muscle of modern humans (Homo sapiens) and common chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Potau, J M; Casado, A; de Diego, M; Ciurana, N; Arias-Martorell, J; Bello-Hellegouarch, G; Barbosa, M; de Paz, F J; Pastor, J F; Pérez-Pérez, A

    2018-04-21

    To analyze the muscle architecture and the expression pattern of the myosin heavy chain (MyHC) isoforms in the supraspinatus of Pan troglodytes and Homo sapiens in order to identify differences related to their different types of locomotion. We have analyzed nine supraspinatus muscles of Pan troglodytes and ten of Homo sapiens. For each sample, we have recorded the muscle fascicle length (MFL), the pennation angle, and the physiological cross-sectional area (PCSA). In the same samples, by real-time quantitative polymerase chain reaction, we have assessed the percentages of expression of the MyHC-I, MyHC-IIa, and MyHC-IIx isoforms. The mean MFL of the supraspinatus was longer (p = 0.001) and the PCSA was lower (p sapiens than in Pan troglodytes. Although the percentage of expression of MyHC-IIa was lower in Homo sapiens than in Pan troglodytes (p = 0.035), the combination of MyHC-IIa and MyHC-IIx was expressed at a similar percentage in the two species. The longer MFL in the human supraspinatus is associated with a faster contractile velocity, which reflects the primary function of the upper limbs in Homo sapiens-the precise manipulation of objects-an adaptation to bipedal locomotion. In contrast, the larger PCSA in Pan troglodytes is related to the important role of the supraspinatus in stabilizing the glenohumeral joint during the support phase of knuckle-walking. These functional differences of the supraspinatus in the two species are not reflected in differences in the expression of the MyHC isoforms. © 2018 Wiley Periodicals, Inc.

  16. Cognitive capacities for cooking in chimpanzees.

    Science.gov (United States)

    Warneken, Felix; Rosati, Alexandra G

    2015-06-22

    The transition to a cooked diet represents an important shift in human ecology and evolution. Cooking requires a set of sophisticated cognitive abilities, including causal reasoning, self-control and anticipatory planning. Do humans uniquely possess the cognitive capacities needed to cook food? We address whether one of humans' closest relatives, chimpanzees (Pan troglodytes), possess the domain-general cognitive skills needed to cook. Across nine studies, we show that chimpanzees: (i) prefer cooked foods; (ii) comprehend the transformation of raw food that occurs when cooking, and generalize this causal understanding to new contexts; (iii) will pay temporal costs to acquire cooked foods; (iv) are willing to actively give up possession of raw foods in order to transform them; and (v) can transport raw food as well as save their raw food in anticipation of future opportunities to cook. Together, our results indicate that several of the fundamental psychological abilities necessary to engage in cooking may have been shared with the last common ancestor of apes and humans, predating the control of fire. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  17. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

    Science.gov (United States)

    Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J

    2014-04-08

    Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.

  18. Prospective Memory in a Language-Trained Chimpanzee ("Pan Troglodytes")

    Science.gov (United States)

    Beran, Michael J.; Perdue, Bonnie M.; Bramlett, Jessica L.; Menzel, Charles R.; Evans, Theodore A.

    2012-01-01

    Prospective memory involves the encoding, retention, and implementation of an intended future action. Although humans show many forms of prospective memory, less is known about the future oriented processes of nonhuman animals, or their ability to use prospective memory. In this experiment, a chimpanzee named Panzee, who had learned to associate…

  19. Can Chimpanzees ("Pan troglodytes") Discriminate Appearance from Reality?

    Science.gov (United States)

    Krachun, Carla; Call, Josep; Tomasello, Michael

    2009-01-01

    A milestone in human development is coming to recognize that how something looks is not necessarily how it is. We tested appearance-reality understanding in chimpanzees ("Pan troglodytes") with a task requiring them to choose between a small grape and a big grape. The apparent relative size of the grapes was reversed using magnifying and…

  20. Efficient search for a face by chimpanzees (Pan troglodytes)

    OpenAIRE

    Tomonaga, Masaki; Imura, Tomoko

    2015-01-01

    The face is quite an important stimulus category for human and nonhuman primates in their social lives. Recent advances in comparative-cognitive research clearly indicate that chimpanzees and humans process faces in a special manner; that is, using holistic or configural processing. Both species exhibit the face-inversion effect in which the inverted presentation of a face deteriorates their perception and recognition. Furthermore, recent studies have shown that humans detect human faces amon...

  1. A comparison of some organizational characteristics of the mouse central retina and the human macula.

    Science.gov (United States)

    Volland, Stefanie; Esteve-Rudd, Julian; Hoo, Juyea; Yee, Claudine; Williams, David S

    2015-01-01

    Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

  2. Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

    Directory of Open Access Journals (Sweden)

    Pramod Nehete

    2014-01-01

    Full Text Available Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1β and anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γ by PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

  3. Chimpanzees and bonobos exhibit divergent spatial memory development.

    Science.gov (United States)

    Rosati, Alexandra G; Hare, Brian

    2012-11-01

    Spatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can illuminate which aspects of human spatial development are shared with other primates, versus which aspects are unique to our lineage. Here we present three studies examining spatial memory development in our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (P. paniscus). We first compared memory in a naturalistic foraging task where apes had to recall the location of resources hidden in a large outdoor enclosure with a variety of landmarks (Studies 1 and 2). We then compared older apes using a matched memory choice paradigm (Study 3). We found that chimpanzees exhibited more accurate spatial memory than bonobos across contexts, supporting predictions from these species' different feeding ecologies. Furthermore, chimpanzees - but not bonobos - showed developmental improvements in spatial memory, indicating that bonobos exhibit cognitive paedomorphism (delays in developmental timing) in their spatial abilities relative to chimpanzees. Together, these results indicate that the development of spatial memory may differ even between closely related species. Moreover, changes in the spatial domain can emerge during nonhuman ape ontogeny, much like some changes seen in human children. © 2012 Blackwell Publishing Ltd.

  4. Comparative histology of mouse, rat, and human pelvic ligaments.

    Science.gov (United States)

    Iwanaga, Ritsuko; Orlicky, David J; Arnett, Jameson; Guess, Marsha K; Hurt, K Joseph; Connell, Kathleen A

    2016-11-01

    The uterosacral (USL) and cardinal ligaments (CL) provide support to the uterus and pelvic organs, and the round ligaments (RL) maintain their position in the pelvis. In women with pelvic organ prolapse (POP), the connective tissue, smooth muscle, vasculature, and innervation of the pelvic support structures are altered. Rodents are commonly used animal models for POP research. However, the pelvic ligaments have not been defined in these animals. In this study, we hypothesized that the gross anatomy and histological composition of pelvic ligaments in rodents and humans are similar. We performed an extensive literature search for anatomical and histological descriptions of the pelvic support ligaments in rodents. We also performed anatomical dissections of the pelvis to define anatomical landmarks in relation to the ligaments. In addition, we identified the histological components of the pelvic ligaments and performed quantitative analysis of the smooth muscle bundles and connective tissue of the USL and RL. The anatomy of the USL, CL, and RL and their anatomical landmarks are similar in mice, rats, and humans. All species contain the same cellular components and have similar histological architecture. However, the cervical portion of the mouse USL and RL contain more smooth muscle and less connective tissue compared with rat and human ligaments. The pelvic support structures of rats and mice are anatomically and histologically similar to those of humans. We propose that both mice and rats are appropriate, cost-effective models for directed studies in POP research.

  5. Axial positrons emission tomography: from mouse to human brain imaging

    International Nuclear Information System (INIS)

    Brard, Emmanuel

    2013-01-01

    Positrons emission tomography is a nuclear imaging technics using nuclear decays. It is used both in clinical and preclinical studies. The later requires the use of small animals such as the mouse. The objective is to obtain the best signal with the best spatial resolution. Yet, a weight ratio between humans and mice indicates the need of a sub-millimeter resolution. A conventional scanner is based on detection modules surrounding the object to image and arranged perpendicularly. This implies a strong relationship between efficiency and spatial resolution. This work focuses on the axial geometry in which detection modules are arranged parallel to the object. This limits the relationship between the figures of merit, leading to both high spatial resolution and efficiency. The simulations of prototypes showed great perspectives in term of sub-millimeter resolution with efficiencies of 15 or 40% according to the scanner's axial extension. These results indicate great perspectives for both clinical and preclinical imaging. (author)

  6. Chimpanzee choice rates in competitive games match equilibrium game theory predictions.

    Science.gov (United States)

    Martin, Christopher Flynn; Bhui, Rahul; Bossaerts, Peter; Matsuzawa, Tetsuro; Camerer, Colin

    2014-06-05

    The capacity for strategic thinking about the payoff-relevant actions of conspecifics is not well understood across species. We use game theory to make predictions about choices and temporal dynamics in three abstract competitive situations with chimpanzee participants. Frequencies of chimpanzee choices are extremely close to equilibrium (accurate-guessing) predictions, and shift as payoffs change, just as equilibrium theory predicts. The chimpanzee choices are also closer to the equilibrium prediction, and more responsive to past history and payoff changes, than two samples of human choices from experiments in which humans were also initially uninformed about opponent payoffs and could not communicate verbally. The results are consistent with a tentative interpretation of game theory as explaining evolved behavior, with the additional hypothesis that chimpanzees may retain or practice a specialized capacity to adjust strategy choice during competition to perform at least as well as, or better than, humans have.

  7. Non-invasive body temperature measurement of wild chimpanzees using fecal temperature decline.

    Science.gov (United States)

    Jensen, Siv Aina; Mundry, Roger; Nunn, Charles L; Boesch, Christophe; Leendertz, Fabian H

    2009-04-01

    New methods are required to increase our understanding of pathologic processes in wild mammals. We developed a noninvasive field method to estimate the body temperature of wild living chimpanzees habituated to humans, based on statistically fitting temperature decline of feces after defecation. The method was established with the use of control measures of human rectal temperature and subsequent changes in fecal temperature over time. The method was then applied to temperature data collected from wild chimpanzee feces. In humans, we found good correspondence between the temperature estimated by the method and the actual rectal temperature that was measured (maximum deviation 0.22 C). The method was successfully applied and the average estimated temperature of the chimpanzees was 37.2 C. This simple-to-use field method reliably estimates the body temperature of wild chimpanzees and probably also other large mammals.

  8. Auditory ERPs to stimulus deviance in an awake chimpanzee (Pan troglodytes: towards hominid cognitive neurosciences.

    Directory of Open Access Journals (Sweden)

    Ari Ueno

    Full Text Available BACKGROUND: For decades, the chimpanzee, phylogenetically closest to humans, has been analyzed intensively in comparative cognitive studies. Other than the accumulation of behavioral data, the neural basis for cognitive processing in the chimpanzee remains to be clarified. To increase our knowledge on the evolutionary and neural basis of human cognition, comparative neurophysiological studies exploring endogenous neural activities in the awake state are needed. However, to date, such studies have rarely been reported in non-human hominid species, due to the practical difficulties in conducting non-invasive measurements on awake individuals. METHODOLOGY/PRINCIPAL FINDINGS: We measured auditory event-related potentials (ERPs of a fully awake chimpanzee, with reference to a well-documented component of human studies, namely mismatch negativity (MMN. In response to infrequent, deviant tones that were delivered in a uniform sound stream, a comparable ERP component could be detected as negative deflections in early latencies. CONCLUSIONS/SIGNIFICANCE: The present study reports the MMN-like component in a chimpanzee for the first time. In human studies, various ERP components, including MMN, are well-documented indicators of cognitive and neural processing. The results of the present study validate the use of non-invasive ERP measurements for studies on cognitive and neural processing in chimpanzees, and open the way for future studies comparing endogenous neural activities between humans and chimpanzees. This signifies an essential step in hominid cognitive neurosciences.

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

    Directory of Open Access Journals (Sweden)

    Kai Weng

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

  10. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

    Science.gov (United States)

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

    2017-06-01

    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  12. Diffusion of [2-14C]diazepam across hairless mouse skin and human skin

    International Nuclear Information System (INIS)

    Koch, R.L.; Palicharla, P.; Groves, M.J.

    1987-01-01

    The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. [ 14 C]Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14 C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber

  13. The extent of cultural variation between adjacent chimpanzee (Pan troglodytes verus) communities; a microecological approach.

    Science.gov (United States)

    Luncz, Lydia V; Boesch, Christophe

    2015-01-01

    Chimpanzees show cultural differences among populations across Africa but also between neighboring communities. The extent of these differences among neighbors, however, remains largely unknown. Comparing three neighboring chimpanzee community in the Taï National Park, Côte d'Ivoire, we found 27 putative cultural traits, including tool use, foraging, social interaction, communication and hunting behavior, exceeding by far previously known diversity. As foraging behavior is predominantly influenced by the environment, we further compared in detail ecological circumstances underlying insectivore feeding behavior to analyze whether foraging differences on Dorylus ants and Thoracotermes termites seen between neighboring chimpanzee communities were caused by environmental factors. Differences in the prey characteristics of Dorylus ants (aggression level, running speed, and nest structure) that could influence the behavior of chimpanzees were excluded, suggesting that the observed group-specific variation is not ecologically driven. Only one community preyed on Thoracotermes termites despite a similar abundance of termite mounds in all three territories, supporting the idea that this difference is also not shaped by the environment. Therefore, our study suggests that transmission of cultural knowledge plays a role in determining insectivory prey behavior. This behavioral plasticity, independent of ecological conditions, can lead to large numbers of cultural diversification between neighboring chimpanzee communities. These findings not only deepen our understanding of the cultural abilities of chimpanzees in the wild but also open up possible future comparisons of the origin of cultural diversification among humans and chimpanzees. © 2014 Wiley Periodicals, Inc.

  14. Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

    Science.gov (United States)

    Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

    2011-01-01

    Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

  15. Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice.

    Science.gov (United States)

    Zhao, Yue; Liu, Min; Chan, Xue Ying; Tan, Sue Yee; Subramaniam, Sharrada; Fan, Yong; Loh, Eva; Chang, Kenneth Tou En; Tan, Thiam Chye; Chen, Qingfeng

    2017-11-02

    Many immune parameters show circadian rhythms during the 24-hour day in mammals. The most striking circadian oscillation is the number of circulating immune cells that display an opposite rhythm between humans and mice. The physiological roles and mechanisms of circadian variations in mouse leukocytes are well studied, whereas for humans they remain unclear because of the lack of a proper model. In this study, we found that consistent with their natural host species, mouse and human circulating leukocytes exhibited opposite circadian oscillations in humanized mice. This cyclic pattern of trafficking correlated well with the diurnal expression levels of C-X-C chemokine receptor 4, which were controlled by the intracellular hypoxia-inducible factor 1α/aryl hydrocarbon receptor nuclear translocator-like heterodimer. Furthermore, we also discovered that p38 mitogen-activated protein kinases/mitogen-activated 2 had opposite effects between mice and humans in generating intracellular reactive oxygen species, which subsequently regulated HIF-1α expression. In conclusion, we propose humanized mice as a robust model for human circadian studies and reveal insights on a novel molecular clock network in the human circadian rhythm. © 2017 by The American Society of Hematology.

  16. Resistance of human and mouse myeloid leukemia cells to UV radiation

    International Nuclear Information System (INIS)

    Poljak-Blazi, M.; Osmak, M.; Hadzija, M.

    1989-01-01

    Sensitivity of mouse bone marrow and myeloid leukemia cells and sensitivity of human myeloid leukemia cells to UV light was tested. Criteria were the in vivo colony-forming ability of UV exposed cells and the inhibition of DNA synthesis during post-irradiation incubation for 24 h in vitro. Mouse bone marrow cells irradiated with a small dose of UV light (5 J/m 2 ) and injected into x-irradiated animals did not form hemopoietic colonies on recipient's spleens, and recipients died. However, mouse leukemia cells, after irradiation with higher doses of UV light, retained the ability to form colonies on the spleens, and all recipient mice died with typical symptoms of leukemia. In vitro, mouse bone marrow cells exhibited high sensitivity to UV light compared to mouse myeloid leukemia cells. Human leukemia cells were also resistant to UV light, but more sensitive than mouse leukemia cells. (author)

  17. Genetic subspecies diversity of the chimpanzee CD4 virus-receptor gene

    DEFF Research Database (Denmark)

    Hvilsom, Christina; Carlsen, Frands; Siegismund, Hans R

    2008-01-01

    six among the subspecies of chimpanzees. We found the CD4 receptor to be conserved in individuals belonging to the P. t. verus subspecies and divergent from the other three subspecies, which harbored highly variable CD4 receptors. The CD4 receptor of chimpanzees differed from that of humans. We...... question whether the observed diversity can explain the species-specific differences in susceptibility to and pathogenicity of SIV/HIV....

  18. Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus.

    Science.gov (United States)

    Drappier, Melissa; Opperdoes, Fred R; Michiels, Thomas

    2017-07-15

    Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. IMPORTANCE Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species Theilovirus includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L

  19. Growth and production kinetics of human x mouse and mouse hybridoma cells at reduced temperature and serum content.

    Science.gov (United States)

    Borth, N; Heider, R; Assadian, A; Katinger, H

    1992-09-01

    The growth and production kinetics of a mouse hybridoma cell line and a human-mouse heterohybridoma were analyzed under conditions of reduced temperature and serum content. The mouse hybridoma P24 had a constant cell specific production rate and RNA content, while the heterohybridoma 3D6-LC4 showed growth associated production kinetics and an increased RNA content at higher growth rates. This behaviour of 3D6-LC4 cells can be explained by the unusual cell cycle kinetics of this line, which can be arrested in any phase under growth limiting conditions, so that a low growth rate does not result in a greater portion of high producing G1-phase cells. Substrate limitation changes the cell cycle distribution of this cell line to a greater extent than low temperature or serum content, which indicates that this stress factor exerts a greater physiological control than assumed.

  20. Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products

    NARCIS (Netherlands)

    Rompelberg, C.J.M.; Ploemen, J.H.T.M.; Jespersen, S.; Greef, J. van der; Verhagen, H.; Bladeren, P.J. van

    1996-01-01

    The irreversible and reversible inhibition of glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and man. Using liver cytosol of human, rat and mouse, species differences were found in the rate of irreversible inhibition of GSTs by eugenol in the presence of the enzyme

  1. Development of a transgenic mouse model to study the immunogenicity of recombinant human insulin

    NARCIS (Netherlands)

    Torosantucci, Riccardo; Brinks, Vera; Kijanka, Grzegorz; Halim, Liem Andhyk; Sauerborn, Melody; Schellekens, Huub; Jiskoot, Wim

    2014-01-01

    Mouse models are commonly used to assess the immunogenicity of therapeutic proteins and to investigate the immunological processes leading to antidrug antibodies. The aim of this work was to develop a transgenic (TG) Balb/c mouse model for evaluating the immunogenicity of recombinant human insulin

  2. A phylogenomic study of human, dog, and mouse.

    Directory of Open Access Journals (Sweden)

    Gina Cannarozzi

    2007-01-01

    Full Text Available In recent years the phylogenetic relationship of mammalian orders has been addressed in a number of molecular studies. These analyses have frequently yielded inconsistent results with respect to some basal ordinal relationships. For example, the relative placement of primates, rodents, and carnivores has differed in various studies. Here, we attempt to resolve this phylogenetic problem by using data from completely sequenced nuclear genomes to base the analyses on the largest possible amount of data. To minimize the risk of reconstruction artifacts, the trees were reconstructed under different criteria-distance, parsimony, and likelihood. For the distance trees, distance metrics that measure independent phenomena (amino acid replacement, synonymous substitution, and gene reordering were used, as it is highly improbable that all of the trees would be affected the same way by any reconstruction artifact. In contradiction to the currently favored classification, our results based on full-genome analysis of the phylogenetic relationship between human, dog, and mouse yielded overwhelming support for a primate-carnivore clade with the exclusion of rodents.

  3. Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.

    Science.gov (United States)

    Hector, Ralph D; Dando, Owen; Landsberger, Nicoletta; Kilstrup-Nielsen, Charlotte; Kind, Peter C; Bailey, Mark E S; Cobb, Stuart R

    2016-01-01

    Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders.

  4. Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.

    Directory of Open Access Journals (Sweden)

    Ralph D Hector

    Full Text Available Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5 cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR, which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders.

  5. Update of the human and mouse Fanconi anemia genes.

    Science.gov (United States)

    Dong, Hongbin; Nebert, Daniel W; Bruford, Elspeth A; Thompson, David C; Joenje, Hans; Vasiliou, Vasilis

    2015-11-24

    Fanconi anemia (FA) is a recessively inherited disease manifesting developmental abnormalities, bone marrow failure, and increased risk of malignancies. Whereas FA has been studied for nearly 90 years, only in the last 20 years have increasing numbers of genes been implicated in the pathogenesis associated with this genetic disease. To date, 19 genes have been identified that encode Fanconi anemia complementation group proteins, all of which are named or aliased, using the root symbol "FANC." Fanconi anemia subtype (FANC) proteins function in a common DNA repair pathway called "the FA pathway," which is essential for maintaining genomic integrity. The various FANC mutant proteins contribute to distinct steps associated with FA pathogenesis. Herein, we provide a review update of the 19 human FANC and their mouse orthologs, an evolutionary perspective on the FANC genes, and the functional significance of the FA DNA repair pathway in association with clinical disorders. This is an example of a set of genes--known to exist in vertebrates, invertebrates, plants, and yeast--that are grouped together on the basis of shared biochemical and physiological functions, rather than evolutionary phylogeny, and have been named on this basis by the HUGO Gene Nomenclature Committee (HGNC).

  6. Serological cross-reactivity between Merkel cell polyomavirus and two closely related chimpanzee polyomaviruses.

    Directory of Open Access Journals (Sweden)

    Jérôme T J Nicol

    Full Text Available Phylogenetic analyses based on the major capsid protein sequence indicate that Merkel cell polyomavirus (MCPyV and chimpanzee polyomaviruses (PtvPyV1, PtvPyV2, and similarly Trichodysplasia spinulosa-associated polyomavirus (TSPyV and the orangutan polyomavirus (OraPyV1 are closely related. The existence of cross-reactivity between these polyomaviruses was therefore investigated. The findings indicated serological identity between the two chimpanzee polyomaviruses investigated and a high level of cross-reactivity with Merkel cell polyomavirus. In contrast, cross-reactivity was not observed between TSPyV and OraPyV1. Furthermore, specific antibodies to chimpanzee polyomaviruses were detected in chimpanzee sera by pre-incubation of sera with the different antigens, but not in human sera.

  7. The knowns and unknowns of chimpanzee culture

    OpenAIRE

    Gruber, Thibaud; Reynolds, Vernon; Zuberbühler, Klaus

    2014-01-01

    Claims of culture in chimpanzees appeared soon after the launch of the first field studies in africa.1 The notion of chimpanzee ‘material cultures’ was coined,2 and this was followed by a first formal comparison, which revealed an astonishing degree of behavioural diversity between the different study communities, mainly in terms of tool use.3 Although this behavioural diversity is still undisputed, the question of chimpanzee cultures has remained controversial.4–6 The debate has less to do w...

  8. Male yawning is more contagious than female yawning among chimpanzees (Pan troglodytes.

    Directory of Open Access Journals (Sweden)

    Jorg J M Massen

    Full Text Available Yawn contagion is not restricted to humans and has also been reported for several non-human animal species, including chimpanzees (Pan troglodytes. Contagious yawning may lead to synchronisation of behaviour. However, the function of contagious yawning is relatively understudied. In this study, we investigated the function of contagious yawning by focusing on two types of signal providers: close social associates and leaders. We provided a captive chimpanzee colony with videos of all individuals of their own group that were either yawning, or at rest. Consistent with other studies, we demonstrated that yawning is contagious for chimpanzees, yet we did not find any effect of relationship quality on yawn contagion. However, we show that yawn contagion is significantly higher when the video model is a yawning male than when the video model was a yawning female, and that this effect is most apparent among males. As males are dominant in chimpanzee societies, male signals may be more relevant to the rest of the group than female signals. Moreover, since chimpanzees form male-bonded societies, male signals are especially relevant for other males. Therefore, we suggest that the sex-differences of yawning contagion among chimpanzees reflect the function of yawning in the synchronisation of behaviour.

  9. Interactional synchrony in chimpanzees: Examination through a finger-tapping experiment.

    Science.gov (United States)

    Yu, Lira; Tomonaga, Masaki

    2015-05-11

    Humans often unconsciously coordinate behaviour with that of others in daily life. This interpersonal coordination, including mimicry and interactional synchrony, has been suggested to play a fundamental role in social interaction. If this coordinative behavior is socially adaptive, it may be shared with other highly social animal species. The current study targeted chimpanzees, which phylogenetically are the closest living relatives of humans and live in complex social groups, and examined whether interactional synchrony would emerge in pairs of chimpanzees when auditory information about a partner's movement was provided. A finger-tapping task was introduced via touch panels to elicit repetitive and rhythmic movement from each chimpanzee. We found that one of four chimpanzees produced significant changes in both tapping tempo and timing of the tapping relative to its partner's tap when auditory sounds were provided. Although the current results may have limitations in generalizing to chimpanzees as a species, we suggest that a finger-tapping task is one potential method to investigate interactional synchrony in chimpanzees under a laboratory setup.

  10. Using the mouse to model human disease: increasing validity and reproducibility

    Directory of Open Access Journals (Sweden)

    Monica J. Justice

    2016-02-01

    Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

  11. EPR detection of free radicals in UV-irradiated skin: mouse versus human

    International Nuclear Information System (INIS)

    Jurkiewicz, B.A.; Buettner, G.R.

    1996-01-01

    Ultraviolet radiation produces free radicals in Skh-1 mouse skin, contributing to photoaging and carcinogenesis. If a mouse model is a general indicator of free radical processes in human skin photobiology, then radical production observed in mouse and human skin should be directly comparative. In this work we show that UV radiation (λ > 300 nm, 14 μW/cm 2 UVB; 3.5 mW/cm 2 UVA) increases the ascorbate free radical (Asc) electron paramagnetic resonance (EPR) signal in both Skh-1 mouse skin (45%) and human facial skin biopsies (340%). Visible light (λ > 400 nm; 0.23 mW/cm 2 UVA) also increased the Ascsignal in human skin samples (45%) but did not increase baseline mouse Asc, indicating that human skin is more susceptible to free radical formation and that a chromophore for visible light may be present. Using EPR spin-trapping techniques, UV radiation produced spin adducts consistent with trapping lipid alkyl radicals in mouse skin (α-[4-pyridyl 1-oxide]-N-tert-butyl nitrone/alkyl radical adduct; a N = 15.56 G and a H 2.70 G) and lipid alkoxyl radicals in human skin (5,5-dimethylpyrroline -1-oxide/alkoxyl radical adduct; a N = 14.54 G and a H = 16.0 G). Topical application of the iron chelator Desferal to human skin significantly decreases these radicals (∼50%), indicating a role for iron in lipid peroxidation. (Author)

  12. PPARalpha/gamma expression and activity in mouse and human melanocytes and melanoma cells.

    Science.gov (United States)

    Eastham, Linda L; Mills, Caroline N; Niles, Richard M

    2008-06-01

    We examined the expression of PPARs and the effects of PPARalpha and PPARgamma agonists on growth of mouse and human melanocytes and melanoma cells. PPARalpha,beta, and PPARgamma mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARalpha mRNA levels were determined by QuantiGene assay. PPARalpha and PPARgamma protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter gene assay, while knockdown of PPARalpha expression was achieved by transient transfection of siRNA. Both mouse and human melanoma cells produced more PPARalpha and PPARgamma protein compared to melanocytes. PPARalpha mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPARalpha in human melanoma cells did not alter cell proliferation or morphology. PPARgamma-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPARalpha-selective agonists had limited effects. Increased expression of PPARalpha in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPARgamma agonists may be useful for arresting the growth of some melanomas.

  13. Conditional Expression of Human 15-Lipoxygenase-1 in Mouse Prostate Induces Prostatic Intraepithelial Neoplasia: The FLiMP Mouse Model

    Directory of Open Access Journals (Sweden)

    Uddhav P. Kelavkar

    2006-06-01

    Full Text Available The incidence and mortality of prostate cancer (PCa vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1, which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN, and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt, FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC, and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN. In summary, targeted overexpression of h

  14. Sex differences in wild chimpanzee behavior emerge during infancy.

    Directory of Open Access Journals (Sweden)

    Elizabeth V Lonsdorf

    Full Text Available The role of biological and social influences on sex differences in human child development is a persistent topic of discussion and debate. Given their many similarities to humans, chimpanzees are an important study species for understanding the biological and evolutionary roots of sex differences in human development. In this study, we present the most detailed analyses of wild chimpanzee infant development to date, encompassing data from 40 infants from the long-term study of chimpanzees at Gombe National Park, Tanzania. Our goal was to characterize age-related changes, from birth to five years of age, in the percent of observation time spent performing behaviors that represent important benchmarks in nutritional, motor, and social development, and to determine whether and in which behaviors sex differences occur. Sex differences were found for indicators of social behavior, motor development and spatial independence with males being more physically precocious and peaking in play earlier than females. These results demonstrate early sex differentiation that may reflect adult reproductive strategies. Our findings also resemble those found in humans, which suggests that biologically-based sex differences may have been present in the common ancestor and operated independently from the influences of modern sex-biased parental behavior and gender socialization.

  15. Age-related changes of MAO-A and -B distribution in human and mouse brain.

    Science.gov (United States)

    Mahy, N; Andrés, N; Andrade, C; Saura, J

    2000-01-01

    Age-related changes of MAO-A and -B were studied in human and BL/C57 mouse brain areas (substantia nigra, putamen and cerebellum). [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. MAO-A binding was higher in mouse, whereas MAO-B binding was higher in human. With aging, mouse MAO-A was significantly reduced between 4 and 8 weeks and remained unchanged until 19 months followed by a slight increase between 19 and 25 months. In contrast, no clear variation was observed in humans between the age of 17-93 years. In most of the structures studied a clear age-related increase in MAO-B was observed beginning in mouse brain at 4 weeks, whereas in human tissue this increase started at the age of 50-60 years. These results show marked differences in the levels and variations of mouse and human MAO-A and -B associated with aging and should be taken into account when extrapolating experimental data from mouse to human.

  16. Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes

    Science.gov (United States)

    Rowley, Jesse W.; Oler, Andrew J.; Tolley, Neal D.; Hunter, Benjamin N.; Low, Elizabeth N.; Nix, David A.; Yost, Christian C.; Zimmerman, Guy A.

    2011-01-01

    Inbred mice are a useful tool for studying the in vivo functions of platelets. Nonetheless, the mRNA signature of mouse platelets is not known. Here, we use paired-end next-generation RNA sequencing (RNA-seq) to characterize the polyadenylated transcriptomes of human and mouse platelets. We report that RNA-seq provides unprecedented resolution of mRNAs that are expressed across the entire human and mouse genomes. Transcript expression and abundance are often conserved between the 2 species. Several mRNAs, however, are differentially expressed in human and mouse platelets. Moreover, previously described functional disparities between mouse and human platelets are reflected in differences at the transcript level, including protease activated receptor-1, protease activated receptor-3, platelet activating factor receptor, and factor V. This suggests that RNA-seq is a useful tool for predicting differences in platelet function between mice and humans. Our next-generation sequencing analysis provides new insights into the human and murine platelet transcriptomes. The sequencing dataset will be useful in the design of mouse models of hemostasis and a catalyst for discovery of new functions of platelets. Access to the dataset is found in the “Introduction.” PMID:21596849

  17. Immunohistochemical Examination of Novel Rat Monoclonal Antibodies against Mouse and Human Podoplanin

    International Nuclear Information System (INIS)

    Kaji, Chiaki; Tsujimoto, Yuta; Kato Kaneko, Mika; Kato, Yukinari; Sawa, Yoshihiko

    2012-01-01

    This study aims to develop new monoclonal antibodies (mAbs) against mouse and human podoplanin. Rats were immunized with synthetic peptides, corresponding to amino acids 38–51 of mouse podoplanin or human podoplanin which is 100% homologous to the same site of monkey podoplanin; anti-mouse podoplanin mAb PMab-1 (IgG 2a ) and anti-human mAb NZ-1.2 (IgG 2a ) were established. In immunocytochemistry, the mouse melanoma B16-F10 and mouse podoplanin (mPDPN)-expressed CHO transfectant were stained by PMab-1; human lymphatic endothelial cells (LEC) and human podoplanin (hPDPN)-expressed squamous cell carcinoma HSC3 transfectant, were stained by NZ-1.2. Western-blot analysis detected an about 40-kDa protein in CHO-mPDPN and B16-F10 by PMab-1, and in HSC3-hPDPN and LEC by NZ-1.2. In frozen sections, PMab-1 reacted with mouse kidney, pulmonary alveoli, pulmonary pleura, and salivary gland myoepithelial cells while NZ-1.2 reacted to the human salivary gland myoepithelial cells. The immunostaining of paraffin-embedded sections also showed the reaction of PMab-1 or NZ-1.2 to the mouse or monkey kidney glomerulus, pulmonary alveoli, and lung lymphatic vessels. These results indicate that the two novel rat mAbs to the mouse and human/monkey podoplanin are useful for Western-blot and immunostaining of somatic tissues on paraffin-embedded sections as well as frozen sections

  18. Recombinant Chimpanzee Adenovirus Vaccine AdC7-M/E Protects against Zika Virus Infection and Testis Damage.

    Science.gov (United States)

    Xu, Kun; Song, Yufeng; Dai, Lianpan; Zhang, Yongli; Lu, Xuancheng; Xie, Yijia; Zhang, Hangjie; Cheng, Tao; Wang, Qihui; Huang, Qingrui; Bi, Yuhai; Liu, William J; Liu, Wenjun; Li, Xiangdong; Qin, Chuan; Shi, Yi; Yan, Jinghua; Zhou, Dongming; Gao, George F

    2018-03-15

    The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control. IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M

  19. Chimpanzees routinely fish for algae with tools during the dry season in Bakoun, Guinea.

    Science.gov (United States)

    Boesch, Christophe; Kalan, Ammie K; Agbor, Anthony; Arandjelovic, Mimi; Dieguez, Paula; Lapeyre, Vincent; Kühl, Hjalmar S

    2017-03-01

    Wild chimpanzees regularly use tools, made from sticks, leaves, or stone, to find flexible solutions to the ecological challenges of their environment. Nevertheless, some studies suggest strong limitations in the tool-using capabilities of chimpanzees. In this context, we present the discovery of a newly observed tool-use behavior in a population of chimpanzees (Pan troglodytes verus) living in the Bakoun Classified Forest, Guinea, where a temporary research site was established for 15 months. Bakoun chimpanzees of every age-sex class were observed to fish for freshwater green algae, Spirogrya sp., from rivers, streams, and ponds using long sticks and twigs, ranging from 9 cm up to 4.31 m in length. Using remote camera trap footage from 11 different algae fishing sites within an 85-km 2 study area, we found that algae fishing occurred frequently during the dry season and was non-existent during the rainy season. Chimpanzees were observed algae fishing for as little as 1 min to just over an hour, with an average duration of 9.09 min. We estimate that 364 g of Spirogyra algae could be retrieved in this time, based on human trials in the field. Only one other chimpanzee population living in Bossou, Guinea, has been described to customarily scoop algae from the surface of the water using primarily herbaceous tools. Here, we describe the new behavior found at Bakoun and compare it to the algae scooping observed in Bossou chimpanzees and the occasional variant reported in Odzala, Republic of the Congo. As these algae are reported to be high in protein, carbohydrates, and minerals, we hypothesize that chimpanzees are obtaining a nutritional benefit from this seasonally available resource. © 2016 Wiley Periodicals, Inc.

  20. Complex tasks force hand laterality and technological behaviour in naturalistically housed chimpanzees: inferences in hominin evolution.

    Science.gov (United States)

    Mosquera, M; Geribàs, N; Bargalló, A; Llorente, M; Riba, D

    2012-01-01

    Clear hand laterality patterns in humans are widely accepted. However, humans only elicit a significant hand laterality pattern when performing complementary role differentiation (CRD) tasks. Meanwhile, hand laterality in chimpanzees is weaker and controversial. Here we have reevaluated our results on hand laterality in chimpanzees housed in naturalistic environments at Fundació Mona (Spain) and Chimfunshi Wild Orphanage (Zambia). Our results show that the difference between hand laterality in humans and chimpanzees is not as great as once thought. Furthermore, we found a link between hand laterality and task complexity and also an even more interesting connection: CRD tasks elicited not only the hand laterality but also the use of tools. This paper aims to turn attention to the importance of this threefold connection in human evolution: the link between CRD tasks, hand laterality, and tool use, which has important evolutionary implications that may explain the development of complex behaviour in early hominins.

  1. Chimpanzees (Pan troglodytes) Produce the Same Types of 'Laugh Faces' when They Emit Laughter and when They Are Silent.

    Science.gov (United States)

    Davila-Ross, Marina; Jesus, Goncalo; Osborne, Jade; Bard, Kim A

    2015-01-01

    The ability to flexibly produce facial expressions and vocalizations has a strong impact on the way humans communicate, as it promotes more explicit and versatile forms of communication. Whereas facial expressions and vocalizations are unarguably closely linked in primates, the extent to which these expressions can be produced independently in nonhuman primates is unknown. The present work, thus, examined if chimpanzees produce the same types of facial expressions with and without accompanying vocalizations, as do humans. Forty-six chimpanzees (Pan troglodytes) were video-recorded during spontaneous play with conspecifics at the Chimfunshi Wildlife Orphanage. ChimpFACS was applied, a standardized coding system to measure chimpanzee facial movements, based on FACS developed for humans. Data showed that the chimpanzees produced the same 14 configurations of open-mouth faces when laugh sounds were present and when they were absent. Chimpanzees, thus, produce these facial expressions flexibly without being morphologically constrained by the accompanying vocalizations. Furthermore, the data indicated that the facial expression plus vocalization and the facial expression alone were used differently in social play, i.e., when in physical contact with the playmates and when matching the playmates' open-mouth faces. These findings provide empirical evidence that chimpanzees produce distinctive facial expressions independently from a vocalization, and that their multimodal use affects communicative meaning, important traits for a more explicit and versatile way of communication. As it is still uncertain how human laugh faces evolved, the ChimpFACS data were also used to empirically examine the evolutionary relation between open-mouth faces with laugh sounds of chimpanzees and laugh faces of humans. The ChimpFACS results revealed that laugh faces of humans must have gradually emerged from laughing open-mouth faces of ancestral apes. This work examines the main evolutionary

  2. From Immunodeficiency to Humanization: The Contribution of Mouse Models to Explore HTLV-1 Leukemogenesis

    Directory of Open Access Journals (Sweden)

    Eléonore Pérès

    2015-12-01

    Full Text Available The first discovered human retrovirus, Human T-Lymphotropic Virus type 1 (HTLV-1, is responsible for an aggressive form of T cell leukemia/lymphoma. Mouse models recapitulating the leukemogenesis process have been helpful for understanding the mechanisms underlying the pathogenesis of this retroviral-induced disease. This review will focus on the recent advances in the generation of immunodeficient and human hemato-lymphoid system mice with a particular emphasis on the development of mouse models for HTLV-1-mediated pathogenesis, their present limitations and the challenges yet to be addressed.

  3. Great ape origins of personality maturation and sex differences: a study of orangutans and chimpanzees.

    Science.gov (United States)

    Weiss, Alexander; King, James E

    2015-04-01

    Human personality development evinces increased emotional stability, prosocial tendencies, and responsibility. One hypothesis offered to explain this pattern is Social-Investment Theory, which posits that culturally defined social roles, including marriage and employment, are responsible for the increased maturity. Alternatively, Five-Factor Theory emphasizes the role of biological factors, such as those governing physical development, which may predate the emergence of humans. Five-Factor Theory, unlike Social-Investment Theory, predicts that all or some of the human personality developmental trends should be present in great apes, our closest evolutionary relatives. To test this prediction and to better understand the evolutionary origins of sex differences, we examined age and sex differences in the chimpanzee and orangutan personality domains Extraversion, Dominance, Neuroticism, and Agreeableness. We also examined the Activity and Gregariousness facets of Extraversion and the orangutan Intellect domain. Extraversion and Neuroticism declined across age groups in both species, in common with humans. A significant interaction indicated that Agreeableness declined in orangutans but increased in chimpanzees, as it does in humans, though this may reflect differences in how Agreeableness was defined in each species. Significant interactions indicated that male chimpanzees, unlike male orangutans, displayed higher Neuroticism scores than females and maintained higher levels of Activity and Dominance into old age than female chimpanzees, male orangutans, and female orangutans. Personality-age correlations were comparable across orangutans and chimpanzees and were similar to those reported in human studies. Sex differences were stronger in chimpanzees than in humans or orangutans. These findings support Five-Factor Theory, suggest the role of gene-culture coevolution in shaping personality development, and suggest that sex differences evolved independently in different

  4. Chimpanzee social intelligence: selfishness, altruism, and the mother-infant bond.

    Science.gov (United States)

    Hirata, Satoshi

    2009-01-01

    To better understand the human mind from an evolutionary perspective, a great deal of research has focused on the closest living relative of humans, the chimpanzee, using various approaches, including studies of social intelligence. Here, I review recent research related to several aspects of social intelligence, including deception, understanding of perception and intention, social learning, trading, cooperation, and regard for others. Many studies have demonstrated that chimpanzees are proficient in using their social intelligence for selfish motives to benefit from their interactions with others. In contrast, it is not yet clear whether chimpanzees engage in prosocial behaviors that benefit others; however, chimpanzee mother-infant interactions indicate the possibility of such behaviors. Therefore, I propose that chimpanzees possess rudimentary traits of human mental competence not only in terms of theory of mind in a broader sense but also in terms of prosociality involving regard for others. Mother-infant interactions appear to be particularly important to understanding the manifestation of social intelligence from an evolutionary perspective.

  5. Aping expressions? Chimpanzees produce distinct laugh types when responding to laughter of others.

    Science.gov (United States)

    Davila-Ross, Marina; Allcock, Bethan; Thomas, Chris; Bard, Kim A

    2011-10-01

    Humans have the ability to replicate the emotional expressions of others even when they undergo different emotions. Such distinct responses of expressions, especially positive expressions, play a central role in everyday social communication of humans and may give the responding individuals important advantages in cooperation and communication. The present work examined laughter in chimpanzees to test whether nonhuman primates also use their expressions in such distinct ways. The approach was first to examine the form and occurrence of laugh replications (laughter after the laughter of others) and spontaneous laughter of chimpanzees during social play and then to test whether their laugh replications represented laugh-elicited laugh responses (laughter triggered by the laughter of others) by using a quantitative method designed to measure responses in natural social settings. The results of this study indicated that chimpanzees produce laugh-elicited laughter that is distinct in form and occurrence from their spontaneous laughter. These findings provide the first empirical evidence that nonhuman primates have the ability to replicate the expressions of others by producing expressions that differ in their underlying emotions and social implications. The data further showed that the laugh-elicited laugh responses of the subjects were closely linked to play maintenance, suggesting that chimpanzees might gain important cooperative and communicative advantages by responding with laughter to the laughter of their social partners. Notably, some chimpanzee groups of this study responded more with laughter than others, an outcome that provides empirical support of a socialization of expressions in great apes similar to that of humans.

  6. The number of cultural traits is correlated with female group size but not with male group size in chimpanzee communities.

    Directory of Open Access Journals (Sweden)

    Johan Lind

    Full Text Available What determines the number of cultural traits present in chimpanzee (Pan troglodytes communities is poorly understood. In humans, theoretical models suggest that the frequency of cultural traits can be predicted by population size. In chimpanzees, however, females seem to have a particularly important role as cultural carriers. Female chimpanzees use tools more frequently than males. They also spend more time with their young, skewing the infants' potential for social learning towards their mothers. In Gombe, termite fishing has been shown to be transmitted from mother to offspring. Lastly, it is female chimpanzees that transfer between communities and thus have the possibility of bringing in novel cultural traits from other communities. From these observations we predicted that females are more important cultural carriers than males. Here we show that the reported number of cultural traits in chimpanzee communities correlates with the number of females in chimpanzee communities, but not with the number of males. Hence, our results suggest that females are the carriers of chimpanzee culture.

  7. The number of cultural traits is correlated with female group size but not with male group size in chimpanzee communities.

    Science.gov (United States)

    Lind, Johan; Lindenfors, Patrik

    2010-03-24

    What determines the number of cultural traits present in chimpanzee (Pan troglodytes) communities is poorly understood. In humans, theoretical models suggest that the frequency of cultural traits can be predicted by population size. In chimpanzees, however, females seem to have a particularly important role as cultural carriers. Female chimpanzees use tools more frequently than males. They also spend more time with their young, skewing the infants' potential for social learning towards their mothers. In Gombe, termite fishing has been shown to be transmitted from mother to offspring. Lastly, it is female chimpanzees that transfer between communities and thus have the possibility of bringing in novel cultural traits from other communities. From these observations we predicted that females are more important cultural carriers than males. Here we show that the reported number of cultural traits in chimpanzee communities correlates with the number of females in chimpanzee communities, but not with the number of males. Hence, our results suggest that females are the carriers of chimpanzee culture.

  8. Human and mouse mononuclear phagocyte networks: a tale of two species?

    Directory of Open Access Journals (Sweden)

    Gary eReynolds

    2015-06-01

    Full Text Available Dendritic cells (DCs, monocytes and macrophages are a heterogeneous population of mononuclear phagocytes that are involved in antigen processing and presentation to initiate and regulate immune responses to pathogens, vaccines, tumour and tolerance to self. In addition to their afferent sentinel function, DCs and macrophages are also critical as effectors and coordinators of inflammation and homeostasis in peripheral tissues. Harnessing DCs and macrophages for therapeutic purposes has major implications for infectious disease, vaccination, transplantation, tolerance induction, inflammation and cancer immunotherapy. There has been a paradigm shift in our understanding of the developmental origin and function of the cellular constituents of the mononuclear phagocyte system. Significant progress has been made in tandem in both human and mouse mononuclear phagocyte biology. This progress has been accelerated by comparative biology analysis between mouse and human, which has proved to be an exceptionally fruitful strategy to harmonise findings across species. Such analyses have provided unexpected insights and facilitated productive reciprocal and iterative processes to inform our understanding of human and mouse mononuclear phagocytes. In this review, we discuss the strategies, power and utility of comparative biology approaches to integrate recent advances in human and mouse mononuclear phagocyte biology and its potential to drive forward clinical translation of this knowledge. We also present a functional framework on the parallel organisation of human and mouse mononuclear phagocyte networks.

  9. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    Directory of Open Access Journals (Sweden)

    Ivanna Ihnatovych

    Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  10. The importance of witnessed agency in chimpanzee social learning of tool use.

    Science.gov (United States)

    Hopper, Lydia M; Lambeth, Susan P; Schapiro, Steven J; Whiten, Andrew

    2015-03-01

    Social learning refers to individuals learning from others, including information gained through indirect social influences, such as the results of others' actions and changes in the physical environment. One method to determine the relative influence of these varieties of information is the 'ghost display', in which no model is involved, but subjects can watch the results that a model would produce. Previous research has shown mixed success by chimpanzees (Pan troglodytes) learning from ghost displays, with some studies suggesting learning only in relatively simple tasks. To explore whether the failure of chimpanzees to learn from a ghost display may be due to neophobia when tested singly or a requirement for more detailed information for complex tasks, we presented ghost displays of a tool-use task to chimpanzees in their home social groups. Previous tests have revealed that chimpanzees are unable to easily solve this tool-use task asocially, or learn from ghost displays when tested singly, but can learn after observing conspecifics in a group setting. In the present study, despite being tested in a group situation, chimpanzees still showed no success in solving the task via trial-and-error learning, in a baseline condition, nor in learning the task from the ghost display. Simply being in the presence of their group mates and being shown the affordances of the task was not sufficient to encourage learning. Following this, in an escalating series of tests, we examined the chimpanzees' ability to learn from a demonstration by models with agency: (1) a human; (2) video footage of a chimpanzee; (3) a live chimpanzee model. In the first two of these 'social' conditions, subjects showed limited success. By the end of the final open diffusion phase, which was run to determine whether this new behavior would be transmitted among the group after seeing a successful chimpanzee use the task, 83% of chimpanzees were now successful. This confirmed a marked overall effect of

  11. Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

    Directory of Open Access Journals (Sweden)

    Felicia Leccia

    2016-07-01

    Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

  12. Transmission of multiple traditions within and between chimpanzee groups.

    Science.gov (United States)

    Whiten, Andrew; Spiteri, Antoine; Horner, Victoria; Bonnie, Kristin E; Lambeth, Susan P; Schapiro, Steven J; de Waal, Frans B M

    2007-06-19

    Field reports provide increasing evidence for local behavioral traditions among fish, birds, and mammals. These findings are significant for evolutionary biology because social learning affords faster adaptation than genetic change and has generated new (cultural) forms of evolution. Orangutan and chimpanzee field studies suggest that like humans, these apes are distinctive among animals in each exhibiting over 30 local traditions. However, direct evidence is lacking in apes and, with the exception of vocal dialects, in animals generally for the intergroup transmission that would allow innovations to spread widely and become evolutionarily significant phenomena. Here, we provide robust experimental evidence that alternative foraging techniques seeded in different groups of chimpanzees spread differentially not only within groups but serially across two further groups with substantial fidelity. Combining these results with those from recent social-diffusion studies in two larger groups offers the first experimental evidence that a nonhuman species can sustain unique local cultures, each constituted by multiple traditions. The convergence of these results with those from the wild implies a richness in chimpanzees' capacity for culture, a richness that parsimony suggests was shared with our common ancestor.

  13. Evaluation of perfluoroalkyl acid activity using primary mouse and human hepatocytes

    International Nuclear Information System (INIS)

    Rosen, Mitchell B.; Das, Kaberi P.; Wood, Carmen R.; Wolf, Cynthia J.; Abbott, Barbara D.; Lau, Christopher

    2013-01-01

    While perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been studied at length, less is known about the biological activity of other perfluoroalkyl acids (PFAAs) detected in the environment. Using a transient transfection assay developed in COS-1 cells, our group has previously evaluated a variety of PFAAs for activity associated with activation of peroxisome proliferator-activated receptor alpha (PPARα). Here we use primary heptatocytes to further assess the biological activity of a similar group of PFAAs using custom designed Taqman Low Density Arrays. Primary mouse and human hepatoyctes were cultured for 48 h in the presence of varying concentrations of 12 different PFAAs or Wy14,643, a known activator of PPARα. Total RNA was collected and the expression of 48 mouse or human genes evaluated. Gene selection was based on either in-house liver microarray data (mouse) or published data using primary hepatocytes (human). Gene expression in primary mouse hepatocytes was more restricted than expected. Genes typically regulated in whole tissue by PPARα agonists were not altered in mouse cells including Acox1, Me1, Acaa1a, Hmgcs1, and Slc27a1. Cyp2b10, a gene regulated by the constitutive androstane receptor and a transcript normally up-regulated by in vivo exposure to PFAAs, was also unchanged in cultured mouse hepatocytes. Cyp4a14, Ehhadh, Pdk4, Cpt1b, and Fabp1 were regulated as expected in mouse cells. A larger group of genes were differentially expressed in human primary hepatocytes, however, little consistency was observed across compounds with respect to which genes produced a significant dose response making the determination of relative biological activity difficult. This likely reflects weaker activation of PPARα in human versus rodent cells as well as variation among individual cell donors. Unlike mouse cells, CYP2B6 was up-regulated in human hepatocytes by a number of PFAAs as was PPARδ. Rankings were conducted on the limited

  14. Sex Differences in Object Manipulation in Wild Immature Chimpanzees (Pan troglodytes schweinfurthii) and Bonobos (Pan paniscus): Preparation for Tool Use?

    Science.gov (United States)

    Koops, Kathelijne; Furuichi, Takeshi; Hashimoto, Chie; van Schaik, Carel P

    2015-01-01

    Sex differences in immatures predict behavioural differences in adulthood in many mammal species. Because most studies have focused on sex differences in social interactions, little is known about possible sex differences in 'preparation' for adult life with regards to tool use skills. We investigated sex and age differences in object manipulation in immature apes. Chimpanzees use a variety of tools across numerous contexts, whereas bonobos use few tools and none in foraging. In both species, a female bias in adult tool use has been reported. We studied object manipulation in immature chimpanzees at Kalinzu (Uganda) and bonobos at Wamba (Democratic Republic of Congo). We tested predictions of the 'preparation for tool use' hypothesis. We confirmed that chimpanzees showed higher rates and more diverse types of object manipulation than bonobos. Against expectation, male chimpanzees showed higher object manipulation rates than females, whereas in bonobos no sex difference was found. However, object manipulation by male chimpanzees was play-dominated, whereas manipulation types of female chimpanzees were more diverse (e.g., bite, break, carry). Manipulation by young immatures of both species was similarly dominated by play, but only in chimpanzees did it become more diverse with age. Moreover, in chimpanzees, object types became more tool-like (i.e., sticks) with age, further suggesting preparation for tool use in adulthood. The male bias in object manipulation in immature chimpanzees, along with the late onset of tool-like object manipulation, indicates that not all (early) object manipulation (i.e., object play) in immatures prepares for subsistence tool use. Instead, given the similarity with gender differences in human children, object play may also function in motor skill practice for male-specific behaviours (e.g., dominance displays). In conclusion, even though immature behaviours almost certainly reflect preparation for adult roles, more detailed future work is

  15. Sex Differences in Object Manipulation in Wild Immature Chimpanzees (Pan troglodytes schweinfurthii and Bonobos (Pan paniscus: Preparation for Tool Use?

    Directory of Open Access Journals (Sweden)

    Kathelijne Koops

    Full Text Available Sex differences in immatures predict behavioural differences in adulthood in many mammal species. Because most studies have focused on sex differences in social interactions, little is known about possible sex differences in 'preparation' for adult life with regards to tool use skills. We investigated sex and age differences in object manipulation in immature apes. Chimpanzees use a variety of tools across numerous contexts, whereas bonobos use few tools and none in foraging. In both species, a female bias in adult tool use has been reported. We studied object manipulation in immature chimpanzees at Kalinzu (Uganda and bonobos at Wamba (Democratic Republic of Congo. We tested predictions of the 'preparation for tool use' hypothesis. We confirmed that chimpanzees showed higher rates and more diverse types of object manipulation than bonobos. Against expectation, male chimpanzees showed higher object manipulation rates than females, whereas in bonobos no sex difference was found. However, object manipulation by male chimpanzees was play-dominated, whereas manipulation types of female chimpanzees were more diverse (e.g., bite, break, carry. Manipulation by young immatures of both species was similarly dominated by play, but only in chimpanzees did it become more diverse with age. Moreover, in chimpanzees, object types became more tool-like (i.e., sticks with age, further suggesting preparation for tool use in adulthood. The male bias in object manipulation in immature chimpanzees, along with the late onset of tool-like object manipulation, indicates that not all (early object manipulation (i.e., object play in immatures prepares for subsistence tool use. Instead, given the similarity with gender differences in human children, object play may also function in motor skill practice for male-specific behaviours (e.g., dominance displays. In conclusion, even though immature behaviours almost certainly reflect preparation for adult roles, more detailed

  16. A Functional Assay for Putative Mouse and Human Definitive Endoderm using Chick Whole-Embryo Cultures

    DEFF Research Database (Denmark)

    Johannesson, Martina; Semb, Tor Henrik; Serup, Palle

    2012-01-01

    . Thus, the purpose of this study is to describe a method whereby the in vivo functionality of DE derived from ESCs can be assessed. Methods: By directed differentiation, putative DE was derived from human and mouse ESCs. This putative DE was subsequently transplanted into the endoderm of chick embryos...... to determine any occurrence of integration. Putative DE was analyzed by gene and protein expression prior to transplantation and 48 h post transplantation. Results: Putative DE, derived from mouse and human ESCs, was successfully integrated within the chick endoderm. Endoderm-specific genes were expressed...... result show that putative DE integrates with the chick endoderm and participate in the development of the chicken gut, indicating the generation of functional DE from ESCs. This functional assay can be used to assess the generation of functional DE derived from both human and mouse ESCs and provides...

  17. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human.

    Science.gov (United States)

    MacRae, Sheila L; Zhang, Quanwei; Lemetre, Christophe; Seim, Inge; Calder, Robert B; Hoeijmakers, Jan; Suh, Yousin; Gladyshev, Vadim N; Seluanov, Andrei; Gorbunova, Vera; Vijg, Jan; Zhang, Zhengdong D

    2015-04-01

    Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  18. The price of play: self-organized infant mortality cycles in chimpanzees.

    Directory of Open Access Journals (Sweden)

    Hjalmar S Kuehl

    Full Text Available Chimpanzees have been used extensively as a model system for laboratory research on infectious diseases. Ironically, we know next to nothing about disease dynamics in wild chimpanzee populations. Here, we analyze long-term demographic and behavioral data from two habituated chimpanzee communities in Taï National Park, Côte d'Ivoire, where previous work has shown respiratory pathogens to be an important source of infant mortality. In this paper we trace the effect of social connectivity on infant mortality dynamics. We focus on social play which, as the primary context of contact between young chimpanzees, may serve as a key venue for pathogen transmission. Infant abundance and mortality rates at Taï cycled regularly and in a way that was not well explained in terms of environmental forcing. Rather, infant mortality cycles appeared to self-organize in response to the ontogeny of social play. Each cycle started when the death of multiple infants in an outbreak synchronized the reproductive cycles of their mothers. A pulse of births predictably arrived about twelve months later, with social connectivity increasing over the following two years as the large birth cohort approached the peak of social play. The high social connectivity at this play peak then appeared to facilitate further outbreaks. Our results provide the first evidence that social play has a strong role in determining chimpanzee disease transmission risk and the first record of chimpanzee disease cycles similar to those seen in human children. They also lend more support to the view that infectious diseases are a major threat to the survival of remaining chimpanzee populations.

  19. Causal knowledge and imitation/emulation switching in chimpanzees (Pan troglodytes) and children (Homo sapiens).

    Science.gov (United States)

    Horner, Victoria; Whiten, Andrew

    2005-07-01

    This study explored whether the tendency of chimpanzees and children to use emulation or imitation to solve a tool-using task was a response to the availability of causal information. Young wild-born chimpanzees from an African sanctuary and 3- to 4-year-old children observed a human demonstrator use a tool to retrieve a reward from a puzzle-box. The demonstration involved both causally relevant and irrelevant actions, and the box was presented in each of two conditions: opaque and clear. In the opaque condition, causal information about the effect of the tool inside the box was not available, and hence it was impossible to differentiate between the relevant and irrelevant parts of the demonstration. However, in the clear condition causal information was available, and subjects could potentially determine which actions were necessary. When chimpanzees were presented with the opaque box, they reproduced both the relevant and irrelevant actions, thus imitating the overall structure of the task. When the box was presented in the clear condition they instead ignored the irrelevant actions in favour of a more efficient, emulative technique. These results suggest that emulation is the favoured strategy of chimpanzees when sufficient causal information is available. However, if such information is not available, chimpanzees are prone to employ a more comprehensive copy of an observed action. In contrast to the chimpanzees, children employed imitation to solve the task in both conditions, at the expense of efficiency. We suggest that the difference in performance of chimpanzees and children may be due to a greater susceptibility of children to cultural conventions, perhaps combined with a differential focus on the results, actions and goals of the demonstrator.

  20. Epitope mapping of functional domains of human factor V with human and mouse monoclonal antibodies

    International Nuclear Information System (INIS)

    Annamalai, A.E.; Rao, A.K.; Chiu, H.C.; Wang, D.; Dutta-Roy, A.K.; Colman, R.W.

    1986-01-01

    The authors previously described two human monoclonal antibodies (MAbs) which inactivated factor V. The authors have now purified the predominant antibody (H2) on protein A Sepharose using a pH gradient and typed it as IgG 1 ,. Immunoprecipitation of 125 I-human factor Va with H2 demonstrated specificity for the heavy chain (D), Mr = 105,000. The authors compared using ELISA the competitive binding to factor Va, of H2, H1 and two mouse MAbs, B38 (directed to E) and B10 (to activation peptide, Cl). All four antibodies recognized distinct epitopes in factor V with steric overlap in some cases. Factor Xa showed a concentration dependent competition for binding of H1, H2 and B38 but not B10 to factor V/Va in ELISA. All MAbs bound to factor V/Va in the absence of Ca ++ . However, Ca ++ at 8 mM increased the binding of H1 and H2 to 165% and 360% and did not have any effect on the binding of either mouse MAbs. Prothrombin at a concentration of up to 400 μg/ml did not inhibit binding of any of these antibodies. Thus, both the light (E) and heavy (D) chains of factor Va but not the activation peptide (Cl) interact with factor Xa as defined by the MAbs. In addition, sites on both chains for Ca ++ are recognized by particular MAbs (H1 and H2). These studies increase their knowledge of the interactions of factor V domains in the formation of prothrombinase complex

  1. Consolation in the aftermath of robberies resembles post-aggression consolation in chimpanzees

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz; Liebst, Lasse Suonperä; Bernasco, Wim

    2017-01-01

    Post-aggression consolation is assumed to occur in humans as well as in chimpanzees. While consolation following peer aggression has been observed in children, systematic evidence of consolation in human adults is rare. We used surveillance camera footage of the immediate aftermath of nonfatal...

  2. Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

    Science.gov (United States)

    Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

    2017-12-01

    With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

  3. Automated whole-genome multiple alignment of rat, mouse, and human

    Energy Technology Data Exchange (ETDEWEB)

    Brudno, Michael; Poliakov, Alexander; Salamov, Asaf; Cooper, Gregory M.; Sidow, Arend; Rubin, Edward M.; Solovyev, Victor; Batzoglou, Serafim; Dubchak, Inna

    2004-07-04

    We have built a whole genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline which combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment, and consists of two main steps: (1) alignment of the mouse and rat genomes; and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human and 97% of all alignments with human sequence > 100kb agree with a three-way synteny map built independently using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment; and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.

  4. Localization and regulation of mouse pantothenate kinase 2 [The PanK2 Genes of Mouse and Human Specify Proteins with Distinct Subcellular Locations

    Energy Technology Data Exchange (ETDEWEB)

    Leonardi, Roberta [St. Jude Children' s Research Hospital, Memphis, TN (United States); Zhang, Yong-Mei [St. Jude Children' s Research Hospital, Memphis, TN (United States); Lykidis, Athanasios [DOE Joint Genome Inst., Walnut Creek, CA (United States); Rock, Charles O. [St. Jude Children' s Research Hospital, Memphis, TN (United States); Jackowski, Suzanne [St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2007-09-07

    Coenzyme A (CoA) biosynthesis is initiated by pantothenatekinase (PanK) and CoA levels are controlled through differentialexpression and feedback regulation of PanK isoforms. PanK2 is amitochondrial protein in humans, but comparative genomics revealed thatacquisition of a mitochondrial targeting signal was limited to primates.Human and mouse PanK2 possessed similar biochemical properties, withinhibition by acetylCoA and activation by palmitoylcarnitine. Mouse PanK2localized in the cytosol, and the expression of PanK2 was higher in humanbrain compared to mouse brain. Differences in expression and subcellularlocalization should be considered in developing a mouse model for humanPanK2 deficiency.

  5. Deadly Respiratory Disease in Wild Chimpanzees

    Centers for Disease Control (CDC) Podcasts

    Dr. Tony Goldberg, Professor of Epidemiology at the School of Veterinary Medicine and Associate Director for Research at the University of Wisconsin, Madison, Global Health Institute, discusses an outbreak of rhinovirus C in chimpanzees in Uganda.

  6. Chimpanzee culture extends beyond matrilineal family units.

    Science.gov (United States)

    van Leeuwen, Edwin J C; Mundry, Roger; Cronin, Katherine A; Bodamer, Mark; Haun, Daniel B M

    2017-06-19

    The 'grooming handclasp' is one of the most well-established cultural traditions in chimpanzees. A recent study by Wrangham et al.[1] reduced the cultural scope of grooming-handclasp behavior by showing that grooming-handclasp style convergence is "explained by matrilineal relationship rather than conformity" [1]. Given that we previously reported cultural differences in grooming-handclasp style preferences in captive chimpanzees [2], we tested the alternative view posed by Wrangham et al.[1] in the chimpanzee populations that our original results were based on. Using the same outcome variable as Wrangham et al.[1] - the proportion of high-arm grooming featuring palm-to-palm clasping - we found that matrilineal relationships explained neither within-group homogeneity nor between-group heterogeneity, thereby corroborating our original conclusion that grooming-handclasp behavior can represent a group-level cultural tradition in chimpanzees. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Toshisada Nishida (1941–2011: Chimpanzee Rapport.

    Directory of Open Access Journals (Sweden)

    Frans B. M. de Waal

    2011-10-01

    Full Text Available Frans de Waal pays tribute to pioneering primatologist Toshisada Nishida, who transformed our understanding of chimpanzee behavior and culture and galvanized efforts to ensure their conservation.

  8. Structural organization of the human and mouse laminin beta2 chain genes, and alternative splicing at the 5' end of the human transcript

    DEFF Research Database (Denmark)

    Durkin, M E; Gautam, M; Loechel, F

    1996-01-01

    We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon-intron organ......We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon...

  9. Carbonic anhydrases and their functional differences in human and mouse sperm physiology.

    Science.gov (United States)

    José, O; Torres-Rodríguez, P; Forero-Quintero, L S; Chávez, J C; De la Vega-Beltrán, J L; Carta, F; Supuran, C T; Deitmer, J W; Treviño, C L

    2015-12-25

    Fertilization is a key reproductive event in which sperm and egg fuse to generate a new individual. Proper regulation of certain parameters (such as intracellular pH) is crucial for this process. Carbonic anhydrases (CAs) are among the molecular entities that control intracellular pH dynamics in most cells. Unfortunately, little is known about the function of CAs in mammalian sperm physiology. For this reason, we re-explored the expression of CAI, II, IV and XIII in human and mouse sperm. We also measured the level of CA activity, determined by mass spectrometry, and found that it is similar in non-capacitated and capacitated mouse sperm. Importantly, we found that CAII activity accounts for half of the total CA activity in capacitated mouse sperm. Using the general CA inhibitor ethoxyzolamide, we studied how CAs participate in fundamental sperm physiological processes such as motility and acrosome reaction in both species. We found that capacitated human sperm depend strongly on CA activity to support normal motility, while capacitated mouse sperm do not. Finally, we found that CA inhibition increases the acrosome reaction in capacitated human sperm, but not in capacitated mouse sperm. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

    Directory of Open Access Journals (Sweden)

    Laura A. Runck

    2014-04-01

    Full Text Available Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations

  11. Stable nitrogen isotope analysis of dentine serial sections elucidate sex differences in weaning patterns of wild chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Fahy, Geraldine E; Richards, Michael P; Fuller, Benjamin T; Deschner, Tobias; Hublin, Jean-Jacques; Boesch, Christophe

    2014-04-01

    Offspring provisioning is one of the most energetically demanding aspects of reproduction for female mammals. Variation in lactation length and weaning strategies between chimpanzees (Pan troglodytes), our closest living relative, and modern human societies have been reported. When and why these changes occurred is frequently debated. Our study used stable nitrogen isotope data of tooth root dentine from wild Western chimpanzees (Pan troglodytes verus) in Taï National Park, Côte d'Ivoire, to quantify weaning in these chimpanzees and explore if infant sex plays a role in maternal investment. We analyzed serial sections of deciduous lateral incisor root dentine from four Taï chimpanzees to establish the δ(15) N signal of nursing infants; we then analyzed serial sections of first permanent mandibular molar root dentine from 12 Taï chimpanzees to provide quantitative δ(15) N data on weaning in this population. Up to 2 years of age both sexes exhibited dentine δ(15) N values ≈2-3‰ higher than adult female Taï chimpanzees, consistent with a nursing signal. Thereafter a steady decrease in δ(15) N values consistent with the onset, and progression, of weaning, was visible. Sex differences were also evident, where male δ(15) N values decreased at a significantly slower rate compared to females. Confirmation of sex differences in maternal investment among Taï chimpanzees, demonstrates the viability of using isotope analysis to investigate weaning in non-human primates. Additionally, assuming that behaviors observed in the Taï chimpanzees are illustrative of the ancestral pattern, our results provide a platform to enable the trajectory of weaning in human evolution to be further explored. Copyright © 2013 Wiley Periodicals, Inc.

  12. Introduction of the human proα1(I) collagen gene into proα1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen

    International Nuclear Information System (INIS)

    Schnieke, A.; Dziadek, M.; Bateman, J.; Mascara, T.; Harbers, K.; Gelinas, R.; Jaenisch, R.

    1987-01-01

    The Mov-13 mouse strain carries a retroviral insertion in the proα1(I) collagen gene that prevents transcription of the gene. Cell lines derived from homozygous embryos do not express type I collagen although normal amounts of proα2 mRNA are synthesized. The authors have introduced genomic clones of either the human or mouse proα1(I) collagen gene into homozygous cell lines to assess whether the human or mouse proα1(I) chains can associate with the endogenous mouse proα2(I) chain to form stable type I collagen. The human gene under control of the simian virus 40 promoter was efficiently transcribed in the transfected cells. Protein analyses revealed that stable heterotrimers consisting of two human α1 chains and one mouse α2 chain were formed and that type I collagen was secreted by the transfected cells at normal rates. However, the electrophoretic migration of both α1(I) and α2(I) chains in the human-mouse hybrid molecules were retarded, compared to the α(I) chains in control mouse cells. Inhibition of the posttranslational hydroxylation of lysine and proline resulted in comigration of human and mouse α1 and α2 chains, suggesting that increased posttranslational modification caused the altered electrophoretic migration in the human-mouse hybrid molecules. Amino acid sequence differences between the mouse and human α chains may interfere with the normal rate of helix formation and increase the degree of posttranslational modifications similar to those observed in patients with lethal perinatal osteogenesis imperfecta. The Mov-13 mouse system should allow the authors to study the effect specific mutations introduced in transfected proα1(I) genes have on the synthesis, assembly, and function of collagen I

  13. Stereotypical Behaviors in Chimpanzees Rescued from the African Bushmeat and Pet Trade

    Directory of Open Access Journals (Sweden)

    Ashlynn Dube

    2012-12-01

    Full Text Available Many orphaned chimpanzees whose mothers are illegally killed for their meat (bushmeat in Africa are sold as pets or kept caged at hotels and businesses to attract tourists. As a result of being separated from their mothers and other chimpanzees at an early age, and spending years in impoverished captive conditions, some of these individuals engage in abnormal behaviors, including stereotypically scratching at their flesh and repetitively rocking back and forth. This paper presents case studies of Poco and Safari, two chimpanzees who were rescued by sanctuaries after living alone on display for humans at businesses for the first 7 to 8 years of their lives. Decades after their rescue, they still engage in stereotypical behaviors as a result of the psychological and physical trauma they endured early on. This paper combines data from in depth interviews with caregivers and direct observations of abnormal behaviors to assess psychological distress in captive-living chimpanzees. Our results highlight some lesser known harms of the bushmeat trade and the detrimental life-long consequences that keeping chimpanzees as “pets” can have on their mental health.

  14. Stable isotope evidence of meat eating and hunting specialization in adult male chimpanzees

    Science.gov (United States)

    Fahy, Geraldine E.; Richards, Michael; Riedel, Julia; Hublin, Jean-Jacques; Boesch, Christophe

    2013-01-01

    Observations of hunting and meat eating in our closest living relatives, chimpanzees (Pan troglodytes), suggest that among primates, regular inclusion of meat in the diet is not a characteristic unique to Homo. Wild chimpanzees are known to consume vertebrate meat, but its actual dietary contribution is, depending on the study population, often either unknown or minimal. Constraints on continual direct observation throughout the entire hunting season mean that behavioral observations are limited in their ability to accurately quantify meat consumption. Here we present direct stable isotope evidence supporting behavioral observations of frequent meat eating among wild adult male chimpanzees (Pan troglodytes verus) in Taï National Park, Côte d’Ivoire. Meat eating among some of the male chimpanzees is significant enough to result in a marked isotope signal detectable on a short-term basis in their hair keratin and long-term in their bone collagen. Although both adult males and females and juveniles derive their dietary protein largely from daily fruit and seasonal nut consumption, our data indicate that some adult males also derive a large amount of dietary protein from hunted meat. Our results reinforce behavioral observations of male-dominated hunting and meat eating in adult Taï chimpanzees, suggesting that sex differences in food acquisition and consumption may have persisted throughout hominin evolution, rather than being a recent development in the human lineage. PMID:23530185

  15. Phylogenetic analyses of behavior support existence of culture among wild chimpanzees.

    Science.gov (United States)

    Lycett, Stephen J; Collard, Mark; McGrew, William C

    2007-11-06

    Culture has long been considered to be not only unique to humans, but also responsible for making us qualitatively different from all other forms of life. In recent years, however, researchers studying chimpanzees (Pan troglodytes) have challenged this idea. Natural populations of chimpanzees have been found to vary greatly in their behavior. Because many of these interpopulation differences cannot be readily explained by ecological factors, it has been argued that they result from social learning and, therefore, can be regarded as cultural variations. Recent studies showing social transmission in captive chimpanzee populations suggest that this hypothesis is plausible. However, the culture hypothesis has been questioned on the grounds that the behavioral variation may be explained at a proximate level by genetic differences between subspecies. Here we use cladistic analyses of the major cross-site behavioral data set to test the hypothesis that the behavioral differences among the best-documented chimpanzee populations are genetically determined. If behavioral diversity is primarily the product of genetic differences between subspecies, then population data should show less phylogenetic structure when data from a single subspecies (P. t. schweinfurthii) are compared with data from two subspecies (P. t. verus and P. t. schweinfurthii) analyzed together. Our findings are inconsistent with the hypothesis that the observed behavioral patterns of wild chimpanzee populations can be explained primarily by genetic differences between subspecies. Instead, our results support the suggestion that the behavioral patterns are the product of social learning and, therefore, can be considered cultural.

  16. Integration of mouse and human genome-wide association data identifies KCNIP4 as an asthma gene

    NARCIS (Netherlands)

    Himes, Blanca E.; Sheppard, Keith; Berndt, Annerose; Leme, Adriana S.; Myers, Rachel A.; Gignoux, Christopher R.; Levin, Albert M.; Gauderman, W. James; Yang, James J.; Mathias, Rasika A.; Romieu, Isabelle; Torgerson, Dara G.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Klanderman, Barbara; Ziniti, John; Senter-Sylvia, Jody; Szefler, Stanley J.; Lemanske, Robert F.; Zeiger, Robert S.; Strunk, Robert C.; Martinez, Fernando D.; Boushey, Homer; Chinchilli, Vernon M.; Israel, Elliot; Mauger, David; Koppelman, Gerard H.; Postma, Dirkje S.; Nieuwenhuis, Maartje A. E.; Vonk, Judith M.; Lima, John J.; Irvin, Charles G.; Peters, Stephen P.; Kubo, Michiaki; Tamari, Mayumi; Nakamura, Yusuke; Litonjua, Augusto A.; Tantisira, Kelan G.; Raby, Benjamin A.; Bleecker, Eugene R.; Meyers, Deborah A.; London, Stephanie J.; Barnes, Kathleen C.; Gilliland, Frank D.; Williams, L. Keoki; Burchard, Esteban G.; Nicolae, Dan L.; Ober, Carole; DeMeo, Dawn L.; Silverman, Edwin K.; Paigen, Beverly; Churchill, Gary; Shapiro, Steve D.; Weiss, Scott

    2013-01-01

    Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR). The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify

  17. Toxicity testing of human assisted reproduction devices using the mouse embryo assay.

    NARCIS (Netherlands)

    Punt-Van der Zalm, J.P.; Hendriks, J.C.M.; Westphal, J.R.; Kremer, J.A.M.; Teerenstra, S.; Wetzels, A.M.M.

    2009-01-01

    Systems to assess the toxicity of materials used in human assisted reproduction currently lack efficiency and/or sufficient discriminatory power. The development of 1-cell CBA/B6 F1 hybrid mouse embryos to blastocysts, expressed as blastocyst rate (BR), is used to measure toxicity. The embryos were

  18. Partial functional complementation between human and mouse cytomegalovirus chemokine receptor homologues

    DEFF Research Database (Denmark)

    Farrell, Helen E; Abraham, Alexander M; Cardin, Rhonda D

    2011-01-01

    The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33-m...

  19. Global similarity and local divergence in human and mouse gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-09-01

    Full Text Available Abstract Background A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction ( Conclusion The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection.

  20. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

    NARCIS (Netherlands)

    S.L. Macrae (Sheila L.); Q. Zhang (Quanwei); C. Lemetre (Christophe); I. Seim (Inge); R.B. Calder (Robert B.); J.H.J. Hoeijmakers (Jan); Y. Suh (Yousin); V.N. Gladyshev (Vadim N.); A. Seluanov (Andrei); V. Gorbunova (Vera); J. Vijg (Jan); Z.D. Zhang (Zhengdong D.)

    2015-01-01

    textabstractGenome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM

  1. The toxicity of silver and silica nanoparticles in comparable human and mouse cell lines

    DEFF Research Database (Denmark)

    Foldbjerg, Rasmus; Beer, Christiane; Sutherland, Duncan S

    The toxicity of silica (SiO2) and PVP-coated silver (Ag) nanoparticles (NPs) was investigated in two pairs of human or mouse cell lines originating from lung epithelium (A549 and ASB-XIV) and macrophages (THP-1 and J744A.1). Both NPs were characterized in H2O and cell media and demonstrated to be...

  2. 4,300-year-old chimpanzee sites and the origins of percussive stone technology.

    Science.gov (United States)

    Mercader, Julio; Barton, Huw; Gillespie, Jason; Harris, Jack; Kuhn, Steven; Tyler, Robert; Boesch, Christophe

    2007-02-27

    Archaeological research in the African rainforest reveals unexpected results in the search for the origins of hominoid technology. The ancient Panin sites from Côte d'Ivoire constitute the only evidence of prehistoric ape behavior known to date anywhere in the world. Recent archaeological work has yielded behaviorally modified stones, dated by chronometric means to 4,300 years of age, lodging starch residue suggestive of prehistoric dietary practices by ancient chimpanzees. The "Chimpanzee Stone Age" pre-dates the advent of settled farming villages in this part of the African rainforest and suggests that percussive material culture could have been inherited from an common human-chimpanzee clade, rather than invented by hominins, or have arisen by imitation, or resulted from independent technological convergence.

  3. Genome-wide comparative analysis reveals human-mouse regulatory landscape and evolution.

    Science.gov (United States)

    Denas, Olgert; Sandstrom, Richard; Cheng, Yong; Beal, Kathryn; Herrero, Javier; Hardison, Ross C; Taylor, James

    2015-02-14

    Because species-specific gene expression is driven by species-specific regulation, understanding the relationship between sequence and function of the regulatory regions in different species will help elucidate how differences among species arise. Despite active experimental and computational research, relationships among sequence, conservation, and function are still poorly understood. We compared transcription factor occupied segments (TFos) for 116 human and 35 mouse TFs in 546 human and 125 mouse cell types and tissues from the Human and the Mouse ENCODE projects. We based the map between human and mouse TFos on a one-to-one nucleotide cross-species mapper, bnMapper, that utilizes whole genome alignments (WGA). Our analysis shows that TFos are under evolutionary constraint, but a substantial portion (25.1% of mouse and 25.85% of human on average) of the TFos does not have a homologous sequence on the other species; this portion varies among cell types and TFs. Furthermore, 47.67% and 57.01% of the homologous TFos sequence shows binding activity on the other species for human and mouse respectively. However, 79.87% and 69.22% is repurposed such that it binds the same TF in different cells or different TFs in the same cells. Remarkably, within the set of repurposed TFos, the corresponding genome regions in the other species are preferred locations of novel TFos. These events suggest exaptation of some functional regulatory sequences into new function. Despite TFos repurposing, we did not find substantial changes in their predicted target genes, suggesting that CRMs buffer evolutionary events allowing little or no change in the TFos - target gene associations. Thus, the small portion of TFos with strictly conserved occupancy underestimates the degree of conservation of regulatory interactions. We mapped regulatory sequences from an extensive number of TFs and cell types between human and mouse using WGA. A comparative analysis of this correspondence unveiled the

  4. Chimpanzees trust conspecifics to engage in low-cost reciprocity.

    Science.gov (United States)

    Engelmann, Jan M; Herrmann, Esther; Tomasello, Michael

    2015-02-22

    Many of humans' most important social interactions rely on trust, including most notably among strangers. But little is known about the evolutionary roots of human trust. We presented chimpanzees (Pan troglodytes) with a modified version of the human trust game--trust in reciprocity--in which subjects could opt either to obtain a small but safe reward on their own or else to send a larger reward to a partner and trust her to reciprocate a part of the reward that she could not access herself. In a series of three studies, we found strong evidence that in interacting with a conspecific, chimpanzees show spontaneous trust in a novel context; flexibly adjust their level of trust to the trustworthiness of their partner and develop patterns of trusting reciprocity over time. At least in some contexts then, trust in reciprocity is not unique to humans, but rather has its evolutionary roots in the social interactions of humans' closest primate relatives. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  5. Muscle-specific integrins in masseter muscle fibers of chimpanzees: an immunohistochemical study.

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    Gianluigi Vaccarino

    2010-05-01

    Full Text Available Most notably, recent comparative genomic analyses strongly indicate that the marked differences between modern human and chimpanzees are likely due more to changes in gene regulation than to modifications of the genes. The most peculiar aspect of hominoid karyotypes is that human have 46 chromosomes whereas gorillas and chimpanzees have 48. Interestingly, human and chimpanzees do share identical inversions on chromosome 7 and 9 that are not evident in the gorilla karyotype. Thus, the general phylogeny suggests that humans and chimpanzees are sister taxa; based on this, it seems that human-chimpanzee sequence similarity is an astonishing 99%. At this purpose, of particular interest is the inactivation of the myosin heavy chain 16 (MYH16 gene, most prominently expressed in the masticatory muscle of mammals. It has been showed that the loss of this gene in humans may have resulted in smaller masticatory muscle and consequential changes to cranio-facial morphology and expansion of the human brain case. Powerful masticatory muscles are found in most primates; contrarily, in both modern and fossil member Homo, these muscles are considerably smaller. The evolving hominid masticatory apparatus shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo. To better comprehend the real role of the MYH16 gene, we studied the primary proteins present in the muscle fibers of humans and non-humans, in order to understand if they really can be influenced by MYH16 gene. At this aim we examined the muscle-specific integrins, alpha 7B and beta 1D-integrins, and their relative fetal isoforms, alpha 7A and beta 1A-integrins, analyzing, by immunohistochemistry, muscle biopsies of two components of a chimpanzee's group in captivity, an alpha male and a non-alpha male subjects; all these integrins participate in vital biological processes such as maintenance of tissue integrity, embryonic development, cell

  6. Bonobos fall within the genomic variation of chimpanzees.

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    Anne Fischer

    Full Text Available To gain insight into the patterns of genetic variation and evolutionary relationships within and between bonobos and chimpanzees, we sequenced 150,000 base pairs of nuclear DNA divided among 15 autosomal regions as well as the complete mitochondrial genomes from 20 bonobos and 58 chimpanzees. Except for western chimpanzees, we found poor genetic separation of chimpanzees based on sample locality. In contrast, bonobos consistently cluster together but fall as a group within the variation of chimpanzees for many of the regions. Thus, while chimpanzees retain genomic variation that predates bonobo-chimpanzee speciation, extensive lineage sorting has occurred within bonobos such that much of their genome traces its ancestry back to a single common ancestor that postdates their origin as a group separate from chimpanzees.

  7. GATM, the human ortholog of the mouse imprinted Gatm gene, escapes genomic imprinting in placenta

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    Toshinobu Miyamoto

    2005-03-01

    Full Text Available The GATM gene encodes L-arginine:glycine amidinotransferase, which catalyzes the conversion of L-arginine into guanidinoacetate, the rate-limiting step in the synthesis of creatine. Since, deficiencies in creatine synthesis and transport lead to certain forms of mental retardation in human, the human GATM gene appears to be involved in brain development. Recently it has been demonstrated that the mouse Gatm is expressed during development and is imprinted with maternal expression in the placenta and yolk sac, but not in embryonic tissues. We investigated the imprinting status of the human GATM by analyzing its expression in four human placentas. GATM was biallelically expressed, thus suggesting that this gene escapes genomic imprinting in placentas, differently from what has been reported in mouse extra-embryonic tissues.

  8. A human lung xenograft mouse model of Nipah virus infection.

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    Gustavo Valbuena

    2014-04-01

    Full Text Available Nipah virus (NiV is a member of the genus Henipavirus (family Paramyxoviridae that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%. NiV can cause Acute Lung Injury (ALI in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7 TCID50/gram lung tissue as early as 3 days post infection (pi. NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

  9. Comparative genetics: synergizing human and NOD mouse studies for identifying genetic causation of type 1 diabetes.

    Science.gov (United States)

    Driver, John P; Chen, Yi-Guang; Mathews, Clayton E

    2012-01-01

    Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.

  10. Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants

    NARCIS (Netherlands)

    Schuitemaker, H.; Meyaard, L.; Kootstra, N. A.; Dubbes, R.; Otto, S. A.; Tersmette, M.; Heeney, J. L.; Miedema, F.

    1993-01-01

    In asymptomatic human immunodeficiency virus (HIV) infection in humans, disturbed T cell functions such as anergy and programmed cell death, thought to result from inappropriate signaling by antigen-presenting cells due to HIV infection, precede increase in virus load, decline in CD4+ T cell

  11. ¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.

    Science.gov (United States)

    Hulsey, Keith M; Mashimo, Tomoyuki; Banerjee, Abhishek; Soesbe, Todd C; Spence, Jeffrey S; Vemireddy, Vamsidhara; Maher, Elizabeth A; Bachoo, Robert M; Choi, Changho

    2015-01-01

    Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees.

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    Weimin Liu

    2008-07-01

    Full Text Available Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2 and Ebola virus. Simian foamy viruses (SFVs are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724 were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706 or viral nucleic acids (n = 392. SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz; however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp, pol-RT (717 bp, and pol-IN (425 bp sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey

  13. Chimpanzees and bonobos exhibit emotional responses to decision outcomes.

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    Alexandra G Rosati

    Full Text Available The interface between cognition, emotion, and motivation is thought to be of central importance in understanding complex cognitive functions such as decision-making and executive control in humans. Although nonhuman apes have complex repertoires of emotional expression, little is known about the role of affective processes in ape decision-making. To illuminate the evolutionary origins of human-like patterns of choice, we investigated decision-making in humans' closest phylogenetic relatives, chimpanzees (Pan troglodytes and bonobos (Pan paniscus. In two studies, we examined these species' temporal and risk preferences, and assessed whether apes show emotional and motivational responses in decision-making contexts. We find that (1 chimpanzees are more patient and more risk-prone than are bonobos, (2 both species exhibit affective and motivational responses following the outcomes of their decisions, and (3 some emotional and motivational responses map onto species-level and individual-differences in decision-making. These results indicate that apes do exhibit emotional responses to decision-making, like humans. We explore the hypothesis that affective and motivational biases may underlie the psychological mechanisms supporting value-based preferences in these species.

  14. Vocal learning in the functionally referential food grunts of chimpanzees.

    Science.gov (United States)

    Watson, Stuart K; Townsend, Simon W; Schel, Anne M; Wilke, Claudia; Wallace, Emma K; Cheng, Leveda; West, Victoria; Slocombe, Katie E

    2015-02-16

    One standout feature of human language is our ability to reference external objects and events with socially learned symbols, or words. Exploring the phylogenetic origins of this capacity is therefore key to a comprehensive understanding of the evolution of language. While non-human primates can produce vocalizations that refer to external objects in the environment, it is generally accepted that their acoustic structure is fixed and a product of arousal states. Indeed, it has been argued that the apparent lack of flexible control over the structure of referential vocalizations represents a key discontinuity with language. Here, we demonstrate vocal learning in the acoustic structure of referential food grunts in captive chimpanzees. We found that, following the integration of two groups of adult chimpanzees, the acoustic structure of referential food grunts produced for a specific food converged over 3 years. Acoustic convergence arose independently of preference for the food, and social network analyses indicated this only occurred after strong affiliative relationships were established between the original subgroups. We argue that these data represent the first evidence of non-human animals actively modifying and socially learning the structure of a meaningful referential vocalization from conspecifics. Our findings indicate that primate referential call structure is not simply determined by arousal and that the socially learned nature of referential words in humans likely has ancient evolutionary origins. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Chimpanzee genomic diversity reveals ancient admixture with bonobos

    DEFF Research Database (Denmark)

    de Manuel, Marc; Kuhlwilm, Martin; Frandsen, Peter

    2016-01-01

    Our closest living relatives, chimpanzees and bonobos, have a complex demographic history. We analyzed the high-coverage whole genomes of 75 wild-born chimpanzees and bonobos from 10 countries in Africa. We found that chimpanzee population substructure makes genetic information a good predictor...

  16. A Novel Class of Small Molecule Agonists with Preference for Human over Mouse TLR4 Activation.

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    Jason D Marshall

    Full Text Available The best-characterized Toll-like receptor 4 (TLR4 ligands are lipopolysaccharide (LPS and its chemically modified and detoxified variant, monophosphoryl lipid A (MPL. Although both molecules are active for human TLR4, they demonstrate a potency preference for mouse TLR4 based on data from transfected cell lines and primary cells of both species. After a high throughput screening process of small molecule libraries, we have discovered a new class of TLR4 agonist with a species preference profile differing from MPL. Products of the 4-component Ugi synthesis reaction were demonstrated to potently trigger human TLR4-transfected HEK cells but not mouse TLR4, although inclusion of the human MD2 with mTLR4 was able to partially recover activity. Co-expression of CD14 was not required for optimal activity of Ugi compounds on transfected cells, as it is for LPS. The species preference profile for the panel of Ugi compounds was found to be strongly active for human and cynomolgus monkey primary cells, with reduced but still substantial activity for most Ugi compounds on guinea pig cells. Mouse, rat, rabbit, ferret, and cotton rat cells displayed little or no activity when exposed to Ugi compounds. However, engineering the human versions of TLR4 and MD2 to be expressed in mTLR4/MD2 deficient mice allowed for robust activity by Ugi compounds both in vitro and in vivo. These findings extend the range of compounds available for development as agonists of TLR4 and identify novel molecules which reverse the TLR4 triggering preference of MPL for mouse TLR4 over human TLR4. Such compounds may be amenable to formulation as more potent human-specific TLR4L-based adjuvants than typical MPL-based adjuvants.

  17. Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy

    Science.gov (United States)

    Douglas, Darlene S.; Popko, Brian

    2009-01-01

    Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175

  18. Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

    Science.gov (United States)

    Nakagawa, Shin-ichiro; Hirata, Yuichi; Kameyama, Takeshi; Tokunaga, Yuko; Nishito, Yasumasa; Hirabayashi, Kazuko; Yano, Junichi; Ochiya, Takahiro; Tateno, Chise; Tanaka, Yasuhito; Mizokami, Masashi; Tsukiyama-Kohara, Kyoko; Inoue, Kazuaki; Yoshiba, Makoto; Takaoka, Akinori; Kohara, Michinori

    2013-01-01

    The interferon (IFN) system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV) and hepatitis B virus (HBV). This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC). Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs) in the livers and sera of these humanized chimeric mice. Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level) of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic) tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1), suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection.

  19. Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

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    Shin-ichiro Nakagawa

    Full Text Available BACKGROUND & AIMS: The interferon (IFN system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV and hepatitis B virus (HBV. METHODS: This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC. Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs in the livers and sera of these humanized chimeric mice. RESULTS: Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1, suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. CONCLUSIONS: These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection.

  20. A chimpanzee recognizes synthetic speech with significantly reduced acoustic cues to phonetic content.

    Science.gov (United States)

    Heimbauer, Lisa A; Beran, Michael J; Owren, Michael J

    2011-07-26

    A long-standing debate concerns whether humans are specialized for speech perception, which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words, asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuographic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users. Experiment 2 tested "impossibly unspeechlike" sine-wave (SW) synthesis, which reduces speech to just three moving tones. Although receiving only intermittent and noncontingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate but improved in experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. The Extraordinary Nature of Barney's Drumming : A Complementary Study of Ordinary Noise Making in Chimpanzees

    NARCIS (Netherlands)

    Dufour, Valérie; Pasquaretta, Cristian; Gayet, Pierre; Sterck, Elisabeth H M

    In a previous study (Dufour et al., 2015) we reported the unusual characteristics of the drumming performance of a chimpanzee named Barney. His sound production, several sequences of repeated drumming on an up-turned plastic barrel, shared features typical for human musical drumming: it was

  2. Chimpanzees (Pan troglodytes) and the question of cumulative culture: an experimental approach.

    Science.gov (United States)

    Marshall-Pescini, Sarah; Whiten, Andrew

    2008-07-01

    There is increasing evidence for cultural variations in behaviour among non-human species, but human societies additionally display elaborate cumulative cultural evolution, with successive generations building on earlier achievements. Evidence for cumulative culture in non-human species remains minimal and controversial. Relevant experiments are also lacking. Here we present a first experiment designed to examine chimpanzees' capacity for cumulative social learning. Eleven young chimpanzees were presented with a foraging device, which afforded both a relatively simple and a more complex tool-use technique for extracting honey. The more complex 'probing' technique incorporated the core actions of the simpler 'dipping' one and was also much more productive. In a baseline, exploration condition only two subjects discovered the dipping technique and a solitary instance of probing occurred. Demonstrations of dipping by a familiar human were followed by acquisition of this technique by the five subjects aged three years or above, whilst younger subjects showed a significant increase only in the elements of the dipping technique. By contrast, subsequent demonstrations of the probing task were not followed by acquisition of this more productive technique. Subjects stuck to their habitual dipping method despite an escalating series of demonstrations eventually exceeding 200. Supplementary tests showed this technique is within the capability of chimpanzees of this age. We therefore tentatively conclude that young chimpanzees exhibit a tendency to become 'stuck' on a technique they initially learn, inhibiting cumulative social learning and possibly constraining the species' capacity for cumulative cultural evolution.

  3. Dogs (Canis familiaris, but not chimpanzees (Pan troglodytes, understand imperative pointing.

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    Katharina C Kirchhofer

    Full Text Available Chimpanzees routinely follow the gaze of humans to outside targets. However, in most studies using object choice they fail to use communicative gestures (e.g. pointing to find hidden food. Chimpanzees' failure to do this may be due to several difficulties with this paradigm. They may, for example, misinterpret the gesture as referring to the opaque cup instead of the hidden food. Or perhaps they do not understand informative communicative intentions. In contrast, dogs seem to be skilful in using human communicative cues in the context of finding food, but as of yet there is not much data showing whether they also use pointing in the context of finding non-food objects. Here we directly compare chimpanzees' (N = 20 and dogs' (N = 32 skills in using a communicative gesture directed at a visible object out of reach of the human but within reach of the subject. Pairs of objects were placed in view of and behind the subjects. The task was to retrieve the object the experimenter wanted. To indicate which one she desired, the experimenter pointed imperatively to it and directly rewarded the subject for handing over the correct one. While dogs performed well on this task, chimpanzees failed to identify the referent. Implications for great apes' and dogs' understanding of human communicative intentions are discussed.

  4. Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees

    NARCIS (Netherlands)

    Lauw, F. N.; Dekkers, P. E.; te Velde, A. A.; Speelman, P.; Levi, M. [=Marcel M.; Kurimoto, M.; Hack, C. E.; van Deventer, S. J.; van der Poll, T.

    1999-01-01

    To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 microg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-gamma (IFN-gamma), plus a marked

  5. MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones.

    Science.gov (United States)

    El Kennani, Sara; Adrait, Annie; Shaytan, Alexey K; Khochbin, Saadi; Bruley, Christophe; Panchenko, Anna R; Landsman, David; Pflieger, Delphine; Govin, Jérôme

    2017-01-01

    Histones and histone variants are essential components of the nuclear chromatin. While mass spectrometry has opened a large window to their characterization and functional studies, their identification from proteomic data remains challenging. Indeed, the current interpretation of mass spectrometry data relies on public databases which are either not exhaustive (Swiss-Prot) or contain many redundant entries (UniProtKB or NCBI). Currently, no protein database is ideally suited for the analysis of histones and the complex array of mammalian histone variants. We propose two proteomics-oriented manually curated databases for mouse and human histone variants. We manually curated >1700 gene, transcript and protein entries to produce a non-redundant list of 83 mouse and 85 human histones. These entries were annotated in accordance with the current nomenclature and unified with the "HistoneDB2.0 with Variants" database. This resource is provided in a format that can be directly read by programs used for mass spectrometry data interpretation. In addition, it was used to interpret mass spectrometry data acquired on histones extracted from mouse testis. Several histone variants, which had so far only been inferred by homology or detected at the RNA level, were detected by mass spectrometry, confirming the existence of their protein form. Mouse and human histone entries were collected from different databases and subsequently curated to produce a non-redundant protein-centric resource, MS_HistoneDB. It is dedicated to the proteomic study of histones in mouse and human and will hopefully facilitate the identification and functional study of histone variants.

  6. Spontaneous reoccurrence of “scooping”, a wild tool-use behaviour, in naïve chimpanzees

    Directory of Open Access Journals (Sweden)

    Elisa Bandini

    2017-09-01

    Full Text Available Modern human technological culture depends on social learning. A widespread assumption for chimpanzee tool-use cultures is that they, too, are dependent on social learning. However, we provide evidence to suggest that individual learning, rather than social learning, is the driver behind determining the form of these behaviours within and across individuals. Low-fidelity social learning instead merely facilitates the reinnovation of these behaviours, and thus helps homogenise the behaviour across chimpanzees, creating the population-wide patterns observed in the wild (what here we call “socially mediated serial reinnovations”. This is the main prediction of the Zone of Latent Solutions (ZLS hypothesis. This study directly tested the ZLS hypothesis on algae scooping, a wild chimpanzee tool-use behaviour. We provided naïve chimpanzees (n = 14, Mage = 31.33, SD = 10.09 with ecologically relevant materials of the wild behaviour but, crucially, without revealing any information on the behavioural form required to accomplish this task. This study found that naïve chimpanzees expressed the same behavioural form as their wild counterparts, suggesting that, as the ZLS theory predicts, individual learning is the driver behind the frequency of this behavioural form. As more behaviours are being found to be within chimpanzee’s ZLS, this hypothesis now provides a parsimonious explanation for chimpanzee tool cultures.

  7. The effect of canopy closure on chimpanzee nest abundance in Lagoas de Cufada National Park, Guinea-Bissau.

    Science.gov (United States)

    Sousa, Joana; Casanova, Catarina; Barata, André V; Sousa, Cláudia

    2014-04-01

    The present study aimed to gather baseline information about chimpanzee nesting and density in Lagoas de Cufada Natural Park (LCNP), in Guinea-Bissau. Old and narrow trails were followed to estimate chimpanzee density through marked-nest counts and to test the effect of canopy closure (woodland savannah, forest with a sparse canopy, and forest with a dense canopy) on nest distribution. Chimpanzee abundance was estimated at 0.79 nest builders/km(2), the lowest among the areas of Guinea-Bissau with currently studied chimpanzee populations. Our data suggest that sub-humid forest with a dense canopy accounts for significantly higher chimpanzee nest abundance (1.50 nests/km of trail) than sub-humid forest with a sparse canopy (0.49 nests/km of trail) or woodland savannah (0.30 nests/km of trail). Dense-canopy forests play an important role in chimpanzee nesting in the patchy and highly humanized landscape of LCNP. The tree species most frequently used for nesting are Dialium guineense (46%) and Elaeis guineensis (28%). E. guineensis contain nests built higher in the canopy, while D. guineense contain nests built at lower heights. Nests observed during baseline sampling and replications suggest seasonal variations in the tree species used for nest building.

  8. A mouse following in the footsteps of human prehistory.

    Science.gov (United States)

    Vohr, Samuel H; Green, Richard E

    2013-02-14

    One of the strongest signals of positive selection in humans surrounds the V370A variant of Ectodysplasin A receptor (EDAR). However, its phenotypic consequences and impetus for selection are not well understood. Kamberov et al. nail down when it originated and, using transgenic mice, delineate its phenotypic impacts. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Endothelial and lipoprotein lipases in human and mouse placenta

    DEFF Research Database (Denmark)

    Lindegaard, Marie L S; Olivecrona, Gunilla; Christoffersen, Christina

    2005-01-01

    Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta. When placental protein extracts were separated by heparin-Sepharos...

  10. The influence of body mass index, age and sex on inflammatory disease risk in semi-captive Chimpanzees.

    Directory of Open Access Journals (Sweden)

    Vincent Obanda

    Full Text Available Obesity and ageing are emerging issues in the management of captive primates, including Chimpanzees, Pan troglodytes. Studies on humans show that obesity and old age can independently increase the risk of inflammatory-associated diseases indicated by elevated levels of pro-inflammatory cells and proteins in the blood of older or obese compared to levels in younger or non-obese individuals. In humans, sex can influence the outcomes of these risks. Health management of these problems in chimpanzee populations requires an understanding of similarities and differences of factors influencing inflammatory disease risks in humans and in chimpanzees. We examined the relationship between age, sex and Body Mass Index (BMI with hematological biomarkers of inflammatory disease risk established for humans which include the neutrophil to lymphocyte ratio (NLR, and neutrophil, white blood cell (WBC, platelet microparticle and platelet counts. We found that higher values of NLR, neutrophil count and platelet microparticle count were associated with higher BMI values and older age indicating increased inflammation risk in these groups; a similar pattern to humans. There was a strong sex by age interaction on inflammation risk, with older males more at risk than older females. In contrast to human studies, total WBC count was not influenced by BMI, but like humans, WBC and platelet counts were lower in older individuals compared to younger individuals. Our findings are similar to those of humans and suggest that further insight on managing chimpanzees can be gained from extensive studies of ageing and obesity in humans. We suggest that managing BMI should be an integral part of health management in captive chimpanzee populations in order to partially reduce the risk of diseases associated with inflammation. These results also highlight parallels in inflammation risk between humans and chimpanzees and have implications for understanding the evolution of

  11. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.

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    Jean-Philippe Coppé

    2010-02-01

    Full Text Available Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP, which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that "senescent" mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen, do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3% oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-alpha. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.

  12. Development and Characterization of a Human and Mouse Intestinal Epithelial Cell Monolayer Platform

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    Kenji Kozuka

    2017-12-01

    Full Text Available Summary: We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages. Ion transport phenotypes of monolayers from the proximal and distal colon and small intestine matched the known and unique physiology of these intestinal segments. The cultures secreted serotonin, GLP-1, and FGF19 and upregulated the epithelial sodium channel in response to known biologically active agents, suggesting intact secretory and absorptive functions. A screen of over 2,000 pharmacologically active compounds for inhibition of potassium ion transport in the mouse distal colon cultures led to the identification of a tool compound. : Siegel and colleagues describe their development of a human and mouse intestinal epithelial cell monolayer platform that maintains the cellular, molecular, and functional characteristics of tissue for each intestinal segment. They demonstrate the platform's application to drug discovery by screening a library of over 2,000 compounds to identify an inhibitor of potassium ion transport in the mouse distal colon. Keywords: intestinal epithelium, organoids, monolayer, colon, small intestine, phenotype screening assays, enteroid, colonoid

  13. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Science.gov (United States)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  14. Usability of human Infinium MethylationEPIC BeadChip for mouse DNA methylation studies.

    Science.gov (United States)

    Needhamsen, Maria; Ewing, Ewoud; Lund, Harald; Gomez-Cabrero, David; Harris, Robert Adam; Kular, Lara; Jagodic, Maja

    2017-11-15

    The advent of array-based genome-wide DNA methylation methods has enabled quantitative measurement of single CpG methylation status at relatively low cost and sample input. Whereas the use of Infinium Human Methylation BeadChips has shown great utility in clinical studies, no equivalent tool is available for rodent animal samples. We examined the feasibility of using the new Infinium MethylationEPIC BeadChip for studying DNA methylation in mouse. In silico, we identified 19,420 EPIC probes (referred as mEPIC probes), which align with a unique best alignment score to the bisulfite converted reference mouse genome mm10. Further annotation revealed that 85% of mEPIC probes overlapped with mm10.refSeq genes at different genomic features including promoters (TSS1500 and TSS200), 1st exons, 5'UTRs, 3'UTRs, CpG islands, shores, shelves, open seas and FANTOM5 enhancers. Hybridization of mouse samples to Infinium Human MethylationEPIC BeadChips showed successful measurement of mEPIC probes and reproducibility between inter-array biological replicates. Finally, we demonstrated the utility of mEPIC probes for data exploration such as hierarchical clustering. Given the absence of cost and labor convenient genome-wide technologies in the murine system, our findings show that the Infinium MethylationEPIC BeadChip platform is suitable for investigation of the mouse methylome. Furthermore, we provide the "mEPICmanifest" with genomic features, available to users of Infinium Human MethylationEPIC arrays for mouse samples.

  15. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

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    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  16. Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN

    NARCIS (Netherlands)

    Geijtenbeek, T. B.; Koopman, G.; van Duijnhoven, G. C.; van Vliet, S. J.; van Schijndel, A. C.; Engering, A.; Heeney, J. L.; van Kooyk, Y.

    2001-01-01

    Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a

  17. Genetic regulation of pituitary gland development in human and mouse.

    Science.gov (United States)

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T

    2009-12-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.

  18. Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with KitWv Mutations

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    Ayano Yurino

    2016-09-01

    Full Text Available In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous KitWv mutations into C57BL/6.Rag2nullIl2rgnull mice with NOD-Sirpa (BRGS strongly promoted human multi-lineage reconstitution. After xenotransplantation of human CD34+CD38− cord blood cells, these newly generated C57BL/6.Rag2nullIl2rgnullNOD-Sirpa KitWv/Wv (BRGSKWv/Wv mice showed significantly higher levels of human cell chimerism and long-term multi-lineage reconstitution compared with BRGS mice. Strikingly, this mouse displayed a robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow. Furthermore, depletion of host macrophages by clodronate administration resulted in the presence of human erythrocytes and platelets in the circulation. Thus, attenuation of mouse KIT signaling greatly enhances the multi-lineage differentiation of human hematopoietic stem and progenitor cells (HSPCs in mouse bone marrow, presumably by outcompeting mouse HSPCs to occupy suitable microenvironments. The BRGSKWv/Wv mouse model is a useful tool to study human multi-lineage hematopoiesis.

  19. Travel fosters tool use in wild chimpanzees.

    Science.gov (United States)

    Gruber, Thibaud; Zuberbühler, Klaus; Neumann, Christof

    2016-07-19

    Ecological variation influences the appearance and maintenance of tool use in animals, either due to necessity or opportunity, but little is known about the relative importance of these two factors. Here, we combined long-term behavioural data on feeding and travelling with six years of field experiments in a wild chimpanzee community. In the experiments, subjects engaged with natural logs, which contained energetically valuable honey that was only accessible through tool use. Engagement with the experiment was highest after periods of low fruit availability involving more travel between food patches, while instances of actual tool-using were significantly influenced by prior travel effort only. Additionally, combining data from the main chimpanzee study communities across Africa supported this result, insofar as groups with larger travel efforts had larger tool repertoires. Travel thus appears to foster tool use in wild chimpanzees and may also have been a driving force in early hominin technological evolution.

  20. The knowns and unknowns of chimpanzee culture.

    Science.gov (United States)

    Gruber, Thibaud; Reynolds, Vernon; Zuberbühler, Klaus

    2010-05-01

    Claims of culture in chimpanzees appeared soon after the launch of the first field studies in africa.1 The notion of chimpanzee 'material cultures' was coined,2 and this was followed by a first formal comparison, which revealed an astonishing degree of behavioural diversity between the different study communities, mainly in terms of tool use.3 Although this behavioural diversity is still undisputed, the question of chimpanzee cultures has remained controversial.4-6 The debate has less to do with the definition of culture (most animal behaviour researchers accept the notion for behaviour that is 'transmitted repeatedly through social or observational learning to become a population-level characteristic' 3), but more with whether some key criteria are met.

  1. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

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    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  2. A human/mouse chimeric monoclonal antibody against intercellular adhesion molecule-1 for tumor radioimmunoimaging

    International Nuclear Information System (INIS)

    Yamamura, Miyuki; Hinoda, Yuji; Sasaki, Shigeru; Tsujisaki, Masayuki; Imai, Kohzoh; Oriuchi, Noboru; Endo, Keigo.

    1996-01-01

    A mouse-human chimeric antibody for intercellular adhesion molecule-1 (ICAM-1) was established by using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The HA58 hybridoma secreted anti-ICAM-1 monoclonal antibody (MoAb) (IgG1,κ). The gene of the mouse variable region of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the HA58 hybridoma RNA. The variable region of heavy chain was joined with an expression vector which contains human γ1 constant gene. The expression vector was transfected into heavy chain loss mutant cells HA58-7, which produced only murine immunoglobulin light chains. The resultant chimeric MoAb HA58, chHA58, retained full-binding reactivity to ICAM-1 compared with murine HA58 parental antibody. The chimeric MoAb chHA58 showed little antibody dependent cell-mediated cytotoxic activity against cultured tumor cells. Biodistribution studies with 99m Tc-labeled chHA58 in nude mice bearing human gastric carcinoma JRST cells, demonstrated that the tumor-blood ratio was 1.55 at 18 h after injection, when the tumors were clearly visible in gamma scintigraphy. These data suggest that chHA58 may be of practical use for radioimmunoimaging of a wide variety of tumors. (author)

  3. Shared and Unique Proteins in Human, Mouse and Rat Saliva Proteomes: Footprints of Functional Adaptation

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    Robert C. Karn

    2013-12-01

    Full Text Available The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6 and the genome rat (BN/SsNHsd/Mcwi. Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.

  4. Chimpanzees (Pan troglodytes) Produce the Same Types of ‘Laugh Faces’ when They Emit Laughter and when They Are Silent

    Science.gov (United States)

    Davila-Ross, Marina; Jesus, Goncalo; Osborne, Jade; Bard, Kim A.

    2015-01-01

    The ability to flexibly produce facial expressions and vocalizations has a strong impact on the way humans communicate, as it promotes more explicit and versatile forms of communication. Whereas facial expressions and vocalizations are unarguably closely linked in primates, the extent to which these expressions can be produced independently in nonhuman primates is unknown. The present work, thus, examined if chimpanzees produce the same types of facial expressions with and without accompanying vocalizations, as do humans. Forty-six chimpanzees (Pan troglodytes) were video-recorded during spontaneous play with conspecifics at the Chimfunshi Wildlife Orphanage. ChimpFACS was applied, a standardized coding system to measure chimpanzee facial movements, based on FACS developed for humans. Data showed that the chimpanzees produced the same 14 configurations of open-mouth faces when laugh sounds were present and when they were absent. Chimpanzees, thus, produce these facial expressions flexibly without being morphologically constrained by the accompanying vocalizations. Furthermore, the data indicated that the facial expression plus vocalization and the facial expression alone were used differently in social play, i.e., when in physical contact with the playmates and when matching the playmates’ open-mouth faces. These findings provide empirical evidence that chimpanzees produce distinctive facial expressions independently from a vocalization, and that their multimodal use affects communicative meaning, important traits for a more explicit and versatile way of communication. As it is still uncertain how human laugh faces evolved, the ChimpFACS data were also used to empirically examine the evolutionary relation between open-mouth faces with laugh sounds of chimpanzees and laugh faces of humans. The ChimpFACS results revealed that laugh faces of humans must have gradually emerged from laughing open-mouth faces of ancestral apes. This work examines the main evolutionary

  5. Neovascular niche for human myeloma cells in immunodeficient mouse bone.

    Directory of Open Access Journals (Sweden)

    Hirono Iriuchishima

    Full Text Available The interaction with bone marrow (BM plays a crucial role in pathophysiological features of multiple myeloma (MM, including cell proliferation, chemoresistance, and bone lesion progression. To characterize the MM-BM interactions, we utilized an in vivo experimental model for human MM in which a GFP-expressing human MM cell line is transplanted into NOG mice (the NOG-hMM model. Transplanted MM cells preferentially engrafted at the metaphyseal region of the BM endosteum and formed a complex with osteoblasts and osteoclasts. A subpopulation of MM cells expressed VE-cadherin after transplantation and formed endothelial-like structures in the BM. CD138(+ myeloma cells in the BM were reduced by p53-dependent apoptosis following administration of the nitrogen mustard derivative bendamustine to mice in the NOG-hMM model. Bendamustine maintained the osteoblast lining on the bone surface and protected extracellular matrix structures. Furthermore, bendamustine suppressed the growth of osteoclasts and mesenchymal cells in the NOG-hMM model. Since VE-cadherin(+ MM cells were chemoresistant, hypoxic, and HIF-2α-positive compared to the VE-cadherin(- population, VE-cadherin induction might depend on the oxygenation status. The NOG-hMM model described here is a useful system to analyze the dynamics of MM pathophysiology, interactions of MM cells with other cellular compartments, and the utility of novel anti-MM therapies.

  6. Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.

    Science.gov (United States)

    Drake, Matthew G; Bivins-Smith, Elizabeth R; Proskocil, Becky J; Nie, Zhenying; Scott, Gregory D; Lee, James J; Lee, Nancy A; Fryer, Allison D; Jacoby, David B

    2016-09-01

    Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60-70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase-deficient transgenic mice, did not reduce eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.

  7. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    OpenAIRE

    Warimwe, GM; Lorenzo, G; Lopez-Gil, E; Reyes-Sandoval, A; Cottingham, MG; Spencer, AJ; Collins, KA; Dicks, MD; Milicic, A; Lall, A; Furze, J; Turner, AV; Hill, AV; Brun, A; Gilbert, SC

    2013-01-01

    BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibod...

  8. Vocal recruitment for joint travel in wild chimpanzees.

    Directory of Open Access Journals (Sweden)

    Thibaud Gruber

    Full Text Available Joint travel is a common social activity of many group-living animals, which requires some degree of coordination, sometimes through communication signals. Here, we studied the use of an acoustically distinct vocalisation in chimpanzees, the 'travel hoo', a signal given specifically in the travel context. We were interested in how this call type was produced to coordinate travel, whether it was aimed at specific individuals and how recipients responded. We found that 'travel hoos' were regularly given prior to impending departures and that silent travel initiations were less successful in recruiting than vocal initiations. Other behaviours associated with departure were unrelated to recruitment, suggesting that 'travel hoos' facilitated joint travel. Crucially, 'travel hoos' were more often produced in the presence of allies than other individuals, with high rates of recruitment success. We discuss these findings as evidence for how motivation to perform a specific social activity can lead to the production of a vocal signal that qualifies as 'intentional' according to most definitions, suggesting that a key psychological component of human language may have already been present in the common ancestor of chimpanzees and humans.

  9. Vocal recruitment for joint travel in wild chimpanzees.

    Science.gov (United States)

    Gruber, Thibaud; Zuberbühler, Klaus

    2013-01-01

    Joint travel is a common social activity of many group-living animals, which requires some degree of coordination, sometimes through communication signals. Here, we studied the use of an acoustically distinct vocalisation in chimpanzees, the 'travel hoo', a signal given specifically in the travel context. We were interested in how this call type was produced to coordinate travel, whether it was aimed at specific individuals and how recipients responded. We found that 'travel hoos' were regularly given prior to impending departures and that silent travel initiations were less successful in recruiting than vocal initiations. Other behaviours associated with departure were unrelated to recruitment, suggesting that 'travel hoos' facilitated joint travel. Crucially, 'travel hoos' were more often produced in the presence of allies than other individuals, with high rates of recruitment success. We discuss these findings as evidence for how motivation to perform a specific social activity can lead to the production of a vocal signal that qualifies as 'intentional' according to most definitions, suggesting that a key psychological component of human language may have already been present in the common ancestor of chimpanzees and humans.

  10. RNA isolation for transcriptomics of human and mouse small skin biopsies

    Directory of Open Access Journals (Sweden)

    Breit Timo M

    2011-10-01

    Full Text Available Abstract Background Isolation of RNA from skin biopsies presents a challenge, due to the tough nature of skin tissue and a high presence of RNases. As we lacked the dedicated equipment, i.e. homogenizer or bead-beater, needed for the available RNA from skin isolation methods, we adapted and tested our zebrafish single-embryo RNA-isolation protocol for RNA isolation from skin punch biopsies. Findings We tested our new RNA-isolation protocol in two experiments: a large-scale study with 97 human skin samples, and a small study with 16 mouse skin samples. Human skin was sampled with 4.0 mm biopsy punches and for the mouse skin different punch diameter sizes were tested; 1.0, 1.5, 2.0, and 2.5 mm. The average RNA yield in human samples was 1.5 μg with an average RNA quality RIN value of 8.1. For the mouse biopsies, the average RNA yield was 2.4 μg with an average RIN value of 7.5. For 96% of the human biopsies and 100% of the mouse biopsies we obtained enough high-quality RNA. The RNA samples were successfully tested in a transcriptomics analysis using the Affymetrix and Roche NimbleGen platforms. Conclusions Using our new RNA-isolation protocol, we were able to consistently isolate high-quality RNA, which is apt for further transcriptomics analysis. Furthermore, this method is already useable on biopsy material obtained with a punch diameter as small as 1.5 mm.

  11. Assessment of orthologous splicing isoforms in human and mouse orthologous genes

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    Horner David S

    2010-10-01

    Full Text Available Abstract Background Recent discoveries have highlighted the fact that alternative splicing and alternative transcripts are the rule, rather than the exception, in metazoan genes. Since multiple transcript and protein variants expressed by the same gene are, by definition, structurally distinct and need not to be functionally equivalent, the concept of gene orthology should be extended to the transcript level in order to describe evolutionary relationships between structurally similar transcript variants. In other words, the identification of true orthology relationships between gene products now should progress beyond primary sequence and "splicing orthology", consisting in ancestrally shared exon-intron structures, is required to define orthologous isoforms at transcript level. Results As a starting step in this direction, in this work we performed a large scale human- mouse gene comparison with a twofold goal: first, to assess if and to which extent traditional gene annotations such as RefSeq capture genuine splicing orthology; second, to provide a more detailed annotation and quantification of true human-mouse orthologous transcripts defined as transcripts of orthologous genes exhibiting the same splicing patterns. Conclusions We observed an identical exon/intron structure for 32% of human and mouse orthologous genes. This figure increases to 87% using less stringent criteria for gene structure similarity, thus implying that for about 13% of the human RefSeq annotated genes (and about 25% of the corresponding transcripts we could not identify any mouse transcript showing sufficient similarity to be confidently assigned as a splicing ortholog. Our data suggest that current gene and transcript data may still be rather incomplete - with several splicing variants still unknown. The observation that alternative splicing produces large numbers of alternative transcripts and proteins, some of them conserved across species and others truly species

  12. 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.

  13. Anti-EGFR therapy radiosensitizes human lung adenocarcinoma xenograft in nude mouse

    International Nuclear Information System (INIS)

    Wang Hui; Li Tianran; Tian Jiahe; Qu Baolin; Zhu Hui

    2008-01-01

    Objective: To investigate the effect of Gefitinib on radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. Methods: Human lung adenocarcinoma cell line A549 was used to establish nude mouse xenograft tumor model. The mice were derided into 4 groups: control, irradiation alone, Gefinitib alone and radiation combined with Genifitib. Radiation schedule was 3 fractions of 5 Gy, once daily. Gefitinib was daily administered by gavage at 100 mg/(kg·day -1 ) for 14 days. In the combination group, radiotherapy was performed 2 hours after Gefitinib administration. Tumor diameter was measured every other day. Percentage of tumor growth inhibition, growth delay time and regrowth delay time were evaluated. Results: For A549 xenografts in radiation alone, gefitinib alone and combination therapy groups, the percentage of tumor growth inhibition was 22.7%, 12.4% and 38.2%, respectively (F=25.75, P=0.000). Tumor growth delay time was 6.0, 7.8 and 21.6 days, respectively (F=70.49, P=0.000). Tumor regrowth delay time in combination therapy and irradiation alone groups was 23.4 and 10.2 days. (F=174.24, P= 0.000). Sensitizing enhancement ratio of combination group was 1.5 in growth and 1.7 in regrowth. Conclusions: Anti-EGFR therapy enhances the radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. (authors)

  14. Chimpanzees create and modify probe tools functionally: A study with zoo-housed chimpanzees.

    Science.gov (United States)

    Hopper, Lydia M; Tennie, Claudio; Ross, Stephen R; Lonsdorf, Elizabeth V

    2015-02-01

    Chimpanzees (Pan troglodytes) use tools to probe for out-of-reach food, both in the wild and in captivity. Beyond gathering appropriately-sized materials to create tools, chimpanzees also perform secondary modifications in order to create an optimized tool. In this study, we recorded the behavior of a group of zoo-housed chimpanzees when presented with opportunities to use tools to probe for liquid foods in an artificial termite mound within their enclosure. Previous research with this group of chimpanzees has shown that they are proficient at gathering materials from within their environment in order to create tools to probe for the liquid food within the artificial mound. Extending beyond this basic question, we first asked whether they only made and modified probe tools when it was appropriate to do so (i.e. when the mound was baited with food). Second, by collecting continuous data on their behavior, we also asked whether the chimpanzees first (intentionally) modified their tools prior to probing for food or whether such modifications occurred after tool use, possibly as a by-product of chewing and eating the food from the tools. Following our predictions, we found that tool modification predicted tool use; the chimpanzees began using their tools within a short delay of creating and modifying them, and the chimpanzees performed more tool modifying behaviors when food was available than when they could not gain food through the use of probe tools. We also discuss our results in terms of the chimpanzees' acquisition of the skills, and their flexibility of tool use and learning. © 2014 Wiley Periodicals, Inc.

  15. Tactile mouse generating velvet hand illusion on human palm

    Directory of Open Access Journals (Sweden)

    Nadar Rajaei

    2016-09-01

    Full Text Available To enhance virtual reality (VR generated by tactile displays, we have focused on a novel tactile illusion, called the Velvet Hand Illusion (VHI. In VHI, moving two parallel wires back and forth between the two hands leads humans to perceive a velvet-like surface between their hands. In earlier studies, we revealed that the intensity of VHI could be controlled by a ratio (r/D, where r and D are the wire stroke and wire distance, respectively. According to these findings, we investigate in this study whether a common tactile display is able to produce VHI, and whether the ratio can also control VHI intensity. We prepare a dot-matrix display as a tactile display in which moving one line of the display’s pins is considered as a wire pattern. We investigate the VHI intensity with regard to changing the stroke r and the line distance D using paired comparison. Experimental results show that the VHI intensity is increased or decreased by changing r and D. We conclude that VHI can be created by the tactile display, and the intensity of VHI is controlled by changing the ratio of r/D.

  16. DRD4 genotype predicts longevity in mouse and human.

    Science.gov (United States)

    Grady, Deborah L; Thanos, Panayotis K; Corrada, Maria M; Barnett, Jeffrey C; Ciobanu, Valentina; Shustarovich, Diana; Napoli, Anthony; Moyzis, Alexandra G; Grandy, David; Rubinstein, Marcelo; Wang, Gene-Jack; Kawas, Claudia H; Chen, Chuansheng; Dong, Qi; Wang, Eric; Volkow, Nora D; Moyzis, Robert K

    2013-01-02

    Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90-109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7-45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10(-9)), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.

  17. Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes.

    Science.gov (United States)

    Chen, Yang; Gao, Zhen; Wang, Bingcheng; Xu, Rong

    2016-08-22

    Glioblastoma (GBM) is the most common and aggressive brain tumors. It has poor prognosis even with optimal radio- and chemo-therapies. Since GBM is highly heterogeneous, drugs that target on specific molecular profiles of individual tumors may achieve maximized efficacy. Currently, the Cancer Genome Atlas (TCGA) projects have identified hundreds of GBM-associated genes. We develop a drug repositioning approach combining disease genomics and mouse phenotype data towards predicting targeted therapies for GBM. We first identified disease specific mouse phenotypes using the most recently discovered GBM genes. Then we systematically searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM. We evaluated the ranks for approved and novel GBM drugs, and compared with an existing approach, which also use the mouse phenotype data but not the disease genomics data. We achieved significantly higher ranks for the approved and novel GBM drugs than the earlier approach. For all positive examples of GBM drugs, we achieved a median rank of 9.2 45.6 of the top predictions have been demonstrated effective in inhibiting the growth of human GBM cells. We developed a computational drug repositioning approach based on both genomic and phenotypic data. Our approach prioritized existing GBM drugs and outperformed a recent approach. Overall, our approach shows potential in discovering new targeted therapies for GBM.

  18. Mechanisms of complement activation by dextran-coated superparamagnetic iron oxide (SPIO) nanoworms in mouse versus human serum

    DEFF Research Database (Denmark)

    Banda, Nirmal K; Mehta, Gaurav; Chao, Ying

    2014-01-01

    BACKGROUND: The complement system is a key component of innate immunity implicated in the neutralization and clearance of invading pathogens. Dextran coated superparamagnetic iron oxide (SPIO) nanoparticle is a promising magnetic resonance imaging (MRI) contrast agent. However, dextran SPIO has...... the mechanisms of human complement activation. Mouse data were analyzed by non-paired t-test, human data were analyzed by ANOVA followed by multiple comparisons with Student-Newman-Keuls test. RESULTS: In mouse sera, SPIO NW triggered the complement activation via the LP, whereas the AP contributes via...... the CP, but that did not affect the total level of C3 deposition on the particles. CONCLUSIONS: There were important differences and similarities in the complement activation by SPIO NW in mouse versus human sera. Understanding the mechanisms of immune recognition of nanoparticles in mouse and human...

  19. Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2005-04-01

    Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

  20. Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low pH compartment and infect cells

    International Nuclear Information System (INIS)

    Wang Enxiu; Obeng-Adjei, Nyamekye; Ying Qihua; Meertens, Laurent; Dragic, Tanya; Davey, Robert A.; Ross, Susan R.

    2008-01-01

    Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated that MMTV could induce pH 5-dependent fusion-from-with of mouse cells. Here we show that the MMTV envelope-mediated cell-cell fusion requires both the entry receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was sufficient to mediate low pH-dependent syncytia formation, virus infection required trafficking to a low pH compartment; infection was independent of cathepsin-mediated proteolysis. Human TfR1 did not support virus infection, although envelope-mediated syncytia formation occurred with human cells after pH 5 treatment and this fusion depended on TfR1 expression. However, although the MMTV envelope bound human TfR1, virus was only internalized and trafficked to a low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1 supported cell-cell fusion, because it was not internalized when bound to MMTV, it did not function as an entry receptor. Our data suggest that MMTV uses TfR1 for all steps of entry: cell attachment, induction of the conformational changes in Env required for membrane fusion and internalization to an appropriate acidic compartment

  1. Physiology of SLC12 transporters: lessons from inherited human genetic mutations and genetically engineered mouse knockouts.

    Science.gov (United States)

    Gagnon, Kenneth B; Delpire, Eric

    2013-04-15

    Among the over 300 members of the solute carrier (SLC) group of integral plasma membrane transport proteins are the nine electroneutral cation-chloride cotransporters belonging to the SLC12 gene family. Seven of these transporters have been functionally described as coupling the electrically silent movement of chloride with sodium and/or potassium. Although in silico analysis has identified two additional SLC12 family members, no physiological role has been ascribed to the proteins encoded by either the SLC12A8 or the SLC12A9 genes. Evolutionary conservation of this gene family from protists to humans confirms their importance. A wealth of physiological, immunohistochemical, and biochemical studies have revealed a great deal of information regarding the importance of this gene family to human health and disease. The sequencing of the human genome has provided investigators with the capability to link several human diseases with mutations in the genes encoding these plasma membrane proteins. The availability of bacterial artificial chromosomes, recombination engineering techniques, and the mouse genome sequence has simplified the creation of targeting constructs to manipulate the expression/function of these cation-chloride cotransporters in the mouse in an attempt to recapitulate some of these human pathologies. This review will summarize the three human disorders that have been linked to the mutation/dysfunction of the Na-Cl, Na-K-2Cl, and K-Cl cotransporters (i.e., Bartter's, Gitleman's, and Andermann's syndromes), examine some additional pathologies arising from genetically modified mouse models of these cotransporters including deafness, blood pressure, hyperexcitability, and epithelial transport deficit phenotypes.

  2. Cultura e inteligência: reflexões antropológicas sobre aspectos não físicos da evolução em chimpanzés e humanos Culture and intelligence: anthropological reflections on non-physical aspects of evolution in chimpanzees and humans

    Directory of Open Access Journals (Sweden)

    Eliane Sebeika Rapchan

    2012-09-01

    Full Text Available Trata da história recente dos estudos sobre o comportamento de chimpanzés, enfatizando os resultados das pesquisas, as proposições acerca da existência de 'culturas de chimpanzés' e sua validade. O trabalho problematiza a ideia a partir dos mecanismos de transmissão e aprendizado social bem como de concepções antropológicas e paleoantropológicas de cultura que associam tal fenômeno, entre humanos modernos, às suas capacidades simbólicas e cognitivas.The scope of this work is the recent history of studies on the behavior of chimpanzees, emphasizing research results, propositions about the existence of 'chimpanzee cultures' and their validity. The work discusses the idea based on transmission mechanisms and social learning as well as anthropological and paleoanthropological concepts of culture that associate such phenomena, among modern humans, to their symbolic and cognitive abilities.

  3. mRNA Transcriptomics of Galectins Unveils Heterogeneous Organization in Mouse and Human Brain

    Directory of Open Access Journals (Sweden)

    Sebastian John

    2016-12-01

    Full Text Available Background: Galectins, a family of non-classically secreted, β-galactoside binding proteins is involved in several brain disorders; however no systematic knowledge on the normal neuroanatomical distribution and functions of galectins exits. Hence, the major purpose of this study was to understand spatial distribution and predict functions of galectins in brain and also compare the degree of conservation vs. divergence between mouse and human species. The latter objective was required to determine the relevance and appropriateness of studying galectins in mouse brain which may ultimately enable us to extrapolate the findings to human brain physiology and pathologies.Results: In order to fill this crucial gap in our understanding of brain galectins, we analyzed the in situ hybridization (ISH and microarray data of adult mouse and human brain respectively, from the Allen Brain Atlas, to resolve each galectin-subtype’s spatial distribution across brain distinct cytoarchitecture. Next, transcription factors (TFs that may regulate galectins were identified using TRANSFAC software and the list obtained was further curated to sort TFs on their confirmed transcript expression in the adult brain. Galectin-TF cluster analysis, gene-ontology annotations and co-expression networks were then extrapolated to predict distinct functional relevance of each galectin in the neuronal processes. Data shows that galectins have highly heterogeneous expression within and across brain sub-structures and are predicted to be the crucial targets of brain enriched TFs. Lgals9 had maximal spatial distribution across mouse brain with inferred predominant roles in neurogenesis while LGALS1 was ubiquitously expressed in human. Limbic region associated with learning, memory and emotions and substantia nigra associated with motor movements showed strikingly high expression of LGALS1 and LGALS8 in human vs. mouse brain. The overall expression profile of galectin-8 was most

  4. Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

    Science.gov (United States)

    Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

    2011-12-01

    Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

  5. Wild chimpanzees are infected by Trypanosoma brucei

    Directory of Open Access Journals (Sweden)

    Milan Jirků

    2015-12-01

    Finally, we demonstrated that the mandrill serum was able to efficiently lyse T. b. brucei and T. b. rhodesiense, and to some extent T. b. gambiense, while the chimpanzee serum failed to lyse any of these subspecies.

  6. Gestation period and twinning in chimpanzees.

    Science.gov (United States)

    PEACOCK, L J; ROGERS, C M

    1959-04-10

    The length of the gestation period in 118 births in a colony of chimpanzees was found to be 226.8 days, with a standard deviation of 13.3 and a range of 196 to 260 days. Six pairs of twins were born in 120 parturitions; thus the apparent twinning rate is higher than that in man.

  7. Deadly Respiratory Disease in Wild Chimpanzees

    Centers for Disease Control (CDC) Podcasts

    2018-04-19

    Dr. Tony Goldberg, Professor of Epidemiology at the School of Veterinary Medicine and Associate Director for Research at the University of Wisconsin, Madison, Global Health Institute, discusses an outbreak of rhinovirus C in chimpanzees in Uganda.  Created: 4/19/2018 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/19/2018.

  8. Hierarchy and social status in Budongo chimpanzees.

    Science.gov (United States)

    Newton-Fisher, Nicholas E

    2004-04-01

    The status hierarchy is fundamental in the lives of male chimpanzees. This study describes the dominance interactions and social status among adult male chimpanzees of the Sonso community in the Budongo Forest Reserve, Uganda, during the period that they were first studied (1994 and 1995). Social dominance is typically measured using the behaviour of either the subordinate or the dominant individual, but a relationship is dependent on the behaviour of both parties and this study explicitly used both subordinate and dominant behaviours to investigate the status hierarchy. Among adult males of the Sonso community, agonistic interactions occurred at a low rate and pant-grunts were rare, but males could be ranked into separate hierarchies of agonistic dominance and pant-grunting (labelled 'respect') using ratios of behaviour performed/behaviour received. These hierarchies were combined to form a single hierarchy of social status that divided the males among five distinct status levels. The highest status level was held by an alliance between two males who replaced the previous alpha male during the first part of the study. Neither male in this alliance partnership pant-grunted to the other, although the reason for cooperative behaviour was unclear. Although the nominally beta male was treated as such by other adult males, he achieved surprisingly little mating success. Budongo Forest chimpanzees do not warrant the sometimes-expressed view that they are non-aggressive and peaceable and the broad pattern of their status interactions matches with that seen in other chimpanzee populations.

  9. Sexual exchange relationships in captive chimpanzees

    NARCIS (Netherlands)

    Hemelrijk, C.K.; Van Laere, G.J.; Van Hooff, J.A.R.A.M.

    1992-01-01

    In a group of captive chimpanzees (Pan troglodytes), we studied whether females received more social benefits from males when they were in oestrus than at other times and whether males distributed their beneficial acts especially to females with whom they mated more frequently. When in oestrus,

  10. [Distribution diversity of integrins and calcium channels on major human and mouse host cells of Leptospira species].

    Science.gov (United States)

    Li, Cheng-xue; Zhao, Xin; Qian, Jing; Yan, Jie

    2012-07-01

    To determine the distribution of integrins and calcium channels on major human and mouse host cells of Leptospira species. The expression of β1, β2 and β3 integrins was detected with immunofluorescence assay on the surface of human monocyte line THP-1, mouse mononuclear-macrophage-like cell line J774A.1, human vascular endothelial cell line HUVEC, mouse vascular endothelial cell EOMA, human hepatocyte line L-02, mouse hepatocyte line Hepa1-6, human renal tubular epithelial cell line HEK-293, mouse glomerular membrane epithelial cell line SV40-MES13, mouse collagen blast line NIH/3T3, human and mouse platelets. The distribution of voltage gate control calcium channels Cav3.1, Cav3.2, Cav3.3 and Cav2.3, and receptor gate calcium channels P(2)X(1), P(2)2X(2), P(2)X(3), P(2)X(4), P(2)X(5), P(2)X(6) and P(2)X(7) were determined with Western blot assay. β1 integrin proteins were positively expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, L-02, Hepa1-6 and HEK-239 cells as well as human and mouse platelets. β2 integrin proteins were expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, and NIH/3T3 cells. β3 integrin proteins were expressed on the membrane surface of J774A.1, THP-1, HUVEC, EOMA, Hepa1-6, HEK-239 and NIH/3T3 cells as well as human and mouse platelets. P(2)X(1) receptor gate calcium channel was expressed on the membrane surface of human and mouse platelets, while P(2)X(5) receptor gate calcium channel was expressed on the membrane surface of J774A.1, THP-1, L-02, Hepa1-6, HEK-239 and HUVEC cells. However, the other calcium channels were not detected on the tested cell lines or platelets. There is a large distribution diversity of integrins and calcium channel proteins on the major human and mouse host cells of Leptospira species, which may be associated with the differences of leptospira-induced injury in different host cells.

  11. Assessing chimpanzee personality and subjective well-being in Japan.

    Science.gov (United States)

    Weiss, Alexander; Inoue-Murayama, Miho; Hong, Kyung-Won; Inoue, Eiji; Udono, Toshifumi; Ochiai, Tomomi; Matsuzawa, Tetsuro; Hirata, Satoshi; King, James E

    2009-04-01

    We tested whether the cultural background of raters influenced ratings of chimpanzee personality. Our study involved comparing personality and subjective well-being ratings of 146 chimpanzees in Japan that were housed in zoos, research institutes, and a retirement sanctuary to ratings of chimpanzees in US and Australian zoos. Personality ratings were made on a translated and expanded version of a questionnaire used to rate chimpanzees in the US and Australia. Subjective well-being ratings were made on a translated version of a questionnaire used to rate chimpanzees in the US and Australia. The mean interrater reliabilities of the 43 original adjectives did not markedly differ between the present sample and the original sample of 100 zoo chimpanzees in the US. Interrater reliabilities of these samples were highly correlated, suggesting that their rank order was preserved. Comparison of the factor structures for the Japanese sample and for the original sample of chimpanzees in US zoos indicated that the overall structure was replicated and that the Dominance, Extraversion, Conscientiousness, and Agreeableness domains clearly generalized. Consistent with earlier studies, older chimpanzees had higher Dominance and lower Extraversion and Openness scores. Correlations between the six domain scores and subjective well-being were comparable to those for chimpanzees housed in the US and Australia. These findings suggest that chimpanzee personality ratings are not affected by the culture of the raters.

  12. A chimeric human-mouse model of Sjögren's syndrome.

    Science.gov (United States)

    Young, Nicholas A; Wu, Lai-Chu; Bruss, Michael; Kaffenberger, Benjamin H; Hampton, Jeffrey; Bolon, Brad; Jarjour, Wael N

    2015-01-01

    Despite recent advances in the understanding of Sjögren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2rγ(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-γ and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology. Copyright © 2014. Published by Elsevier Inc.

  13. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    International Nuclear Information System (INIS)

    Winkler, Sandra; Borkham-Kamphorst, Erawan; Stock, Peggy; Brückner, Sandra; Dollinger, Matthias; Weiskirchen, Ralf; Christ, Bruno

    2014-01-01

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH

  14. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model

    Science.gov (United States)

    Hu, Yanping; Turner, Michael J; Shields, Jacqueline; Gale, Matthew S; Hutto, Elizabeth; Roberts, Bruce L; Siders, William M; Kaplan, Johanne M

    2009-01-01

    Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on the surface of normal and malignant lymphocytes. It is approved for the treatment of B-cell chronic lymphocytic leukaemia and is undergoing Phase III clinical trials for the treatment of multiple sclerosis. The exact mechanism by which alemtuzumab mediates its biological effects in vivo is not clearly defined and mechanism of action studies have been hampered by the lack of cross-reactivity between human and mouse CD52. To address this issue, a transgenic mouse expressing human CD52 (hCD52) was created. Transgenic mice did not display any phenotypic abnormalities and were able to mount normal immune responses. The tissue distribution of hCD52 and the level of expression by various immune cell populations were comparable to those seen in humans. Treatment with alemtuzumab replicated the transient increase in serum cytokines and depletion of peripheral blood lymphocytes observed in humans. Lymphocyte depletion was not as profound in lymphoid organs, providing a possible explanation for the relatively low incidence of infection in alemtuzumab-treated patients. Interestingly, both lymphocyte depletion and cytokine induction by alemtuzumab were largely independent of complement and appeared to be mediated by neutrophils and natural killer cells because removal of these populations with antibodies to Gr-1 or asialo-GM-1, respectively, strongly inhibited the activity of alemtuzumab whereas removal of complement by treatment with cobra venom factor had no impact. The hCD52 transgenic mouse appears to be a useful model and has provided evidence for the previously uncharacterized involvement of neutrophils in the activity of alemtuzumab. PMID:19740383

  15. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [Department for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig (Germany)

    2014-08-15

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH.

  16. Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.

    Science.gov (United States)

    Koohestani, Faezeh; Qiang, Wenan; MacNeill, Amy L; Druschitz, Stacy A; Serna, Vanida A; Adur, Malavika; Kurita, Takeshi; Nowak, Romana A

    2016-07-01

    Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro. The mouse xenograft model reflects the characteristics of human leiomyomas. Primary leiomyoma smooth muscle cells from eight patients were xenografted under the renal capsule of adult, ovariectomized NOD-scid IL2Rγ(null) mice (NSG). Mice were treated with two different doses of HF or vehicle for 4 weeks with six to eight mice per group. Mouse body weight measurements and immunohistochemical analysis of body organs were carried out to assess the safety of HF treatment. Xenografted tumors were measured and analyzed for cellular and molecular changes induced by HF. Ovarian steroid hormone receptors were evaluated for possible modulation by HF. Treatment of mice carrying human UL xenografts with HF at 0.25 or 0.50 mg/kg body weight for 4 weeks resulted in a 35-40% (P leiomyoma cells in an in vivo model, HF was administered to mice whose tolerance and metabolism of the drug may differ from that in humans. Also, the longer term effects of HF treatment are yet unclear. The results of this study showing the effectiveness of HF in reducing UL tumor growth by interfering with the main cellular processes regulating cell proliferation and apoptosis are in agreement with previous studies on the effects of HF on other fibrotic diseases. HF can be considered as a candidate for reducing the size of leiomyomas, particularly prior to surgery. This project was funded by NIH PO1HD057877 and R01 HD064402. Authors report no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights

  17. The role of the placenta in the initiation of spiral artery remodelling in an early pregnant chimpanzee uterus

    DEFF Research Database (Denmark)

    Vercruysse, L; Carter, A. M.; Pijnenborg, R

    2017-01-01

    Introduction In this study we evaluated the full extent of placental bed changes (centre to periphery) in a pregnant chimpanzee uterus, kept at the Museum for Central Africa in Tervuren, Belgium. According to placental size the specimen was equivalent to an 8 weeks pregnant human uterus. Methods...... to be a feature of the placental bed as a whole, being significantly less prominent in the adjacent non-placental bed part of the uterus, indicating an effect of the presence of the placenta. The different time-course of early spiral artery remodelling in the chimpanzee as compared to the human may have had...

  18. Reproductive physiology of a humanized GnRH receptor mouse model: application in evaluation of human-specific analogs.

    Science.gov (United States)

    Tello, Javier A; Kohout, Trudy; Pineda, Rafael; Maki, Richard A; Scott Struthers, R; Millar, Robert P

    2013-07-01

    The human GnRH receptor (GNRHR1) has a specific set of properties with physiological and pharmacological influences not appropriately modeled in laboratory animals or cell-based systems. To address this deficiency, we have generated human GNRHR1 knock-in mice and described their reproductive phenotype. Measurement of pituitary GNRHR1 transcripts from homozygous human GNRHR1 knock-in (ki/ki) mice revealed a severe reduction (7- to 8-fold) compared with the mouse Gnrhr1 in wild-type mice. ¹²⁵I-GnRH binding assays on pituitary membrane fractions corroborated reduced human GNRHR1 protein expression in ki/ki mice, as occurs with transfection of human GNRHR1 in cell lines. Female homozygous knock-in mice displayed normal pubertal onset, indicating that a large reduction in GNRHR1 expression is sufficient for this process. However, ki/ki females exhibited periods of prolonged estrous and/or metestrous and reduced fertility. No impairment was found in reproductive maturity or adult fertility in male ki/ki mice. Interestingly, the serum LH response to GnRH challenge was reduced in both knock-in males and females, indicating a reduced GNRHR1 signaling capacity. Small molecules targeting human GPCRs usually have poor activities at homologous rodent receptors, thus limiting their use in preclinical development. Therefore, we tested a human-specific GnRH1 antagonist, NBI-42902, in our mouse model and demonstrated abrogation of a GnRH1-induced serum LH rise in ki/ki mice and an absence of effect in littermates expressing the wild-type murine receptor. This novel model provides the opportunity to study the human receptor in vivo and for screening the activity of human-specific GnRH analogs.

  19. DNA recovery from wild chimpanzee tools.

    Directory of Open Access Journals (Sweden)

    Fiona A Stewart

    Full Text Available Most of our knowledge of wild chimpanzee behaviour stems from fewer than 10 long-term field sites. This bias limits studies to a potentially unrepresentative set of communities known to show great behavioural diversity on small geographic scales. Here, we introduce a new genetic approach to bridge the gap between behavioural material evidence in unhabituated chimpanzees and genetic advances in the field of primatology. The use of DNA analyses has revolutionised archaeological and primatological fields, whereby extraction of DNA from non-invasively collected samples allows researchers to reconstruct behaviour without ever directly observing individuals. We used commercially available forensic DNA kits to show that termite-fishing by wild chimpanzees (Pan troglodytes schweinfurthii leaves behind detectable chimpanzee DNA evidence on tools. We then quantified the recovered DNA, compared the yield to that from faecal samples, and performed an initial assessment of mitochondrial and microsatellite markers to identify individuals. From 49 termite-fishing tools from the Issa Valley research site in western Tanzania, we recovered an average of 52 pg/μl chimpanzee DNA, compared to 376.2 pg/μl in faecal DNA extracts. Mitochondrial DNA haplotypes could be assigned to 41 of 49 tools (84%. Twenty-six tool DNA extracts yielded >25 pg/μl DNA and were selected for microsatellite analyses; genotypes were determined with confidence for 18 tools. These tools were used by a minimum of 11 individuals across the study period and termite mounds. These results demonstrate the utility of bio-molecular techniques and a primate archaeology approach in non-invasive monitoring and behavioural reconstruction of unhabituated primate populations.

  20. Franco-Japanese and other collaborative contributions to understanding chimpanzee culture at Bossou and the Nimba Mountains.

    Science.gov (United States)

    Humle, Tatyana

    2016-07-01

    The Japanese approach to science has permitted theoretical leaps in our understanding of culture in non-human animals and challenged human uniqueness, as it is not embedded in the Western traditional dualisms of human/animal and nature/culture. This paper highlights the value of an interdisciplinary approach and combining methodological approaches in exploring putative cultural variation among chimpanzees. I focus particularly on driver ants (Dorylus sp.) and oil palm (Elaeis guineensis) consumption among the Bossou and Nimba chimpanzees, in south-eastern Guinea at the border with Côte d'Ivoire and Liberia, and hand use across different tool use tasks commonly witnessed at Bossou, i.e. ant-dipping, nut-cracking, pestle-pounding, and algae-scooping. Observed variation in resource use was addressed across differing scales exploring both within- and between-community differences. Our findings have highlighted a tight interplay between ecology, social dynamics and culture, and between social and individual learning and maternal contribution to tool-use acquisition. Exploration of hand use by chimpanzees revealed no evidence for individual-level hand or community-level task specialisation. However, more complex types of tool use such as nut-cracking showed distinct lateralization, while the equivalent of a haptic manual action revealed a strong right hand bias. The data also suggest an overall population tendency for a right hand preference. As well as describing these sites' key contributions to our understanding of chimpanzees and to challenging our perceptions of human uniqueness, this paper also highlights the critical condition and high levels of threats facing this emblematic chimpanzee population, and several questions that remain to be addressed. In the spirit of the Japanese approach to science, I recommend that an interdisciplinary and collaborative research approach can best help us to challenge perceptions of human uniqueness and to further our

  1. Acupuncture as an Adjunct Therapy for Osteoarthritis in Chimpanzees (Pan troglodytes)

    Science.gov (United States)

    Magden, Elizabeth R; Haller, Rachel L; Thiele, Erica J; Buchl, Stephanie J; Lambeth, Susan P; Schapiro, Steven J

    2013-01-01

    Acupuncture is an ancient practice that is currently used to treat disorders ranging from osteoarthritis to cardiomyopathy. Acupuncture involves the insertion of thin, sterile needles into defined acupuncture points that stimulate physiologic processes through neural signaling. Numerous scientific studies have proven the benefits of acupuncture, and given this scientific support, we hypothesized that acupuncture could benefit the nonhuman primates at our facility. As our chimpanzee colony ages, we are observing an increase in osteoarthritis and have focused our initial acupuncture treatments on this condition. We successfully trained 3 chimpanzees, by using positive-reinforcement training techniques, to voluntarily participate in acupuncture treatments for stifle osteoarthritis. We used 3 acupuncture points that correlate with alleviation of stifle pain and inflammation in humans. A mobility scoring system was used to assess improvements in mobility as a function of the acupuncture treatments. The 2 chimpanzees with the most severe osteoarthritis showed significant improvement in mobility after acupuncture treatments. Acupuncture therapy not only resulted in improved mobility, but the training sessions also served as enrichment for the animals, as demonstrated by their voluntary participation in the training and treatment sessions. Acupuncture is an innovative treatment technique that our data show to be safe, inexpensive, and, most importantly, effective for chimpanzees. PMID:23849446

  2. Acupuncture as an adjunct therapy for osteoarthritis in chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Magden, Elizabeth R; Haller, Rachel L; Thiele, Erica J; Buchl, Stephanie J; Lambeth, Susan P; Schapiro, Steven J

    2013-07-01

    Acupuncture is an ancient practice that is currently used to treat disorders ranging from osteoarthritis to cardiomyopathy. Acupuncture involves the insertion of thin, sterile needles into defined acupuncture points that stimulate physiologic processes through neural signaling. Numerous scientific studies have proven the benefits of acupuncture, and given this scientific support, we hypothesized that acupuncture could benefit the nonhuman primates at our facility. As our chimpanzee colony ages, we are observing an increase in osteoarthritis and have focused our initial acupuncture treatments on this condition. We successfully trained 3 chimpanzees, by using positive-reinforcement training techniques, to voluntarily participate in acupuncture treatments for stifle osteoarthritis. We used 3 acupuncture points that correlate with alleviation of stifle pain and inflammation in humans. A mobility scoring system was used to assess improvements in mobility as a function of the acupuncture treatments. The 2 chimpanzees with the most severe osteoarthritis showed significant improvement in mobility after acupuncture treatments. Acupuncture therapy not only resulted in improved mobility, but the training sessions also served as enrichment for the animals, as demonstrated by their voluntary participation in the training and treatment sessions. Acupuncture is an innovative treatment technique that our data show to be safe, inexpensive, and, most importantly, effective for chimpanzees.

  3. Children, chimpanzees, and bonobos adjust the visibility of their actions for cooperators and competitors.

    Science.gov (United States)

    Grueneisen, Sebastian; Duguid, Shona; Saur, Heiko; Tomasello, Michael

    2017-08-17

    Chimpanzees and bonobos are highly capable of tracking other's mental states. It has been proposed, however, that in contrast to humans, chimpanzees are only able to do this in competitive interactions but this has rarely been directly tested. Here, pairs of chimpanzees or bonobos (Study 1) and 4-year-old children (Study 2) were presented with two almost identical tasks differing only regarding the social context. In the cooperation condition, players' interests were matched: they had to make corresponding choices to be mutually rewarded. To facilitate coordination, subjects should thus make their actions visible to their partner whose view was partially occluded. In the competition condition, players' interests were directly opposed: the partner tried to match the subject's choice but subjects were only rewarded if they chose differently, so that they benefited from hiding their actions. The apes successfully adapted their decisions to the social context and their performance was markedly better in the cooperation condition. Children also distinguished between the two contexts, but somewhat surprisingly, performed better in the competitive condition. These findings demonstrate experimentally that chimpanzees and bonobos can take into account what others can see in cooperative interactions. Their social-cognitive skills are thus more flexible than previously assumed.

  4. Chaînes opératoires and resource-exploitation strategies in chimpanzee (Pan troglodytes) nut cracking.

    Science.gov (United States)

    Carvalho, Susana; Cunha, Eugénia; Sousa, Cláudia; Matsuzawa, Tetsuro

    2008-07-01

    We apply archaeological methods to extend our knowledge of chimpanzee material culture. The chaîne opératoire conceptual framework, as introduced by ethnography, established technology as a phased process. Prehistoric archaeology adopted this concept to elucidate technological variability in tool-making procedures, based on knowledge of tool functions or subsistence patterns. We focused on the detection of operational sequences by wild chimpanzees (Pan troglodytes verus) when nut cracking with lithic implements at the sites of Bossou and Diecké, Guinea, West Africa. Thus, while it has recently been claimed that chimpanzees leave behind recognizable assemblages of stone hammers that can be morphologically distinguished from Oldowan hammers, this is the first study to focus specifically on the existence of operational sequences during the utilization of stone tools by wild chimpanzees. By combining primatological and archaeological methods and examining ecological areas inhabited by different chimpanzee groups, we sought technological variability and identified variables influencing regional diversity in tool typology and technology. We compared three case studies: (1) Bossou-direct recording of experimental nut-cracking sessions; (2) Bossou- direct and indirect monitoring of nut-cracking sites in the wild; (3) Diecké-indirect monitoring of nut-cracking sites in the wild. Results suggest that chimpanzees perform sequences of repeated tool transport and nut cracking. Data show discrimination of tool functions based on tool features. We identified the most technologically complex tool for nut cracking, which was composed of four stones. We found regional diversity in chimpanzee stone assemblages. Raw-material type and tool mobility constrain technological development in human and nonhuman primates. Spatial analysis of tool distribution indicates a pattern of resource-exploitation strategy, revealing affinities with Oldowan.

  5. DNA repair ability of cultured cells derived from mouse embryos in comparison with human cells

    International Nuclear Information System (INIS)

    Yaki, T.

    1982-01-01

    DNA repair in mouse cells derived from embryos of 3 inbred strains were investigated in comparison with that in human cells. The levels of unscheduled DNA synthesis after UV irradiation appeared to change at different passages, but capacities of host-cell reactivation of UV-irradiated herpes simplex virus were always reduced to the same levels as those in xeroderma pigmentosum cells. This implied that mouse cells are reduced in excision-repair capacities and that the apparently high levels of unscheduled DNA synthesis at certain passages are not quantitatively related to high levels of cell survival. Essentially no differences in DNA repair were noted among 3 strains - BALB/c, C3H/He and C57BL/10. (orig.)

  6. Spontaneous cross-species imitation in interactions between chimpanzees and zoo visitors.

    Science.gov (United States)

    Persson, Tomas; Sauciuc, Gabriela-Alina; Madsen, Elainie Alenkær

    2018-01-01

    Imitation is a cornerstone of human development, serving both a cognitive function (e.g. in the acquisition and transmission of skills and knowledge) and a social-communicative function, whereby the imitation of familiar actions serves to maintain social interaction and promote prosociality. In nonhuman primates, this latter function is poorly understood, or even claimed to be absent. In this observational study, we documented interactions between chimpanzees and zoo visitors and found that the two species imitated each other at a similar rate, corresponding to almost 10% of all produced actions. Imitation appeared to accomplish a social-communicative function, as cross-species interactions that contained imitative actions lasted significantly longer than interactions without imitation. In both species, physical proximity promoted cross-species imitation. Overall, imitative precision was higher among visitors than among chimpanzees, but this difference vanished in proximity contexts, i.e. in the indoor environment. Four of five chimpanzees produced imitations; three of them exhibited comparable imitation rates, despite large individual differences in level of cross-species interactivity. We also found that chimpanzees evidenced imitation recognition, yet only when visitors imitated their actions (as opposed to postures). Imitation recognition was expressed by returned imitation in 36% of the cases, and all four imitating chimpanzees engaged in so-called imitative games. Previously regarded as unique to early human socialization, such games serve to maintain social engagement. The results presented here indicate that nonhuman apes exhibit spontaneous imitation that can accomplish a communicative function. The study raises a number of novel questions for imitation research and highlights the imitation of familiar behaviours as a relevant-yet thus far understudied-research topic.

  7. Postnatal stem/progenitor cells derived from the dental pulp of adult chimpanzee

    Directory of Open Access Journals (Sweden)

    Fillos Dimitri

    2008-04-01

    Full Text Available Background Chimpanzee dental pulp stem/stromal cells (ChDPSCs are very similar to human bone marrow derived mesenchymal stem/stromal cells (hBMSCs as demonstrated by the expression pattern of cell surface markers and their multipotent differentiation capability. Results ChDPSCs were isolated from an incisor and a canine of a forty-seven year old female chimpanzee. A homogenous population of ChDPSCs was established in early culture at a high proliferation rate and verified by the expression pattern of thirteen cell surface markers. The ChDPSCs are multipotent and were capable of differentiating into osteogenic, adipogenic and chondrogenic lineages under appropriate in vitro culture conditions. ChDPSCs also express stem cell (Sox-2, Nanog, Rex-1, Oct-4 and osteogenic (Osteonectin, osteocalcin, osteopontin markers, which is comparable to reported results of rhesus monkey BMSCs (rBMSCs, hBMSCs and hDPSCs. Although ChDPSCs vigorously proliferated during the initial phase and gradually decreased in subsequent passages, the telomere length indicated that telomerase activity was not significantly reduced. Conclusion These results demonstrate that ChDPSCs can be efficiently isolated from post-mortem teeth of adult chimpanzees and are multipotent. Due to the almost identical genome composition of humans and chimpanzees, there is an emergent need for defining the new role of chimpanzee modeling in comparative medicine. Teeth are easy to recover at necropsy and easy to preserve prior to the retrieval of dental pulp for stem/stromal cells isolation. Therefore, the establishment of ChDPSCs would preserve and maximize the applications of such a unique and invaluable animal model, and could advance the understanding of cellular functions and differentiation control of adult stem cells in higher primates.

  8. Postnatal stem/progenitor cells derived from the dental pulp of adult chimpanzee.

    Science.gov (United States)

    Cheng, Pei-Hsun; Snyder, Brooke; Fillos, Dimitri; Ibegbu, Chris C; Huang, Anderson Hsien-Cheng; Chan, Anthony W S

    2008-04-22

    Chimpanzee dental pulp stem/stromal cells (ChDPSCs) are very similar to human bone marrow derived mesenchymal stem/stromal cells (hBMSCs) as demonstrated by the expression pattern of cell surface markers and their multipotent differentiation capability. ChDPSCs were isolated from an incisor and a canine of a forty-seven year old female chimpanzee. A homogenous population of ChDPSCs was established in early culture at a high proliferation rate and verified by the expression pattern of thirteen cell surface markers. The ChDPSCs are multipotent and were capable of differentiating into osteogenic, adipogenic and chondrogenic lineages under appropriate in vitro culture conditions. ChDPSCs also express stem cell (Sox-2, Nanog, Rex-1, Oct-4) and osteogenic (Osteonectin, osteocalcin, osteopontin) markers, which is comparable to reported results of rhesus monkey BMSCs (rBMSCs), hBMSCs and hDPSCs. Although ChDPSCs vigorously proliferated during the initial phase and gradually decreased in subsequent passages, the telomere length indicated that telomerase activity was not significantly reduced. These results demonstrate that ChDPSCs can be efficiently isolated from post-mortem teeth of adult chimpanzees and are multipotent. Due to the almost identical genome composition of humans and chimpanzees, there is an emergent need for defining the new role of chimpanzee modeling in comparative medicine. Teeth are easy to recover at necropsy and easy to preserve prior to the retrieval of dental pulp for stem/stromal cells isolation. Therefore, the establishment of ChDPSCs would preserve and maximize the applications of such a unique and invaluable animal model, and could advance the understanding of cellular functions and differentiation control of adult stem cells in higher primates.

  9. Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application.

    Science.gov (United States)

    Khantasup, Kannika; Chantima, Warangkana; Sangma, Chak; Poomputsa, Kanokwan; Dharakul, Tararaj

    2015-12-01

    Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3-D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma.

  10. Chimpanzee Adenovirus Vector Ebola Vaccine.

    Science.gov (United States)

    Ledgerwood, Julie E; DeZure, Adam D; Stanley, Daphne A; Coates, Emily E; Novik, Laura; Enama, Mary E; Berkowitz, Nina M; Hu, Zonghui; Joshi, Gyan; Ploquin, Aurélie; Sitar, Sandra; Gordon, Ingelise J; Plummer, Sarah A; Holman, LaSonji A; Hendel, Cynthia S; Yamshchikov, Galina; Roman, Francois; Nicosia, Alfredo; Colloca, Stefano; Cortese, Riccardo; Bailer, Robert T; Schwartz, Richard M; Roederer, Mario; Mascola, John R; Koup, Richard A; Sullivan, Nancy J; Graham, Barney S

    2017-03-09

    The unprecedented 2014 epidemic of Ebola virus disease (EVD) prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species, that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×10 10 particle units or 2×10 11 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 8 weeks after vaccination; in addition, longer-term vaccine durability was assessed at 48 weeks after vaccination. In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×10 11 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10 11 particle-unit dose than in the group that received the 2×10 10 particle-unit dose (geometric mean titer against the Zaire antigen at week 4, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2×10 11 particle-unit dose than among those who received the 2×10 10 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07) at week 4. Assessment of the durability of the antibody response showed that titers remained high at week 48, with the highest titers in those who received the 2×10 11 particle-unit dose. Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At

  11. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Gao, Xiugong; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-01-01

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds

  12. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-08-15

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.

  13. Generation and characterization of a human-mouse chimeric high-affinity antibody that detects the DYKDDDDK FLAG peptide.

    Science.gov (United States)

    Ikeda, Koki; Koga, Tomoaki; Sasaki, Fumiyuki; Ueno, Ayumi; Saeki, Kazuko; Okuno, Toshiaki; Yokomizo, Takehiko

    2017-05-13

    DYKDDDDK peptide (FLAG) is a useful tool for investigating the function and localization of proteins whose antibodies (Abs) are not available. We recently established a high-affinity monoclonal antibody (mAb) for FLAG (clone 2H8). The 2H8 Ab is highly sensitive for detecting FLAG-tagged proteins by flowcytometry and immunoprecipitation, but it can yield nonspecific signals in immunohistochemistry of mouse tissues because it is of mouse origin. In this study, we reduced nonspecific signals by generating a chimeric 2H8 Ab with Fc fragments derived from human immunoglobulin. We fused a 5' terminal cDNA fragments for the Fab region of 2H8 mAb with 3' terminal cDNA fragments for Fc region of human IgG1. We transfected both chimeric plasmids and purified the resulting human-mouse chimeric 2H8. The chimeric 2H8 Ab successfully detected FLAG-tagged proteins in flowcytometry with anti-human IgG secondary Ab with comparable sensitivity to 2H8 mAb. Importantly, chimeric 2H8 detected specific FLAG peptide signals without nonspecific signals in immunohistochemical analysis with mouse tissues. This human-mouse chimeric high-affinity anti-FLAG Ab will prove useful for future immunohistochemical analysis of mouse tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Derivation of mouse embryonic stem cell lines from tyrosine hydroxylase reporter mice crossed with a human SNCA transgenic mouse model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Margarita Chumarina

    2017-03-01

    Full Text Available Mouse embryonic stem cell (mESC lines were derived by crossing heterozygous transgenic (tg mice expressing green fluorescent protein (GFP under the control of the rat tyrosine hydroxylase (TH promoter, with homozygous alpha-synuclein (aSYN mice expressing human mutant SNCAA53T under the control of the mouse Prion promoter (MoPrP, or wildtype (WT mice. The expression of GFP and human aSYN was validated by immunocytochemistry in midbrain neuron cultures upon differentiation of mESC lines using stromal cell-derived inducing activity. These mESC lines can help to study the impact of human aSYN expression in neurons and oligodendrocytes, and also trace GFP-expressing midbrain neurons.

  15. MetaPro-IQ: a universal metaproteomic approach to studying human and mouse gut microbiota.

    Science.gov (United States)

    Zhang, Xu; Ning, Zhibin; Mayne, Janice; Moore, Jasmine I; Li, Jennifer; Butcher, James; Deeke, Shelley Ann; Chen, Rui; Chiang, Cheng-Kang; Wen, Ming; Mack, David; Stintzi, Alain; Figeys, Daniel

    2016-06-24

    The gut microbiota has been shown to be closely associated with human health and disease. While next-generation sequencing can be readily used to profile the microbiota taxonomy and metabolic potential, metaproteomics is better suited for deciphering microbial biological activities. However, the application of gut metaproteomics has largely been limited due to the low efficiency of protein identification. Thus, a high-performance and easy-to-implement gut metaproteomic approach is required. In this study, we developed a high-performance and universal workflow for gut metaproteome identification and quantification (named MetaPro-IQ) by using the close-to-complete human or mouse gut microbial gene catalog as database and an iterative database search strategy. An average of 38 and 33 % of the acquired tandem mass spectrometry (MS) spectra was confidently identified for the studied mouse stool and human mucosal-luminal interface samples, respectively. In total, we accurately quantified 30,749 protein groups for the mouse metaproteome and 19,011 protein groups for the human metaproteome. Moreover, the MetaPro-IQ approach enabled comparable identifications with the matched metagenome database search strategy that is widely used but needs prior metagenomic sequencing. The response of gut microbiota to high-fat diet in mice was then assessed, which showed distinct metaproteome patterns for high-fat-fed mice and identified 849 proteins as significant responders to high-fat feeding in comparison to low-fat feeding. We present MetaPro-IQ, a metaproteomic approach for highly efficient intestinal microbial protein identification and quantification, which functions as a universal workflow for metaproteomic studies, and will thus facilitate the application of metaproteomics for better understanding the functions of gut microbiota in health and disease.

  16. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peng, H.; Armentano, D.; Mackenzie-Graham, L.; Shen, R.F.; Darlington, G.; Ledley, F.D.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (USA))

    1988-11-01

    Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients. The authors report development of a recombinant retrovirus based on the N2 vector for gene transfer and expression of human phenylalanine hydroxylase cDNA in primary mouse hepatocytes. This construct contains an internal promoter of the human {alpha}{sub 1}-antitrypsin gene driving transcription of the phenylalanine hydroxylase cDNA. Primary mouse hepatocytes were isolated from newborn mice, infected with the recombinant virus, and selected for expression of the neomycin-resistance gene. Hepatocytes transformed with the recombinant virus contained high levels of human phenylalanine hydroxylase mRNA transcripts originating from the retroviral and internal promoters. These results demonstrate that the transcriptional regulatory elements of the {alpha}{sub 1} antitrypsin gene retain their tissue-specific function in the recombinant provirus and establish a method for efficient transfer and high-level expression of human phenylalanine hydroxylase in primary hepatocytes.

  17. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes

    International Nuclear Information System (INIS)

    Peng, H.; Armentano, D.; Mackenzie-Graham, L.; Shen, R.F.; Darlington, G.; Ledley, F.D.; Woo, S.L.C.

    1988-01-01

    Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients. The authors report development of a recombinant retrovirus based on the N2 vector for gene transfer and expression of human phenylalanine hydroxylase cDNA in primary mouse hepatocytes. This construct contains an internal promoter of the human α 1 -antitrypsin gene driving transcription of the phenylalanine hydroxylase cDNA. Primary mouse hepatocytes were isolated from newborn mice, infected with the recombinant virus, and selected for expression of the neomycin-resistance gene. Hepatocytes transformed with the recombinant virus contained high levels of human phenylalanine hydroxylase mRNA transcripts originating from the retroviral and internal promoters. These results demonstrate that the transcriptional regulatory elements of the α 1 antitrypsin gene retain their tissue-specific function in the recombinant provirus and establish a method for efficient transfer and high-level expression of human phenylalanine hydroxylase in primary hepatocytes

  18. Zebrafish syntenic relationship to human/mouse genomes revealed by radiation hybrid mapping

    International Nuclear Information System (INIS)

    Samonte, Irene E.

    2007-01-01

    Zebrafish (Danio rerio) is an excellent model system for vertebrate developmental analysis and a new model for human disorders. In this study, however, zebrafish was used to determine its syntenic relationship to human/mouse genomes using the zebrafish-hamster radiation hybrid panel. The focus was on genes residing on chromosomes 6 and 17 of human and mouse, respectively, and some other genes of either immunologic or evolutionary importance. Gene sequences of interest and zebrafish expressed sequence tags deposited in the GenBank were used in identifying zebrafish homologs. Polymerase chain reaction (PCR) amplification, cloning and subcloning, sequencing, and phylogenetic analysis were done to confirm the homology of the candidate genes in zebrafish. The promising markers were then tested in the 94 zebrafish-hamster radiation hybrid panel cell lines and submitted for logarithm of the odds (LOD) score analysis to position genes on the zebrafish map. A total of 19 loci were successfully mapped to zebrafish linkage groups 1, 14, 15, 19, and 20. Four of these loci were positioned in linkage group 20, whereas, 3 more loci were added in linkage group 19, thus increasing to 34 loci the number of human genes syntenic to the group. With the sequencing of the zebrafish genome, about 20 more MHC genes were reported linked on the same group. (Author)

  19. Germ-line mutations at a mouse ESTR (Pc-3) locus and human microsatellite loci

    International Nuclear Information System (INIS)

    Ryo, Haruko; Nakajima, Hiroo; Nomura, Taisei

    2006-01-01

    We examined the use of the mouse Pc-3 ESTR (expanded simple tandem repeat) locus and 72 human microsatellite loci as potentially sensitive biomarkers for mutagenic exposures to germ cells in mice and humans respectively. In the mouse work, we treated male mice with TCDD (2, 3, 7, 8-tetrachlo-rodibenzo-p-dioxin; a chemical known to induce congenital anomalies in humans and mice) and, analysed the F 1 fetuses for Pc-3 mutations. Although the incidence of anomalies was higher in the TCDD group, there were no induced mutations. However, respiratory distress syndrome (RDS) was observed in 3 of 7 fetuses born to male mice which were treated with TCDD and which showed abnormal length of Pc-3 allele. In the human studies, the children of Chernobyl liquidators were examined for mutations at a total of 72 (31 autosomal, 1 X-linked and 40 Y-linked) microsatellite loci. This study was prompted by earlier findings of increases in microsatellite mutations in barn swallows and wheat in the highly contaminated areas after the Chernobyl accident. We examined 64 liquidator families (70 children) and 66 control families (70 children). However, no increases in mutation rates were found. The estimated mean dose to the liquidators was about 39 mSv and this might be one possible reason why no increases of mutations could be found. (author)

  20. Snakes as hazards: modelling risk by chasing chimpanzees.

    Science.gov (United States)

    McGrew, William C

    2015-04-01

    Snakes are presumed to be hazards to primates, including humans, by the snake detection hypothesis (Isbell in J Hum Evol 51:1-35, 2006; Isbell, The fruit, the tree, and the serpent. Why we see so well, 2009). Quantitative, systematic data to test this idea are lacking for the behavioural ecology of living great apes and human foragers. An alternative proxy is snakes encountered by primatologists seeking, tracking, and observing wild chimpanzees. We present 4 years of such data from Mt. Assirik, Senegal. We encountered 14 species of snakes a total of 142 times. Almost two-thirds of encounters were with venomous snakes. Encounters occurred most often in forest and least often in grassland, and more often in the dry season. The hypothesis seems to be supported, if frequency of encounter reflects selective risk of morbidity or mortality.

  1. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

    Science.gov (United States)

    Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

    2016-01-01

    There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.

  2. First GIS analysis of modern stone tools used by wild chimpanzees (Pan troglodytes verus in Bossou, Guinea, West Africa.

    Directory of Open Access Journals (Sweden)

    Alfonso Benito-Calvo

    Full Text Available Stone tool use by wild chimpanzees of West Africa offers a unique opportunity to explore the evolutionary roots of technology during human evolution. However, detailed analyses of chimpanzee stone artifacts are still lacking, thus precluding a comparison with the earliest archaeological record. This paper presents the first systematic study of stone tools used by wild chimpanzees to crack open nuts in Bossou (Guinea-Conakry, and applies pioneering analytical techniques to such artifacts. Automatic morphometric GIS classification enabled to create maps of use wear over the stone tools (anvils, hammers, and hammers/ anvils, which were blind tested with GIS spatial analysis of damage patterns identified visually. Our analysis shows that chimpanzee stone tool use wear can be systematized and specific damage patterns discerned, allowing to discriminate between active and passive pounders in lithic assemblages. In summary, our results demonstrate the heuristic potential of combined suites of GIS techniques for the analysis of battered artifacts, and have enabled creating a referential framework of analysis in which wild chimpanzee battered tools can for the first time be directly compared to the early archaeological record.

  3. First GIS analysis of modern stone tools used by wild chimpanzees (Pan troglodytes verus) in Bossou, Guinea, West Africa.

    Science.gov (United States)

    Benito-Calvo, Alfonso; Carvalho, Susana; Arroyo, Adrian; Matsuzawa, Tetsuro; de la Torre, Ignacio

    2015-01-01

    Stone tool use by wild chimpanzees of West Africa offers a unique opportunity to explore the evolutionary roots of technology during human evolution. However, detailed analyses of chimpanzee stone artifacts are still lacking, thus precluding a comparison with the earliest archaeological record. This paper presents the first systematic study of stone tools used by wild chimpanzees to crack open nuts in Bossou (Guinea-Conakry), and applies pioneering analytical techniques to such artifacts. Automatic morphometric GIS classification enabled to create maps of use wear over the stone tools (anvils, hammers, and hammers/ anvils), which were blind tested with GIS spatial analysis of damage patterns identified visually. Our analysis shows that chimpanzee stone tool use wear can be systematized and specific damage patterns discerned, allowing to discriminate between active and passive pounders in lithic assemblages. In summary, our results demonstrate the heuristic potential of combined suites of GIS techniques for the analysis of battered artifacts, and have enabled creating a referential framework of analysis in which wild chimpanzee battered tools can for the first time be directly compared to the early archaeological record.

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Mouse monoclonal antibodies against human c-Mpl and characterization for flow cytometry applications.

    Science.gov (United States)

    Abbott, Christina; Huang, Guo; Ellison, Aaron R; Chen, Ching; Arora, Taruna; Szilvassy, Stephen J; Wei, Ping

    2010-04-01

    Mouse monoclonal antibodies (MAbs) against human c-Mpl, the cognate receptor for thrombopoietin (TPO), were generated using hybridoma technology and characterized by various assays to demonstrate their specificity and affinity. Two such MAbs, 1.6 and 1.75, were determined to be superior for flow cytometry studies and exhibited double-digit picomolar (pM) affinities to soluble human c-Mpl protein. Both MAbs specifically bound to cells engineered to overexpress human c-Mpl protein, immortalized human hematopoietic cell lines that express endogenous c-Mpl, primary human bone marrow and peripheral blood-derived CD34(+) cells, and purified human platelets. No binding was detected on cell lines that did not express c-Mpl. Receptor competition and siRNA knock-down studies further confirmed the specificity of antibodies 1.6 and 1.75 for human c-Mpl. In contrast to these newly generated MAbs, none of eight commercially available anti-c-Mpl antibodies tested were found to bind specifically to human c-Mpl and were thus shown to be unsuitable for flow cytometry studies. Monoclonal antibodies 1.6 and 1.75 will therefore be useful flow cytometry reagents to detect cell surface c-Mpl expression.

  6. CpG methylation differences between neurons and glia are highly conserved from mouse to human.

    Science.gov (United States)

    Kessler, Noah J; Van Baak, Timothy E; Baker, Maria S; Laritsky, Eleonora; Coarfa, Cristian; Waterland, Robert A

    2016-01-15

    Understanding epigenetic differences that distinguish neurons and glia is of fundamental importance to the nascent field of neuroepigenetics. A recent study used genome-wide bisulfite sequencing to survey differences in DNA methylation between these two cell types, in both humans and mice. That study minimized the importance of cell type-specific differences in CpG methylation, claiming these are restricted to localized genomic regions, and instead emphasized that widespread and highly conserved differences in non-CpG methylation distinguish neurons and glia. We reanalyzed the data from that study and came to markedly different conclusions. In particular, we found widespread cell type-specific differences in CpG methylation, with a genome-wide tendency for neuronal CpG-hypermethylation punctuated by regions of glia-specific hypermethylation. Alarmingly, our analysis indicated that the majority of genes identified by the primary study as exhibiting cell type-specific CpG methylation differences were misclassified. To verify the accuracy of our analysis, we isolated neuronal and glial DNA from mouse cortex and performed quantitative bisulfite pyrosequencing at nine loci. The pyrosequencing results corroborated our analysis, without exception. Most interestingly, we found that gene-associated neuron vs. glia CpG methylation differences are highly conserved across human and mouse, and are very likely to be functional. In addition to underscoring the importance of independent verification to confirm the conclusions of genome-wide epigenetic analyses, our data indicate that CpG methylation plays a major role in neuroepigenetics, and that the mouse is likely an excellent model in which to study the role of DNA methylation in human neurodevelopment and disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. 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.

  8. Integration of a hand-reared chimpanzee (Pan troglodytes) infant into a social group of conspecifics.

    Science.gov (United States)

    Thunström, Maria; Persson, Tomas; Björklund, Mats

    2013-01-01

    Rejections of infants among non-human primates occasionally occur in the wild as well as in captive settings. Controlled adoptions of orphans and introductions of individuals into new groups are therefore sometimes necessary in captivity. Consequently, behavioral research on integration procedures and on the acceptance of infants by adoptive mothers is much needed. In this study, the introduction and subsequent adoption were examined in an 18-month-old hand-reared chimpanzee (Pan troglodytes). The infant was introduced into an age/sex-diversified social group of conspecifics at Furuvik Zoo, Gävle, Sweden, and continuous focal data was collected during the final stage of integration, including infant care exhibited by the group members and the infant's secure base behavior. The infant was successfully integrated into the group and engaged in positive social interactions with all group members. An adult primiparous female chimpanzee formed a bond resembling a mother-infant relationship with the infant, which continues to be maintained at publication. However, the female initially showed very limited interest in the infant. It was, in fact, two other younger female group members that exhibited most infant care. The infant's secure base behavior patterns indicate that she adapted well to the new circumstances in the chimpanzee group as the integration progressed. This provides evidence that a final adopter does not necessarily initially show maternal interest and that there can be flexibility in maternal behavior in adult chimpanzee females. Moreover, the methods applied employing gradual familiarization with all the group members and the use of an integration enclosure, may have contributed to a successful result. These findings extend our knowledge of introduction procedures in captivity as well as provide information on foster mother-infant attachment in chimpanzees.

  9. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    OpenAIRE

    Jiae Kim; Jiae Kim; Kristina K. Peachman; Kristina K. Peachman; Ousman Jobe; Ousman Jobe; Elaine B. Morrison; Atef Allam; Atef Allam; Linda Jagodzinski; Sofia A. Casares; Mangala Rao

    2017-01-01

    Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several...

  10. Contrasting features of urea cycle disorders in human patients and knockout mouse models.

    Science.gov (United States)

    Deignan, Joshua L; Cederbaum, Stephen D; Grody, Wayne W

    2008-01-01

    The urea cycle exists for the removal of excess nitrogen from the body. Six separate enzymes comprise the urea cycle, and a deficiency in any one of them causes a urea cycle disorder (UCD) in humans. Arginase is the only urea cycle enzyme with an alternate isoform, though no known human disorder currently exists due to a deficiency in the second isoform. While all of the UCDs usually present with hyperammonemia in the first few days to months of life, most disorders are distinguished by a characteristic profile of plasma amino acid alterations that can be utilized for diagnosis. While enzyme assay is possible, an analysis of the underlying mutation is preferable for an accurate diagnosis. Mouse models for each of the urea cycle disorders exist (with the exception of NAGS deficiency), and for almost all of them, their clinical and biochemical phenotypes rather closely resemble the phenotypes seen in human patients. Consequently, all of the current mouse models are highly useful for future research into novel pharmacological and dietary treatments and gene therapy protocols for the management of urea cycle disorders.

  11. Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18

    Directory of Open Access Journals (Sweden)

    Biliang Hu

    2017-09-01

    Full Text Available The effects of transgenically encoded human and mouse IL-18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR T cells are presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL-18R signaling. IL-18 augmented IFN-γ secretion and proliferation of T cells activated by the endogenous TCR. TCR-deficient, human IL-18-expressing CD19 CAR T cells exhibited enhanced proliferation and antitumor activity in the xenograft model. Antigen-propelled activation of cytokine helper ensemble (APACHE CAR T cells displayed inducible expression of IL-18 and enhanced antitumor immunity. In an intact mouse tumor model, CD19-IL-18 CAR T cells induced deeper B cell aplasia, significantly enhanced CAR T cell proliferation, and effectively augmented antitumor effects in mice with B16F10 melanoma. These findings point to a strategy to develop universal CAR T cells for patients with solid tumors.

  12. Genomic tools for evolution and conservation in the chimpanzee: Pan troglodytes ellioti is a genetically distinct population.

    Directory of Open Access Journals (Sweden)

    Rory Bowden

    Full Text Available In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10-20 is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions.

  13. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

    DEFF Research Database (Denmark)

    Sampaziotis, Fotios; Justin, Alexander W; Tysoe, Olivia C

    2017-01-01

    The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from....... The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs...

  14. Comparative analysis of protein coding sequences from human, mouse and the domesticated pig

    DEFF Research Database (Denmark)

    Jørgensen, Frank Grønlund; Hobolth, Asger; Hornshøj, Henrik

    2005-01-01

    Background: The availability of abundant sequence data from key model organisms has made large scale studies of mulecular evolution an exciting possibility. Here we use full length cDNA alignments comprising more than 700,000 nucleotides from human, mouse, pig and the Japanese pufferfish Fugu rub...... rubrices in order to investigate 1) the relationships between three major lineages of mammals: rodents, artiodactys and primates, and 2) the rate of evolution and the occurrence of positive Darwinian selection using codon based models of sequence evolution. Results: We provide evidence...

  15. The SCID-hu mouse and its application to human radiation biology

    International Nuclear Information System (INIS)

    Kyoizumi, Seishi; Akiyama, Mitoshi; McCune, J.M.; Namikawa, Reiko.

    1993-01-01

    The radiobiological study of humans has been hampered by a lack of suitable in vivo experimental models. Of course, acute and chronic radiation effects in humans have been documented in the studies of atomic bomb (A-bomb) survivors and patients irradiated either by therapeutic intent or by accident. However, the information gained from these studies has been limited by the difficulties in estimating precise radiation doses and in obtaining biological samples for directly analyzing the processes of radiation-induced pathogenesis. With these issues in mind, we propose that the severe combined immunodeficient mouse-human chimera can be used as an in vivo experimental model for human radiation biology. We have developed techniques by which normal human bone marrow can be implanted into immunodeficient C.B-17 scid/scid (SCID) mice (S. Kyoizumi et al, Blood 79, 1704, 1992). We have report that this in vivo model can be used for the analysis of radiation damage to human bone marrow. After whole-body irradiation of the engrafted animals, human progenitor cells within the human marrow were destroyed in a dose-dependent manner (D 0 = 0.7-1.0Gy, n = 1.0). Acute hematotoxicity was reduced when the radioprotective agent (WR-2721) was administered prior to irradiation. After low dose irradiation, the recovery of human progenitor activity was accelerated by treatment with human granulocyte-colony stimulating factor (G-CSF). This small animal model may prove amenable for the risk analysis of human radiation exposure as well as for the development of new modalities for the prevention and treatment of radiotoxic damage to the human hematopoietic system. (author)

  16. The importance of history in definitions of culture: Implications from phylogenetic approaches to the study of social learning in chimpanzees.

    Science.gov (United States)

    Lycett, Stephen J

    2010-08-01

    Some have claimed that wild chimpanzees possess multiple socially learned traditions that might constitute cultural patterns. Others, however, have suggested that even fundamental alternative explanations, such as proximate genetic mechanisms, have not been addressed satisfactorily. Multiple analyses using phylogenetic (cladistic) methods, however, have been shown not to support the genetic proposition. Rather, such analyses are more consistent with the growing body of evidence from studies of both wild and captive animals suggesting that behavioral patterns in wild chimpanzees are socially learned. The question remains, however, as to whether, from a scientific viewpoint, it is useful to term such patterns cultural. It is argued here that cultural mosaics of multiple behaviors that differ intercommunally, both in humans and chimpanzees, are an emergent property of a phylogenetic (i.e., historical) process of descent with modification, mediated by mechanisms of social transmission, variation, and sorting through time. This historical perspective is productive when attempting to consider the phenomenon of culture across species.

  17. Different early rearing experiences have long-term effects on cortical organization in captive chimpanzees (Pan troglodytes)

    DEFF Research Database (Denmark)

    Bogart, Stephanie L; Bennett, Allyson J; Schapiro, Steve

    2014-01-01

    -reared chimpanzees have greater global white-to-grey matter volume, more cortical folding and thinner grey matter within the cortical folds than nursery-reared animals. The findings reported here are the first to demonstrate that differences in early rearing conditions have significant consequences on brain......Consequences of rearing history in chimpanzees (Pan troglodytes) have been explored in relation to behavioral abnormalities and cognition; however, little is known about the effects of rearing conditions on anatomical brain development. Human studies have revealed that experiences of maltreatment...... and neglect during infancy and childhood can have detrimental effects on brain development and cognition. In this study, we evaluated the effects of early rearing experience on brain morphology in 92 captive chimpanzees (ages 11-43) who were either reared by their mothers (n = 46) or in a nursery (n = 46...

  18. Profound human/mouse differences in alpha-dystrobrevin isoforms: a novel syntrophin-binding site and promoter missing in mouse and rat

    Directory of Open Access Journals (Sweden)

    Jin Hong

    2009-12-01

    Full Text Available Abstract Background The dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin at the heart of the dystrophin glycoprotein complex in the main clinically affected tissues (skeletal muscle, heart and brain is its distant relative, α-dystrobrevin. The α-dystrobrevin gene is subject to complex transcriptional and post-transcriptional regulation, generating a substantial range of isoforms by alternative promoter use, alternative polyadenylation and alternative splicing. The choice of isoform is understood, amongst other things, to determine the stoichiometry of syntrophins (and their ligands in the dystrophin glycoprotein complex. Results We show here that, contrary to the literature, most α-dystrobrevin genes, including that of humans, encode three distinct syntrophin-binding sites, rather than two, resulting in a greatly enhanced isoform repertoire. We compare in detail the quantitative tissue-specific expression pattern of human and mouse α-dystrobrevin isoforms, and show that two major gene features (the novel syntrophin-binding site-encoding exon and the internal promoter and first exon of brain-specific isoforms α-dystrobrevin-4 and -5 are present in most mammals but specifically ablated in mouse and rat. Conclusion Lineage-specific mutations in the murids mean that the mouse brain has fewer than half of the α-dystrobrevin isoforms found in the human brain. Our finding that there are likely to be fundamental functional differences between the α-dystrobrevins (and therefore the dystrophin glycoprotein complexes of mice and humans raises questions about the current use of the mouse as the principal model animal for studying Duchenne muscular dystrophy and other related disorders, especially the neurological aspects thereof.

  19. A newborn infant chimpanzee snatched and cannibalized immediately after birth: Implications for "maternity leave" in wild chimpanzee.

    Science.gov (United States)

    Nishie, Hitonaru; Nakamura, Michio

    2018-01-01

    This study reports on the first observed case of a wild chimpanzee infant being snatched immediately after delivery and consequently cannibalized by an adult male in the Mahale Mountains, Tanzania. We demonstrate "maternity leave" from long-term data from the Mahale M group and suggest that it functions as a possible counterstrategy of mother chimpanzees against the risk of infanticide soon after delivery. The subjects of this study were the M group chimpanzees at Mahale Mountains, Tanzania. The case of cannibalism was observed on December 2, 2014. We used the long-term daily attendance record of the M group chimpanzees between 1990 and 2010 to calculate the lengths of "maternity leave," a perinatal period during which a mother chimpanzee tends to hide herself and gives birth alone. We observed a very rare case of delivery in a wild chimpanzee group. A female chimpanzee gave birth in front of other members, and an adult male snatched and cannibalized the newborn infant immediately after birth. Using the long-term data, we demonstrate that the length of "maternity leave" is longer than that of nonmaternity leave among adult and adolescent female chimpanzees. We argue that this cannibalism event immediately after birth occurred due to the complete lack of "maternity leave" of the mother chimpanzee of the victim, who might lack enough experience of delivery. We suggest that "maternity leave" taken by expecting mothers may function as a possible counterstrategy against infanticide soon after delivery. © 2017 Wiley Periodicals, Inc.

  20. Increased infectivity of anchorless mouse scrapie prions in transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Race, Brent; Phillips, Katie; Meade-White, Kimberly; Striebel, James; Chesebro, Bruce

    2015-06-01

    Prion protein (PrP) is found in all mammals, mostly as a glycoprotein anchored to the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) linkage. Following prion infection, host protease-sensitive prion protein (PrPsen or PrPC) is converted into an abnormal, disease-associated, protease-resistant form (PrPres). Biochemical characteristics, such as the PrP amino acid sequence, and posttranslational modifications, such as glycosylation and GPI anchoring, can affect the transmissibility of prions as well as the biochemical properties of the PrPres generated. Previous in vivo studies on the effects of GPI anchoring on prion infectivity have not examined cross-species transmission. In this study, we tested the effect of lack of GPI anchoring on a species barrier model using mice expressing human PrP. In this model, anchorless 22L prions derived from tg44 mice were more infectious than 22L prions derived from C57BL/10 mice when tested in tg66 transgenic mice, which expressed wild-type anchored human PrP at 8- to 16-fold above normal. Thus, the lack of the GPI anchor on the PrPres from tg44 mice appeared to reduce the effect of the mouse-human PrP species barrier. In contrast, neither source of prions induced disease in tgRM transgenic mice, which expressed human PrP at 2- to 4-fold above normal. Prion protein (PrP) is found in all mammals, usually attached to cells by an anchor molecule called GPI. Following prion infection, PrP is converted into a disease-associated form (PrPres). While most prion diseases are species specific, this finding is not consistent, and species barriers differ in strength. The amino acid sequence of PrP varies among species, and this variability affects prion species barriers. However, other PrP modifications, including glycosylation and GPI anchoring, may also influence cross-species infectivity. We studied the effect of PrP GPI anchoring using a mouse-to-human species barrier model. Experiments showed that prions produced by

  1. A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human.

    Science.gov (United States)

    Fennell, T R; Brown, C D

    2001-06-15

    Ethylene oxide (EO) is widely used as a gaseous sterilant and industrial intermediate and is a direct-acting mutagen and carcinogen. The objective of these studies was to develop physiologically based pharmacokinetic (PB-PK) models for EO to describe the exposure-tissue dose relationship in rodents and humans. We previously reported results describing in vitro and in vivo kinetics of EO metabolism in male and female F344 rats and B6C3F1 mice. These studies were extended by determining the kinetics of EO metabolism in human liver cytosol and microsomes. The results indicate enzymatically catalyzed GSH conjugation via cytosolic glutathione S-transferase (cGST) and hydrolysis via microsomal epoxide hydrolase (mEH) occur in both rodents and humans. The in vitro kinetic constants were scaled to account for cytosolic (cGST) and microsomal (mEH) protein content and incorporated into PB-PK descriptions for mouse, rat, and human. Flow-limited models adequately predicted blood and tissue EO levels, disposition, and elimination kinetics determined experimentally in rats and mice, with the exception of testis concentrations, which were overestimated. Incorporation of a diffusion-limited description for testis improved the ability of the model to describe testis concentrations. The model accounted for nonlinear increases in blood and tissue concentrations that occur in mice on exposure to EO concentrations greater than 200 ppm. Species differences are predicted in the metabolism and exposure-dose relationship, with a nonlinear relationship observed in the mouse as a result of GSH depletion. These models represent an essential step in developing a mechanistically based EO exposure-dose-response description for estimating human risk from exposure to EO. Copyright 2001 Academic Press.

  2. Regulation of homocysteine metabolism and methylation in human and mouse tissues

    Science.gov (United States)

    Chen, Natalie C.; Yang, Fan; Capecci, Louis M.; Gu, Ziyu; Schafer, Andrew I.; Durante, William; Yang, Xiao-Feng; Wang, Hong

    2010-01-01

    Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) metabolism involves multiple enzymes; however, tissue Hcy metabolism and its relevance to methylation remain unknown. Here, we established gene expression profiles of 8 Hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue cDNA libraries. We analyzed correlations between gene expression, Hcy, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM) levels, and SAM/SAH ratios in mouse tissues. Hcy metabolic and methylation enzymes were classified into two types. The expression of Type 1 enzymes positively correlated with tissue Hcy and SAH levels. These include cystathionine β-synthase, cystathionine-γ-lyase, paraxonase 1, 5,10-methylenetetrahydrofolate reductase, betaine:homocysteine methyltransferase, methionine adenosyltransferase, phosphatidylethanolamine N-methyltransferases and glycine N-methyltransferase. Type 2 enzyme expressions correlate with neither tissue Hcy nor SAH levels. These include SAH hydrolase, methionyl-tRNA synthase, 5-methyltetrahydrofolate:Hcy methyltransferase, S-adenosylmethionine decarboxylase, DNA methyltransferase 1/3a, isoprenylcysteine carboxyl methyltransferases, and histone-lysine N-methyltransferase. SAH is the only Hcy metabolite significantly correlated with Hcy levels and methylation enzyme expression. We established equations expressing combined effects of methylation enzymes on tissue SAH, SAM, and SAM/SAH ratios. Our study is the first to provide panoramic tissue gene expression profiles and mathematical models of tissue methylation regulation.—Chen, N. C., Yang, F., Capecci, L. M., Gu, Z., Schafer, A. I., Durante, W., Yang, X.-F., Wang, H. Regulation of homocysteine metabolism and methylation in human and mouse tissues. PMID:20305127

  3. Measuring Hair Cortisol Concentrations to Assess the Effect of Anthropogenic Impacts on Wild Chimpanzees (Pan troglodytes.

    Directory of Open Access Journals (Sweden)

    Esther H D Carlitz

    Full Text Available Non-human primates face major environmental changes due to increased human impacts all over the world. Although some species are able to survive in certain landscapes with anthropogenic impact, their long-term viability and fitness may be decreased due to chronic stress. Here we assessed long-term stress levels through cortisol analysis in chimpanzee hair obtained from sleeping nests in northwestern Uganda, in order to estimate welfare in the context of ecotourism, forest fragmentation with human-wildlife conflicts, and illegal logging with hunting activity (albeit not of primates, compared with a control without human contact or conflict. Concerning methodological issues, season [F(2,129 = 37.4, p < 0.0001, r2 = 0.18] and the age of nests [F(2,178 = 20.3, p < 0.0001, r2 = 0.11] significantly predicted hair cortisol concentrations (HCC. With regard to effects of anthropogenic impacts, our results neither showed elevation of HCC due to ecotourism, nor due to illegal logging compared to their control groups. We did, however, find significantly increased HCC in the fragment group compared to chimpanzees living in a nearby intact forest [F(1,88 = 5.0, p = 0.03, r2 = 0.20]. In conclusion, our results suggest that hair cortisol analysis is a powerful tool that can help understanding the impact of anthropogenic disturbances on chimpanzee well-being and could be applied to other great ape species.

  4. Measuring Hair Cortisol Concentrations to Assess the Effect of Anthropogenic Impacts on Wild Chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Carlitz, Esther H D; Miller, Robert; Kirschbaum, Clemens; Gao, Wei; Hänni, Daniel C; van Schaik, Carel P

    2016-01-01

    Non-human primates face major environmental changes due to increased human impacts all over the world. Although some species are able to survive in certain landscapes with anthropogenic impact, their long-term viability and fitness may be decreased due to chronic stress. Here we assessed long-term stress levels through cortisol analysis in chimpanzee hair obtained from sleeping nests in northwestern Uganda, in order to estimate welfare in the context of ecotourism, forest fragmentation with human-wildlife conflicts, and illegal logging with hunting activity (albeit not of primates), compared with a control without human contact or conflict. Concerning methodological issues, season [F(2,129) = 37.4, p < 0.0001, r2 = 0.18] and the age of nests [F(2,178) = 20.3, p < 0.0001, r2 = 0.11] significantly predicted hair cortisol concentrations (HCC). With regard to effects of anthropogenic impacts, our results neither showed elevation of HCC due to ecotourism, nor due to illegal logging compared to their control groups. We did, however, find significantly increased HCC in the fragment group compared to chimpanzees living in a nearby intact forest [F(1,88) = 5.0, p = 0.03, r2 = 0.20]. In conclusion, our results suggest that hair cortisol analysis is a powerful tool that can help understanding the impact of anthropogenic disturbances on chimpanzee well-being and could be applied to other great ape species.

  5. Genetic and 'cultural' similarity in wild chimpanzees.

    Science.gov (United States)

    Langergraber, Kevin E; Boesch, Christophe; Inoue, Eiji; Inoue-Murayama, Miho; Mitani, John C; Nishida, Toshisada; Pusey, Anne; Reynolds, Vernon; Schubert, Grit; Wrangham, Richard W; Wroblewski, Emily; Vigilant, Linda

    2011-02-07

    The question of whether animals possess 'cultures' or 'traditions' continues to generate widespread theoretical and empirical interest. Studies of wild chimpanzees have featured prominently in this discussion, as the dominant approach used to identify culture in wild animals was first applied to them. This procedure, the 'method of exclusion,' begins by documenting behavioural differences between groups and then infers the existence of culture by eliminating ecological explanations for their occurrence. The validity of this approach has been questioned because genetic differences between groups have not explicitly been ruled out as a factor contributing to between-group differences in behaviour. Here we investigate this issue directly by analysing genetic and behavioural data from nine groups of wild chimpanzees. We find that the overall levels of genetic and behavioural dissimilarity between groups are highly and statistically significantly correlated. Additional analyses show that only a very small number of behaviours vary between genetically similar groups, and that there is no obvious pattern as to which classes of behaviours (e.g. tool-use versus communicative) have a distribution that matches patterns of between-group genetic dissimilarity. These results indicate that genetic dissimilarity cannot be eliminated as playing a major role in generating group differences in chimpanzee behaviour.

  6. [Preparation and characterization of mouse polyclonal antibody against conserved region of human FOXO3].

    Science.gov (United States)

    Li, Lei; Lyu, Dan

    2017-06-01

    Objective To purify the recombinant protein specific to conserved region of forkhead box O3 (FOXO3) and prepare mouse anti-human FOXO3 polyclonal antibody. Methods The DNA fragment (aa290-472) encoding conserved domain of FOXO3 was amplified by PCR, and subsequently cloned into pET28a vector. Following transformation into E.coli BL21, the soluble fusion protein His-FOXO3 was induced by IPTG and purified by Ni-NTA affinity chromatography. The purified protein was used to immunize BALB/c mice to generate polyclonal antibody. The characteristics of the polyclonal antibody were assessed by ELISA, Western blotting and immunoprecipitation assays. Results We successfully prepared the expression vector pET28a-FOXO3 (aa290-472) and expressed the purified fusion protein in a soluble form. By immunizing mice with the fusion protein, we obtained anti-human FOXO3 polyclonal antibody. ELISA and Western blotting showed that the mouse antibody could recognize specifically the endogenous FOXO3 protein. Conclusion The polyclonal antibody against conserved domain of FOXO3 can identify the endogenous FOXO3 protein. It can be used to analyze the endogenous FOXO3 expression level.

  7. Humanized mouse models to study pathophysiology and treatment of HIV infection.

    Science.gov (United States)

    Masse-Ranson, Guillemette; Mouquet, Hugo; Di Santo, James P

    2018-03-01

    Immunodeficient mice that lack all lymphocyte subsets and have phagocytic cells that are tolerant of human cells can be stably xenografted with human hematopoietic stem cell as well as other human tissues (fetal liver and thymus) creating 'human immune system' (HIS) mice. HIS mice develop all major human lymphocyte classes (B, T, natural killer, and innate lymphoid cell) and their specialized subsets as well as a variety of myeloid cells (dendritic cell, monocytes, and macrophages) thereby providing a small animal model in which to interrogate human immune responses to infection. HIS mouse models have been successfully used to study several aspects of HIV-1 biology, including viral life cycle (entry, restriction, replication, and spread) as well as virus-induced immunopathology (CD4 T-cell depletion, immune activation, and mucosal inflammation). Recent work has shown that HIV reservoirs can be established in HIV-infected HIS mice after treatment with combinations of antiretroviral drugs thereby providing a model to test new approaches to eliminate latently infected cells. HIS mice provide cost-effective preclinical platform to assess combination immunotherapies that can target HIV reservoirs. Therapeutic strategies validated in HIS mice should be considered in designing the roadmap toward HIV 'cure'.

  8. Effect of human milk as a treatment for dry eye syndrome in a mouse model.

    Science.gov (United States)

    Diego, Jose L; Bidikov, Luke; Pedler, Michelle G; Kennedy, Jeffrey B; Quiroz-Mercado, Hugo; Gregory, Darren G; Petrash, J Mark; McCourt, Emily A

    Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies' efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES. The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy. Treatment with BAK reduced the mean corneal epithelial thickness from 36.77±0.64 μm in the control mice to 21.29±3.2 μm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2±2.5 μm) or fat-reduced milk (36.1±1.58 μm), outcomes that were similar to treatment with cyclosporine (38.52±2.47 μm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76±1.78 μm and 27.99±2.75 μm, respectively), as were solvents used in the extraction of nopal materials (26.53±1.46 μm for ethyl acetate, 21.59±5.87 μm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to

  9. Structural similarities and differences between the human and the mouse pancreas

    Science.gov (United States)

    Dolenšek, Jurij; Rupnik, Marjan Slak; Stožer, Andraž

    2015-01-01

    Mice remain the most studied animal model in pancreas research. Since the findings of this research are typically extrapolated to humans, it is important to understand both similarities and differences between the 2 species. Beside the apparent difference in size and macroscopic organization of the organ in the 2 species, there are a number of less evident and only recently described differences in organization of the acinar and ductal exocrine tissue, as well as in the distribution, composition, and architecture of the endocrine islets of Langerhans. Furthermore, the differences in arterial, venous, and lymphatic vessels, as well as innervation are potentially important. In this article, the structure of the human and the mouse pancreas, together with the similarities and differences between them are reviewed in detail in the light of conceivable repercussions for basic research and clinical application. PMID:26030186

  10. Chimpanzees prefer African and Indian music over silence.

    Science.gov (United States)

    Mingle, Morgan E; Eppley, Timothy M; Campbell, Matthew W; Hall, Katie; Horner, Victoria; de Waal, Frans B M

    2014-10-01

    [Correction Notice: An Erratum for this article was reported in Vol 40(4) of Journal of Experimental Psychology: Animal Learning and Cognition (see record 2014-35305-001). For the article, the below files were used to create the audio used in this study. The original West African akan and North Indian raga pieces were used in their entirety and the Japanese taiko piece was used from the 0:19 second mark through the end. The tempo of each piece was adjusted so that they maintained an identical base tempo of 90 beats per minute, then looped to create 40 minutes of continuous music. Additionally, the volume of the music was standardized at 50 dB so that the all music maintained the same average amplitude. All audio manipulations were completed using GarageBand © (Apple Inc.).] All primates have an ability to distinguish between temporal and melodic features of music, but unlike humans, in previous studies, nonhuman primates have not demonstrated a preference for music. However, previous research has not tested the wide range of acoustic parameters present in many different types of world music. The purpose of the present study is to determine the spontaneous preference of common chimpanzees (Pan troglodytes) for 3 acoustically contrasting types of world music: West African akan, North Indian raga, and Japanese taiko. Sixteen chimpanzees housed in 2 groups were exposed to 40 min of music from a speaker placed 1.5 m outside the fence of their outdoor enclosure; the proximity of each subject to the acoustic stimulus was recorded every 2 min. When compared with controls, subjects spent significantly more time in areas where the acoustic stimulus was loudest in African and Indian music conditions. This preference for African and Indian music could indicate homologies in acoustic preferences between nonhuman and human primates. .

  11. New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood.

    Directory of Open Access Journals (Sweden)

    Yasumitsu Fujie

    Full Text Available Induced pluripotent stem cells (iPSCs are potentially valuable cell sources for disease models and future therapeutic applications; however, inefficient generation and the presence of integrated transgenes remain as problems limiting their current use. Here, we developed a new Sendai virus vector, TS12KOS, which has improved efficiency, does not integrate into the cellular DNA, and can be easily eliminated. TS12KOS carries KLF4, OCT3/4, and SOX2 in a single vector and can easily generate iPSCs from human blood cells. Using TS12KOS, we established iPSC lines from chimpanzee blood, and used DNA array analysis to show that the global gene-expression pattern of chimpanzee iPSCs is similar to those of human embryonic stem cell and iPSC lines. These results demonstrated that our new vector is useful for generating iPSCs from the blood cells of both human and chimpanzee. In addition, the chimpanzee iPSCs are expected to facilitate unique studies into human physiology and disease.

  12. 78 FR 39741 - Announcement of Agency Decision: Recommendations on the Use of Chimpanzees in NIH-Supported Research

    Science.gov (United States)

    2013-07-02

    ..., chimpanzees have served an important role in advancing human health. However, new methods and technologies... behaviorists or veterinarians familiar with the animals. These commenters agreed on the importance of achieving... compliance-monitoring methods. We discuss the NIH's role in enforcing the accepted recommendations in the...

  13. Testing the social dog hypothesis: are dogs also more skilled than chimpanzees in non-communicative social tasks?

    Science.gov (United States)

    Wobber, Victoria; Hare, Brian

    2009-07-01

    Relative to non-human primates, domestic dogs possess a number of social skills that seem exceptional-particularly in solving problems involving cooperation and communication with humans. However, the degree to which dogs' unusual skills are contextually specialized is still unclear. Here, we presented dogs with a social problem that did not require them to use cooperative-communicative cues and compared their performance to that of chimpanzees to assess the extent of dogs' capabilities relative to those of non-human primates. We tested the abilities of dogs and chimpanzees to inhibit previously learned responses by using a social and a non-social version of a reversal learning task. In contrast to previous findings in cooperative-communicative social tasks, dogs were not more skilled on the social task than the non-social task, while chimpanzees were significantly better in the social paradigm. Chimpanzees were able to inhibit their prior learning better and more quickly in the social paradigm than they were in the non-social paradigm, while dogs took more time to inhibit what they had learned in both versions of the task. These results suggest that the dogs' sophisticated social skills in using human social cues may be relatively specialized as a result of domestication.

  14. Radiosensitivity and cell kinetics of the human solid cancer transplanted to nude mouse

    International Nuclear Information System (INIS)

    Ikeuchi, Shunji

    1983-01-01

    This study was undertaken to analyse the relationship between radiosensitivity and cell kinetics of human solid cancer in experimental nude mouse system. Four strains of tumors used for the experiment were poorly differentiated squamous cell carcinoma of the lung (Lu-9), oat cell carcinoma of the lung (Lu-24), well differentiated squamous cell carcinoma of the tongue (To-1) and moderately differentiated squamous cell carcinoma of the esophagus (Es-4) which were serially transplantable to BALB/c nude mice. Radiosensitivity was evaluated by tumor growth in terms of inhibition rate, histological change and host reaction after irradiation. Cell kinetics were studied by autoradiography with pulse administration of 3 H-thymidine to mice. Although Lu-24 was most radiosensitive, followed by To-1, Es-4 and Lu-9 in the order of sensitivity, it was suggested that they might be more radioresistant in nude mice without T-cell function than in human. Regarding squamous cell carcinomas, well differentiated type was more radiosensitive than poorly differentiated one. All of these tumors in nude mouse revealed distinct percent labeled mitosis curves with two clear peaks which were quite different from those in human body. Lu-24 showed a characteristic pattern with a long time lag before visible growth, short G 1 , and low growth fraction, compared to other three tumors. Three strains of squamous cell carcinoma demonstrated similar cell kinetic factors which were almost the same as those in human body reported previously. The differences in volume doubling time of tumor, growth fraction and cell loss factor were partially related to those of radiosensitivities among tumors except for Lu-24. The theoretical volume doubling time was proved to be most reliable for estimation of effectiveness of irradiation, but the labeling index was not a valuable indicator for it. (author)

  15. A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury

    Directory of Open Access Journals (Sweden)

    Samal Zhussupbekova

    2016-07-01

    Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

  16. Cognitive and physiological markers of emotional awareness in chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Parr, L A

    2001-11-01

    The ability to understand emotion in others is one of the most important factors involved in regulating social interactions in primates. Such emotional awareness functions to coordinate activity among group members, enable the formation of long-lasting individual relationships, and facilitate the pursuit of shared interests. Despite these important evolutionary implications, comparative studies of emotional processing in humans and great apes are practically nonexistent, constituting a major gap in our understanding of the extent to which emotional awareness has played an important role in shaping human behavior and societies. This paper presents the results of two experiments that examine chimpanzees' responses to emotional stimuli. First, changes in peripheral skin temperature were measured while subjects viewed three categories of emotionally negative video scenes; conspecifics being injected with needles (INJ), darts and needles alone (DART), and conspecific directing agonism towards the veterinarians (CHASE). Second, chimpanzees were required to use facial expressions to categorize emotional video scenes, i.e., favorite food and objects and veterinarian procedures, according to their positive and negative valence. With no prior training, subjects spontaneously matched the emotional videos to conspecific facial expressions according to their shared emotional meaning, indicating that chimpanzee facial expressions are processed emotionally, as are human expressions. Decreases in peripheral skin temperature, indicative of negative sympathetic arousal, were significantly lower when subjects viewed the INJ and DART videos, compared to the CHASE videos, indicating greater negative arousal when viewing conspecifics being injected with needles, and needles themselves, than when viewing conspecifics engaged in general agonism.

  17. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    Science.gov (United States)

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  18. Training a young Chimpanzee to attend to acoustic stimuli

    NARCIS (Netherlands)

    Bierens de Haan, J.A.

    1949-01-01

    For certain reasons I wished to train a young chimpanzee to choose from two similar boxes the one characterised by the ticking of a metronome inside it. My subject was a young male chimpanzee (Pan leucoprymnus Lesson), approximately three years old, Tommy by name. He was a good-natured chap, quite

  19. Chimpanzees in AIDS research: A biomedical and bioethical perspective.

    NARCIS (Netherlands)

    R. van den Akker (Ruud); M. Balls; J.W. Eichberg; J. Goodall; J.L. Heeney (Jonathan); A.D.M.E. Osterhaus (Albert); A.M. Prince; I. Spruit

    1993-01-01

    textabstractThe present article represents a consensus view of the appropriate utilization of chimpanzees in AIDS research arrived at as a result of a meeting of a group of scientists involved in AIDS research with chimpanzees and bioethicists. The paper considers which types of studies are

  20. Catalog of Differentially Expressed Long Non-Coding RNA following Activation of Human and Mouse Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Benoit T. Roux

    2017-08-01

    Full Text Available Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs are novel regulators of immunity, there has been no systematic attempt to identify and characterize the lncRNAs whose expression is changed following the induction of the innate immune response. To address this issue, we have employed next-generation sequencing data to determine the changes in the lncRNA profile in four human (monocytes, macrophages, epithelium, and chondrocytes and four mouse cell types (RAW 264.7 macrophages, bone marrow-derived macrophages, peritoneal macrophages, and splenic dendritic cells following exposure to the pro-inflammatory mediators, lipopolysaccharides (LPS, or interleukin-1β. We show differential expression of 204 human and 210 mouse lncRNAs, with positional analysis demonstrating correlation with immune-related genes. These lncRNAs are predominantly cell-type specific, composed of large regions of repeat sequences, and show poor evolutionary conservation. Comparison within the human and mouse sequences showed less than 1% sequence conservation, although we identified multiple conserved motifs. Of the 204 human lncRNAs, 21 overlapped with syntenic mouse lncRNAs, of which five were differentially expressed in both species. Among these syntenic lncRNA was IL7-AS (antisense, which was induced in multiple cell types and shown to regulate the production of the pro-inflammatory mediator interleukin-6 in both human and mouse cells. In summary, we have identified and characterized those lncRNAs that are differentially expressed following activation of the human and mouse innate immune responses and believe that these catalogs will provide the foundation for the future analysis of the role of lncRNAs in immune and inflammatory responses.

  1. Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex vivo.

    Science.gov (United States)

    De Silva, Samantha R; Charbel Issa, Peter; Singh, Mandeep S; Lipinski, Daniel M; Barnea-Cramer, Alona O; Walker, Nathan J; Barnard, Alun R; Hankins, Mark W; MacLaren, Robert E

    2016-11-01

    Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4 -/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4 -/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.

  2. Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

    Science.gov (United States)

    Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy; Ransick, Andrew; Suh, Gio; Guo, Jinjin; Kim, Albert D; Parvez, Riana K; Ruffins, Seth W; Rutledge, Elisabeth A; Thornton, Matthew E; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

    2018-06-04

    Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

    2007-01-01

    to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

  4. Reciprocal mouse and human limb phenotypes caused by gain- and loss-of-function mutations affecting Lmbr1.

    OpenAIRE

    Clark, R M; Marker, P C; Roessler, E; Dutra, A; Schimenti, J C; Muenke, M; Kingsley, D M

    2001-01-01

    The major locus for dominant preaxial polydactyly in humans has been mapped to 7q36. In mice the dominant Hemimelic extra toes (Hx) and Hammertoe (Hm) mutations map to a homologous chromosomal region and cause similar limb defects. The Lmbr1 gene is entirely within the small critical intervals recently defined for both the mouse and human mutations and is misexpressed at the exact time that the mouse Hx phenotype becomes apparent during limb development. This result suggests that Lmbr1 may un...

  5. Intramacrophage survival of uropathogenic Escherichia coli: Differences between diverse clinical isolates and between mouse and human macrophages

    DEFF Research Database (Denmark)

    Bokil, Nilesh J.; Totsika, Makrina; Carey, Alison J.

    2011-01-01

    assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50...... or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1+ vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data...

  6. Social comparison mediates chimpanzees' responses to loss, not frustration

    DEFF Research Database (Denmark)

    Hopper, Lydia M; Lambeth, Susan P; Schapiro, Steve

    2014-01-01

    Why do chimpanzees react when their partner gets a better deal than them? Do they note the inequity or do their responses reflect frustration in response to unattainable rewards? To tease apart inequity and contrast, we tested chimpanzees in a series of conditions that created loss through...... individual contrast, through inequity, or by both. Chimpanzees were tested in four social and two individual conditions in which they received food rewards in return for exchanging tokens with an experimenter. In conditions designed to create individual contrast, after completing an exchange, the chimpanzees...... were given a relatively less-preferred reward than the one they were previously shown. The chimpanzees' willingness to accept the less-preferred rewards was independent of previously offered foods in both the social and individual conditions. In conditions that created frustration through inequity...

  7. Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

    Directory of Open Access Journals (Sweden)

    Xinping Hao

    Full Text Available Age-related hearing loss (presbycusis is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old and aged (2-2.5 year-old mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the

  8. From forest to farm: systematic review of cultivar feeding by chimpanzees--management implications for wildlife in anthropogenic landscapes.

    Science.gov (United States)

    Hockings, Kimberley J; McLennan, Matthew R

    2012-01-01

    Crop-raiding is a major source of conflict between people and wildlife globally, impacting local livelihoods and impeding conservation. Conflict mitigation strategies that target problematic wildlife behaviours such as crop-raiding are notoriously difficult to develop for large-bodied, cognitively complex species. Many crop-raiders are generalist feeders. In more ecologically specialised species crop-type selection is not random and evidence-based management requires a good understanding of species' ecology and crop feeding habits. Comprehensive species-wide studies of crop consumption by endangered wildlife are lacking but are important for managing human-wildlife conflict. We conducted a comprehensive literature search of crop feeding records by wild chimpanzees (Pan troglodytes), a ripe-fruit specialist. We assessed quantitatively patterns of crop selection in relation to species-specific feeding behaviour, agricultural exposure, and crop availability. Crop consumption by chimpanzees is widespread in tropical Africa. Chimpanzees were recorded to eat a considerable range of cultivars (51 plant parts from 36 species). Crop part selection reflected a species-typical preference for fruit. Crops widely distributed in chimpanzee range countries were eaten at more sites than sparsely distributed crops. We identified 'high' and 'low' conflict crops according to their attractiveness to chimpanzees, taking account of their importance as cash crops and/or staple foods to people. Most (86%) high conflict crops were fruits, compared to 13% of low conflict crops. Some widely farmed cash or staple crops were seldom or never eaten by chimpanzees. Information about which crops are most frequently consumed and which are ignored has enormous potential for aiding on-the-ground stakeholders (i.e. farmers, wildlife managers, and conservation and agricultural extension practitioners) develop sustainable wildlife management schemes for ecologically specialised and protected species in

  9. The Metabolism of Separase Inhibitor Sepin-1 in Human, Mouse, and Rat Liver Microsomes

    Directory of Open Access Journals (Sweden)

    Feng Li

    2018-05-01

    Full Text Available Separase, a known oncogene, is widely overexpressed in numerous human tumors of breast, bone, brain, blood, and prostate. Separase is an emerging target for cancer therapy, and separase enzymatic inhibitors such as sepin-1 are currently being developed to treat separase-overexpressed tumors. Drug metabolism plays a critical role in the efficacy and safety of drug development, as well as possible drug–drug interactions. In this study, we investigated the in vitro metabolism of sepin-1 in human, mouse, and rat liver microsomes (RLM using metabolomic approaches. In human liver microsomes (HLM, we identified seven metabolites including one cysteine–sepin-1 adduct and one glutathione–sepin-1 adduct. All the sepin-1 metabolites in HLM were also found in both mouse and RLM. Using recombinant CYP450 isoenzymes, we demonstrated that multiple enzymes contributed to the metabolism of sepin-1, including CYP2D6 and CYP3A4 as the major metabolizing enzymes. Inhibitory effects of sepin-1 on seven major CYP450s were also evaluated using the corresponding substrates recommended by the US Food and Drug Administration. Our studies indicated that sepin-1 moderately inhibits CYP1A2, CYP2C19, and CYP3A4 with IC50 < 10 μM but weakly inhibits CYP2B6, CYP2C8/9, and CYP2D6 with IC50 > 10 μM. This information can be used to optimize the structures of sepin-1 for more suitable pharmacological properties and to predict the possible sepin-1 interactions with other chemotherapeutic drugs.

  10. Evaluation of Depigmenting Activity by 8-Hydroxydaidzein in Mouse B16 Melanoma Cells and Human Volunteers

    Directory of Open Access Journals (Sweden)

    Ching-Gong Lin

    2009-09-01

    Full Text Available In our previous study, 8-hydroxydaidzein (8-OHDe was demonstrated to be a potent and unique suicide substrate of mushroom tyrosinase. In this study, the compound was evaluated for in vitro cellular tyrosinase and melanogenesis inhibitory activities in mouse B16 melanoma cells and for in vivo skin-whitening activity in human volunteers. Tyrosinase activity and melanogenesis in the cell culture incubated with 10 µM of 8-OHDe were decreased to 20.1% and 51.8% of control, respectively, while no obvious cytotoxicity was observed in this concentration. In contrast, a standard tyrosinase inhibitor, kojic acid, showed 69.9% and 71.3% of control in cellular tyrosinase and melanogenesis activity, respectively, at a concentration as high as 100 µM. Hence, 8-OHDe exhibited more than an inhibitory effects on melanin production in B16 cells 10-fold stronger than kojic acid. In addition, when a cream containing 4% 8-OHDe was applied to human skin in an in vivo study, significant increases in the dL*-values were observed after three weeks. Moreover, the increase in the dL*-values after 8-week treatment with 4% 8-OHDe (from -0.57 to 1.94 is stronger than those of 2% 8-OHDe treatment (from 0.26 to 0.94 and 2% ascorbic acid-2-glucoside treatment (from 0.07 to 1.54. From the results of the study, it was concluded that 8-OHDe, the potent suicide substrate of mushroom tyrosinase, has depigmenting activities in both mouse melanoma cells and in human volunteers. Thus, the compound has significant potential for use in cosmetics as a skin-whitening ingredient.

  11. Foundations of cumulative culture in apes: improved foraging efficiency through relinquishing and combining witnessed behaviours in chimpanzees (Pan troglodytes).

    Science.gov (United States)

    Davis, Sarah J; Vale, Gillian L; Schapiro, Steven J; Lambeth, Susan P; Whiten, Andrew

    2016-10-24

    A vital prerequisite for cumulative culture, a phenomenon often asserted to be unique to humans, is the ability to modify behaviour and flexibly switch to more productive or efficient alternatives. Here, we first established an inefficient solution to a foraging task in five captive chimpanzee groups (N = 19). Three groups subsequently witnessed a conspecific using an alternative, more efficient, solution. When participants could successfully forage with their established behaviours, most individuals did not switch to this more efficient technique; however, when their foraging method became substantially less efficient, nine chimpanzees with socially-acquired information (four of whom witnessed additional human demonstrations) relinquished their old behaviour in favour of the more efficient one. Only a single chimpanzee in control groups, who had not witnessed a knowledgeable model, discovered this. Individuals who switched were later able to combine components of their two learned techniques to produce a more efficient solution than their extensively used, original foraging method. These results suggest that, although chimpanzees show a considerable degree of conservatism, they also have an ability to combine independent behaviours to produce efficient compound action sequences; one of the foundational abilities (or candidate mechanisms) for human cumulative culture.

  12. Genetic analysis of Enterobius vermicularis isolated from a chimpanzee with lethal hemorrhagic colitis and pathology of the associated lesions.

    Science.gov (United States)

    Yaguchi, Yuji; Okabayashi, Sachi; Abe, Niichiro; Masatou, Haruhisa; Iida, Shinya; Teramoto, Isao; Matsubayashi, Makoto; Shibahara, Tomoyuki

    2014-11-01

    Human pinworms, Enterobius vermicularis, are normally recognized as minor pathogens. However, a fatal case of human pinworm infection has been reported in a nonhuman primate, a zoo reared chimpanzee. Here, we histopathologically examined the lesions in tissues from the deceased chimpanzee and genetically characterized the isolated worms to investigate the pathogenicity and determine the phylogeny. We identified ulcers deep in the submucosa where many parasites were found to have invaded the lamina propria mucosa or submucous tissue. An inflammatory reaction consisting mainly of neutrophils and lymphocytes but not eosinophils was observed around the parasites, and intense hemorrhage in the lamina propria was confirmed. The parasites were morphologically similar to E. vermicularis based on the shape of the copulatory spicules. Mitochondrial cytochrome c oxidase subunit 1 gene products were amplified from worm DNA by PCR and were genetically identified as E. vermicularis based on >98.7% similarity of partial sequences. Phylogenetic analysis revealed that the sequences clustered together with other chimpanzee E. vermicularis isolates in a group which has been referred to as type C and which differs from human isolates (type A). The samples were negative for bacterial pathogens and Entamoeba histolytica indicating that E. vermicularis could be pathogenic in chimpanzees. Phylogenetic clustering of the isolates indicated that the parasite may be host specific.

  13. Chimpanzees, conflicts and cognition : The functions and mechanisms of chimpanzee conflict resolution

    NARCIS (Netherlands)

    Koski, S.E.

    2007-01-01

    In this thesis I studied conflict resolution in captive chimpanzees of the Arnhem Zoo, NL. Specifically, I investigated the occurrence and functions of various post-conflict strategies. Furthermore, I addressed the likely proximate cognitive and emotional mechanisms used in post-conflict

  14. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. The HIV-1 viral protein Tat increases glutamate and decreases GABA exocytosis from human and mouse neocortical nerve endings.

    Science.gov (United States)

    Musante, Veronica; Summa, Maria; Neri, Elisa; Puliti, Aldamaria; Godowicz, Tomasz T; Severi, Paolo; Battaglia, Giuseppe; Raiteri, Maurizio; Pittaluga, Anna

    2010-08-01

    Human immunodeficiency virus-1 (HIV-1)-encoded transactivator of transcription (Tat) potentiated the depolarization-evoked exocytosis of [(3)H]D-aspartate ([(3)H]D-ASP) from human neocortical terminals. The metabotropic glutamate (mGlu) 1 receptor antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) prevented this effect, whereas the mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) was ineffective. Western blot analysis showed that human neocortex synaptosomes possess mGlu1 and mGlu5 receptors. Tat potentiated the K(+)-evoked release of [(3)H]D-ASP or of endogenous glutamate from mouse neocortical synaptosomes in a CPCCOEt-sensitive and MPEP-insensitive manner. Deletion of mGlu1 receptors (crv4/crv4 mice) or mGlu5 receptors (mGlu5(-/-)mouse) silenced Tat effects. Tat enhanced inositol 1,4,5-trisphosphate production in human and mouse neocortical synaptosomes, consistent with the involvement of group I mGlu receptors. Tat inhibited the K(+)-evoked release of [(3)H]gamma-aminobutyric acid ([(3)H]GABA) from human synaptosomes and that of endogenous GABA or [(3)H]GABA from mouse nerve terminals; the inhibition was insensitive to CPCCOEt or MPEP. Tat-induced effects were retained by Tat(37-72) but not by Tat(48-85). In mouse neocortical slices, Tat facilitated the K(+)- and the veratridine-induced release of [(3)H]D-ASP in a CPCCOEt-sensitive manner and was ineffective in crv4/crv4 mouse slices. These observations are relevant to the comprehension of the pathophysiological effects of Tat in central nervous system and may suggest new potential therapeutic approaches to the cure of HIV-1-associated dementia.

  16. The immunomodulatory effects of shark cartilage on the mouse and human immune system

    Directory of Open Access Journals (Sweden)

    ali Sheikhian

    2007-01-01

    Materials and methods: In an experimental study, the effects of different doses of shark cartilage on humoral (antibody titer immune response against sheep red blood cells (SRBC, were measured in mouse. In addition, we evaluated the modulatory effects of the shark cartilage on the natural killer (NK activity of the peritoneal cells of mouse against a tumor cell line called K562, according to the standard methods. The proliferative response of the human peripheral blood mononuclear cells was measured under the influence of shark cartilage. Results: Pure shark cartilage enhanced antibody response against SRBC in vivo. The hemagglutination titer which was 1/147 in the control group (injected with hen cartilage, increased to 1/1355 in the test group. The optimal dose was 100 mg/ml. both type of cartilage had blastogenic effect on peripheral blood mononuclear cells (the blastogenic index was 6.7 and 4.9 for impure shark cartilage and hen cartilage, respectively. NK activity was inhibited completely by pure shark cartilage (the amount of the killing activity of the effector peritoneal cells for the control and test groups against target cells was 25.9% and 5.5% respectively. Conclusion: Shark cartilage has a potent immunomodulatory effect on the specific immune mechanisms and some inhibitory effects on the innate immune mechanisms such as NC activity. Since the specific immunity has a more pivotal role against tumor formation, shark cartilage can be used as a cancer immunotherapeutic.

  17. Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Marica Grskovic

    2007-08-01

    Full Text Available Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and identified genes upregulated in pluripotent cells both in vitro and in vivo. These genes are enriched for roles in transcription, chromatin remodeling, cell cycle, and DNA repair. We developed a novel computational algorithm, CompMoby, which combines analyses of sequences both aligned and non-aligned between different genomes with a probabilistic segmentation model to systematically predict short DNA motifs that regulate gene expression. CompMoby was used to identify conserved overrepresented motifs in genes upregulated in pluripotent cells. We show that the motifs are preferentially active in undifferentiated mouse ES and embryonic germ cells in a sequence-specific manner, and that they can act as enhancers in the context of an endogenous promoter. Importantly, the activity of the motifs is conserved in human ES cells. We further show that the transcription factor NF-Y specifically binds to one of the motifs, is differentially expressed during ES cell differentiation, and is required for ES cell proliferation. This study provides novel insights into the transcriptional regulatory networks of pluripotent cells. Our results suggest that this systematic approach can be broadly applied to understanding transcriptional networks in mammalian species.

  18. The effect of climate fluctuation on chimpanzee birth sex ratio.

    Directory of Open Access Journals (Sweden)

    Hjalmar S Kühl

    Full Text Available Climate and weather conditions, such as the North Atlantic Oscillation, precipitation and temperature influence the birth sex ratio (BSR of various higher latitude species, including deer, elephant seals or northern human populations. Although, tropical regions show only little variation in temperature, climate and weather conditions can fluctuate with consequences for phenology and food resource availability. Here, we evaluate, whether the BSR of chimpanzees, inhabiting African tropical forests, is affected by climate fluctuations as well. Additionally, we evaluate, if variation in consumption of a key food resource with high nutritional value, Coula edulis nuts, is linked to both climate fluctuations and variation in BSR. We use long-term data from two study groups located in Taï National Park, Côte d'Ivoire to assess the influence of local weather conditions and the global climate driver El Niño Southern Oscillation (ENSO on offspring sex. Côte d'Ivoire has experienced considerable climate variation over the last decades, with increasing temperature and declining precipitation. For both groups we find very similar time windows around the month of conception, in which offspring sex is well predicted by ENSO, with more males following low ENSO values, corresponding to periods of high rainfall. Furthermore, we find that the time spent cracking and feeding on Coula nuts is strongly influenced by climate conditions. Although, some of our analysis suggest that a higher proportion of males is born after periods with higher nut consumption frequency, we cannot conclude decisively at this point that nut consumption may influence shifts in BSR. All results combined suggest that also chimpanzees may experience climate related shifts in offspring sex ratios as response to climate fluctuation.

  19. Ingroup-outgroup bias in contagious yawning by chimpanzees supports link to empathy.

    Directory of Open Access Journals (Sweden)

    Matthew W Campbell

    2011-04-01

    Full Text Available Humans favor others seen as similar to themselves (ingroup over people seen as different (outgroup, even without explicitly stated bias. Ingroup-outgroup bias extends to involuntary responses, such as empathy for pain. However, empathy biases have not been tested in our close primate relatives. Contagious yawning has been theoretically and empirically linked to empathy. If empathy underlies contagious yawning, we predict that subjects should show an ingroup-outgroup bias by yawning more in response to watching ingroup members yawn than outgroup. Twenty-three chimpanzees (Pan troglodytes from two separate groups watched videos of familiar and unfamiliar individuals yawning or at rest (control. The chimpanzees yawned more when watching the familiar yawns than the familiar control or the unfamiliar yawns, demonstrating an ingroup-outgroup bias in contagious yawning. These results provide further empirical support that contagious yawning is a measure of empathy, which may be useful for evolutionary biology and mental health.

  20. Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease

    Science.gov (United States)

    Machado, Mariana Verdelho; Michelotti, Gregory Alexander; Xie, Guanhua; de Almeida, Thiago Pereira; Boursier, Jerome; Bohnic, Brittany; Guy, Cynthia D.; Diehl, Anna Mae

    2015-01-01

    Background and aims Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD) diet and Western diet. Methods Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose) for 16 weeks. Liver pathology and metabolic profile were compared. Results The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation) was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation. Conclusion Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH. PMID:26017539

  1. Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease.

    Directory of Open Access Journals (Sweden)

    Mariana Verdelho Machado

    Full Text Available Non-alcoholic steatohepatitis (NASH, the potentially progressive form of nonalcoholic fatty liver disease (NAFLD, is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD diet and Western diet.Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose for 16 weeks. Liver pathology and metabolic profile were compared.The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation.Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH.

  2. Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations

    Science.gov (United States)

    Yang, Tian; Jia, Zhonglin; Bryant-Pike, Whitney; Chandrasekhar, Anand; Murray, Jeffrey C; Fritzsch, Bernd; Bassuk, Alexander G

    2014-01-01

    Palate development is shaped by multiple molecular signaling pathways, including the Wnt pathway. In mice and humans, mutations in both the canonical and noncanonical arms of the Wnt pathway manifest as cleft palate, one of the most common human birth defects. Like the palate, numerous studies also link different Wnt signaling perturbations to varying degrees of limb malformation; for example, shortened limbs form in mutations of Ror2,Vangl2looptail and, in particular, Wnt5a. We recently showed the noncanonical Wnt/planar cell polarity (PCP) signaling molecule Prickle1 (Prickle like 1) also stunts limb growth in mice. We now expanded these studies to the palate and show that Prickle1 is also required for palate development, like Wnt5a and Ror2. Unlike in the limb, the Vangl2looptail mutation only aggravates palate defects caused by other mutations. We screened Filipino cleft palate patients and found PRICKLE1 variants, both common and rare, at an elevated frequency. Our results reveal that in mice and humans PRICKLE1 directs palate morphogenesis; our results also uncouple Prickle1 function from Vangl2 function. Together, these findings suggest mouse and human palate development is guided by PCP-Prickle1 signaling that is probably not downstream of Vangl2. PMID:24689077

  3. Chimpanzee pinworm, Enterobius anthropopitheci (Nematoda: Oxyuridae), maintained for more than twenty years in captive chimpanzees in Japan.

    Science.gov (United States)

    Hasegawa, Hideo; Udono, Toshifumi

    2007-08-01

    The chimpanzee pinworm, Enterobius anthropopitheci (Gedoelst, 1916), was found in chimpanzees, Pan troglodytes, reared in Kumamoto Primate Research Park, Sanwa Kagaku Kenkyusho Co., Ltd., Kumamoto, Japan, in 2006. Because the chimpanzees in this institution originated from chimpanzees imported from Africa before 1984, it is considered that E. anthropopitheci infection has persisted for more than 20 yr in the chimpanzees. Analysis of pinworm specimens preserved in the institution revealed that transition of predominant pinworm species occurred, responding to the change of anthelmintics used for pinworm treatment. Present dominance of E. anthropopitheci is surmised to be caused by fenbendazole, which has been adopted from 2002. Scarcity of mixed infection with E. anthropopitheci and Enterobius vermicularis suggests interspecific competition between the pinworms.

  4. Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

    Directory of Open Access Journals (Sweden)

    Dubal Dena B

    2012-11-01

    Full Text Available Abstract Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer’s – and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer’s disease (AD with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases.

  5. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    Science.gov (United States)

    Kim, Jiae; Peachman, Kristina K.; Jobe, Ousman; Morrison, Elaine B.; Allam, Atef; Jagodzinski, Linda; Casares, Sofia A.; Rao, Mangala

    2017-01-01

    Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4) molecule (DRAG mice) infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT)-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model for studying the

  6. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    Directory of Open Access Journals (Sweden)

    Jiae Kim

    2017-10-01

    Full Text Available Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP models for studying human immunodeficiency virus (HIV-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4 molecule (DRAG mice infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected