Science.gov

Sample records for apes

  1. Great Apes

    USGS Publications Warehouse

    Sleeman, Jonathan M.; Cerveny, Shannon

    2014-01-01

    Anesthesia of great apes is often necessary to conduct diagnostic analysis, provide therapeutics, facilitate surgical procedures, and enable transport and translocation for conservation purposes. Due to the stress of remote delivery injection of anesthetic agents, recent studies have focused on oral delivery and/or transmucosal absorption of preanesthetic and anesthetic agents. Maintenance of the airway and provision of oxygen is an important aspect of anesthesia in great ape species. The provision of analgesia is an important aspect of the anesthesia protocol for any procedure involving painful stimuli. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are often administered alone, or in combination to provide multi-modal analgesia. There is increasing conservation management of in situ great ape populations, which has resulted in the development of field anesthesia techniques for free-living great apes for the purposes of translocation, reintroduction into the wild, and clinical interventions.

  2. Aping our ancestors

    NASA Astrophysics Data System (ADS)

    Ennos, Roland

    2014-08-01

    Roland Ennos argues that the abilities of the great apes to cope in the dangerous mechanical environment of the forest canopy are part of the human species' intellectual inheritance and are intimately connected with our abilities as physicists.

  3. Lineage sorting in apes.

    PubMed

    Mailund, Thomas; Munch, Kasper; Schierup, Mikkel Heide

    2014-01-01

    Recombination allows different parts of the genome to have different genealogical histories. When a species splits in two, allelic lineages sort into the two descendant species, and this lineage sorting varies along the genome. If speciation events are close in time, the lineage sorting process may be incomplete at the second speciation event and lead to gene genealogies that do not match the species phylogeny. We review different recent approaches to model lineage sorting along the genome and show how it is possible to learn about population sizes, natural selection, and recombination rates in ancestral species from application of these models to genome alignments of great ape species.

  4. Darwin's apes and "savages".

    PubMed

    Martínez-Contreras, Jorge

    2010-02-01

    Since his visit to Tierra del Fuego in the 1830s, Darwin had been fascinated by the "savages" that succeeded in surviving on such a "broken beach", and because they were certainly similar in behaviour to our ancestors. However, he was also fascinated by baboons' behaviour, according to Brehm's accounts: hamadryas baboons showed a strong altruism to the point of risking their own lives in order to save their infants from attack by dogs. In 1871, he mentions he would rather have descended from brave baboons than from "savages", considered egoistic. We study the two sources of these ideas and try to show how Darwin's comparative reflections on apes and "savages" made him the first evolutionist anthropologist.

  5. Middle Miocene dispersals of apes.

    PubMed

    Andrews, Peter; Kelley, Jay

    2007-01-01

    The earliest record of fossil apes outside Africa is in the latest early Miocene of Turkey and eastern Europe. There were at least 2, and perhaps 4, species of ape, which were found associated with subtropical mixed environments of forest and more open woodland. Postcranial morphology is similar to that of early Miocene primates and indicates mainly generalized arboreal quadrupedal behaviours similar to those of less specialized New World monkeys such as Cebus. Robust jaws and thick enamelled teeth indicate a hard fruit diet. The 2 best known species of fossil ape are known from the site of Paşalar in Turkey. They have almost identical molar and jaw morphology. Molar morphology is also similar to that of specimens from Germany and Slovakia, but there are significant differences in the anterior teeth of the 2 Paşalar species. The more common species, Griphopithecus alpani, shares mainly primitive characters with early and middle Miocene apes in Africa, and it is most similar phenetically to Equatorius africanus from Maboko Island and Kipsaramon. The second species is assigned to a new species of Kenyapithecus, an African genus from Fort Ternan in Kenya, on the basis of a number of shared derived characters of the anterior dentition, and it is considered likely that there is a phylogenetic link between them. The African sites all date from the middle Miocene, similar in age to the Turkish and European ones, and the earliest emigration of apes from Africa coincides with the closure of the Tethys Sea preceding the Langhian transgression. Environments indicated for the African sites are mixtures of seasonal woodlands with some forest vegetation. The postcrania of both African taxa again indicate generalized arboreal adaptation but lacking specialized arboreal function. This middle Miocene radiation of both African and non-African apes was preceded by a radiation of arboreal catarrhine primates in the early Miocene, among which were the earliest apes. The earliest

  6. Ape gestures and language evolution

    PubMed Central

    Pollick, Amy S.; de Waal, Frans B. M.

    2007-01-01

    The natural communication of apes may hold clues about language origins, especially because apes frequently gesture with limbs and hands, a mode of communication thought to have been the starting point of human language evolution. The present study aimed to contrast brachiomanual gestures with orofacial movements and vocalizations in the natural communication of our closest primate relatives, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). We tested whether gesture is the more flexible form of communication by measuring the strength of association between signals and specific behavioral contexts, comparing groups of both the same and different ape species. Subjects were two captive bonobo groups, a total of 13 individuals, and two captive chimpanzee groups, a total of 34 individuals. The study distinguished 31 manual gestures and 18 facial/vocal signals. It was found that homologous facial/vocal displays were used very similarly by both ape species, yet the same did not apply to gestures. Both within and between species gesture usage varied enormously. Moreover, bonobos showed greater flexibility in this regard than chimpanzees and were also the only species in which multimodal communication (i.e., combinations of gestures and facial/vocal signals) added to behavioral impact on the recipient. PMID:17470779

  7. Rural School APE: Are We Breaking the Law?

    ERIC Educational Resources Information Center

    Benham-Deal, Tami

    1995-01-01

    A study of adapted physical education (APE) practices in rural Wyoming revealed that many school districts did not offer APE programs; minimal, if any, specialization was required of APE teachers; larger districts were more likely to employ APE teachers; and there was considerable need for APE teacher training. Contains survey questionnaire and…

  8. Rural School APE: Are We Breaking the Law?

    ERIC Educational Resources Information Center

    Benham-Deal, Tami

    1995-01-01

    A study of adapted physical education (APE) practices in rural Wyoming revealed that many school districts did not offer APE programs; minimal, if any, specialization was required of APE teachers; larger districts were more likely to employ APE teachers; and there was considerable need for APE teacher training. Contains survey questionnaire and…

  9. Comparative isotope ecology of African great apes.

    PubMed

    Oelze, Vicky M; Fahy, Geraldine; Hohmann, Gottfried; Robbins, Martha M; Leinert, Vera; Lee, Kevin; Eshuis, Henk; Seiler, Nicole; Wessling, Erin G; Head, Josephine; Boesch, Christophe; Kühl, Hjalmar S

    2016-12-01

    The isotope ecology of great apes is a useful reference for palaeodietary reconstructions in fossil hominins. As extant apes live in C3-dominated habitats, variation in isotope signatures is assumed to be low compared to hominoids exploiting C4-plant resources. However, isotopic differences between sites and between and within individuals are poorly understood due to the lack of vegetation baseline data. In this comparative study, we included all species of free-ranging African great apes (Pan troglodytes, Pan paniscus, Gorilla sp.). First, we explore differences in isotope baselines across different habitats and whether isotopic signatures in apes can be related to feeding niches (faunivory and folivory). Secondly, we illustrate how stable isotopic variations within African ape populations compare to other extant and extinct primates and discuss possible implications for dietary flexibility. Using 701 carbon and nitrogen isotope data points resulting from 148 sectioned hair samples and an additional collection of 189 fruit samples, we compare six different great ape sites. We investigate the relationship between vegetation baselines and climatic variables, and subsequently correct great ape isotope data to a standardized plant baseline from the respective sites. We obtained temporal isotopic profiles of individual animals by sectioning hair along its growth trajectory. Isotopic signatures of great apes differed between sites, mainly as vegetation isotope baselines were correlated with site-specific climatic conditions. We show that controlling for plant isotopic characteristics at a given site is essential for faunal data interpretation. While accounting for plant baseline effects, we found distinct isotopic profiles for each great ape population. Based on evidence from habituated groups and sympatric great ape species, these differences could possibly be related to faunivory and folivory. Dietary flexibility in apes varied, but temporal variation was overall

  10. Apes, Primitives, Children and...Translators.

    ERIC Educational Resources Information Center

    Kozulin, Alex

    1993-01-01

    Reviews two books by L. S. Vygotsky and A. R. Luria: (1) "Studies on the History of Behavior: Ape, Primitive, and Child"; and (2) "Ape, Primitive Man and Child: Essays in the History of Behavior." Both books are based on a book published in 1930 that examined the phylogenetic, historical, and ontogenetic development of human…

  11. Welfare of apes in captive environments: comments on, and by, a specific group of apes.

    PubMed

    Savage-Rumbaugh, Sue; Wamba, Kanzi; Wamba, Panbanisha; Wamba, Nyota

    2007-01-01

    Accurately determining the proper captive environment for apes requires adequately assessing the psychological similarities between apes and humans. Scientists currently believe apes lack mental complexity (Millikan, 2006), raising questions concerning the evolution of human culture from ape-like societies (Tomasello, 1999). A long-term cultural study with bonobos suggests less intellectual divergence from humans than currently postulated (Savage-Rumbaugh, 2005). Because humans view apes as mentally limited, some current captive environments may appear idyllic while offering only an illusion of appropriate care, derived from a simplistic view of what apes are, rather than what they might be. This perception of apes determines their handling, which determines their mental development, which perpetuates the prevailing perception. Only breaking this cycle will allow the current perception of apes to change. Their usual captive environment limits any demonstration of culture. However, the bonobo study reveals what ape culture can become, which should affect future welfare considerations for at least those species genetically close to humans (bonobos and chimpanzees). Development of a languaged bonobo culture allows these nonhuman animals to provide their own responses regarding adequate ape welfare.

  12. [The Great Ape Project--human rights for the great anthropoid apes].

    PubMed

    Scharmann, W

    2000-01-01

    The Great Ape Project (GAP) is an appeal of 36 scientist from different disciplines aiming at the legal equalisation of the non-human great apes (chimpanzees, gorillas and orang-utans) with man. The appeal is expressed by a number of essays stating zoological, genetical, ethological, anthropological, ethical and psychological knowledge and, based on these arguments, demanding the abolition of the species barrier between human beings and great apes. The central point of the initiative is the "Declaration on Great Apes", claiming the inclusion of great apes in the "community of equals" and thus securing three basic rights for all great apes: 1. The Right of Life; 2. The Protection of Individual Liberty; 3. The Prohibition of Torture. Not only experiments with great apes and their capture from the wilderness will be banned, but it is also intended to enfranchise as many great apes as possible from research laboratories and zoos. As a legal basis for the achievement of basic rights most of the authors plead for the idea of conferring the moral status of "persons" on great apes. Criticism of the GAP is due to its anthropocentrism. Rejection is especially expressed by advocates of pathocentric ethics who argue that the species barrier will not be abolished but only shifted, running then between the great apes and the remaining living beings. However, the GAP resulted in a greater retention in the use of great apes for experiments in several industrial countries. Additionally, the popular literature published by ethologists in the passed decades has supported a more responsible attitude of the public towards primates. Despite of all efforts the survival of the great apes is greatly endangered within their native countries.

  13. Apes in the Anthropocene: flexibility and survival.

    PubMed

    Hockings, Kimberley J; McLennan, Matthew R; Carvalho, Susana; Ancrenaz, Marc; Bobe, René; Byrne, Richard W; Dunbar, Robin I M; Matsuzawa, Tetsuro; McGrew, William C; Williamson, Elizabeth A; Wilson, Michael L; Wood, Bernard; Wrangham, Richard W; Hill, Catherine M

    2015-04-01

    We are in a new epoch, the Anthropocene, and research into our closest living relatives, the great apes, must keep pace with the rate that our species is driving change. While a goal of many studies is to understand how great apes behave in natural contexts, the impact of human activities must increasingly be taken into account. This is both a challenge and an opportunity, which can importantly inform research in three diverse fields: cognition, human evolution, and conservation. No long-term great ape research site is wholly unaffected by human influence, but research at those that are especially affected by human activity is particularly important for ensuring that our great ape kin survive the Anthropocene. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Great ape genetic diversity and population history.

    PubMed

    Prado-Martinez, Javier; Sudmant, Peter H; Kidd, Jeffrey M; Li, Heng; Kelley, Joanna L; Lorente-Galdos, Belen; Veeramah, Krishna R; Woerner, August E; O'Connor, Timothy D; Santpere, Gabriel; Cagan, Alexander; Theunert, Christoph; Casals, Ferran; Laayouni, Hafid; Munch, Kasper; Hobolth, Asger; Halager, Anders E; Malig, Maika; Hernandez-Rodriguez, Jessica; Hernando-Herraez, Irene; Prüfer, Kay; Pybus, Marc; Johnstone, Laurel; Lachmann, Michael; Alkan, Can; Twigg, Dorina; Petit, Natalia; Baker, Carl; Hormozdiari, Fereydoun; Fernandez-Callejo, Marcos; Dabad, Marc; Wilson, Michael L; Stevison, Laurie; Camprubí, Cristina; Carvalho, Tiago; Ruiz-Herrera, Aurora; Vives, Laura; Mele, Marta; Abello, Teresa; Kondova, Ivanela; Bontrop, Ronald E; Pusey, Anne; Lankester, Felix; Kiyang, John A; Bergl, Richard A; Lonsdorf, Elizabeth; Myers, Simon; Ventura, Mario; Gagneux, Pascal; Comas, David; Siegismund, Hans; Blanc, Julie; Agueda-Calpena, Lidia; Gut, Marta; Fulton, Lucinda; Tishkoff, Sarah A; Mullikin, James C; Wilson, Richard K; Gut, Ivo G; Gonder, Mary Katherine; Ryder, Oliver A; Hahn, Beatrice H; Navarro, Arcadi; Akey, Joshua M; Bertranpetit, Jaume; Reich, David; Mailund, Thomas; Schierup, Mikkel H; Hvilsom, Christina; Andrés, Aida M; Wall, Jeffrey D; Bustamante, Carlos D; Hammer, Michael F; Eichler, Evan E; Marques-Bonet, Tomas

    2013-07-25

    Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

  15. Apes produce tools for future use.

    PubMed

    Bräuer, Juliane; Call, Josep

    2015-03-01

    There is now growing evidence that some animal species are able to plan for the future. For example great apes save and exchange tools for future use. Here we raise the question whether chimpanzees, orangutans, and bonobos would produce tools for future use. Subjects only had access to a baited apparatus for a limited duration and therefore should use the time preceding this access to create the appropriate tools in order to get the rewards. The apes were tested in three conditions depending on the need for pre-prepared tools. Either eight tools, one tool or no tools were needed to retrieve the reward. The apes prepared tools in advance for future use and they produced them mainly in conditions when they were really needed. The fact that apes were able to solve this new task indicates that their planning skills are flexible. However, for the condition in which eight tools were needed, apes produced less than two tools per trial in advance. However, they used their chance to produce additional tools in the tool use phase-thus often obtaining most of the reward from the apparatus. Increased pressure to prepare more tools in advance did not have an effect on their performance. © 2014 Wiley Periodicals, Inc.

  16. Catastrophic ape decline in western equatorial Africa.

    PubMed

    Walsh, Peter D; Abernethy, Kate A; Bermejo, Magdalena; Beyers, Rene; De Wachter, Pauwel; Akou, Marc Ella; Huijbregts, Bas; Mambounga, Daniel Idiata; Toham, Andre Kamdem; Kilbourn, Annelisa M; Lahm, Sally A; Latour, Stefanie; Maisels, Fiona; Mbina, Christian; Mihindou, Yves; Obiang, Sosthène Ndong; Effa, Ernestine Ntsame; Starkey, Malcolm P; Telfer, Paul; Thibault, Marc; Tutin, Caroline E G; White, Lee J T; Wilkie, David S

    2003-04-10

    Because rapidly expanding human populations have devastated gorilla (Gorilla gorilla) and common chimpanzee (Pan troglodytes) habitats in East and West Africa, the relatively intact forests of western equatorial Africa have been viewed as the last stronghold of African apes. Gabon and the Republic of Congo alone are thought to hold roughly 80% of the world's gorillas and most of the common chimpanzees. Here we present survey results conservatively indicating that ape populations in Gabon declined by more than half between 1983 and 2000. The primary cause of the decline in ape numbers during this period was commercial hunting, facilitated by the rapid expansion of mechanized logging. Furthermore, Ebola haemorrhagic fever is currently spreading through ape populations in Gabon and Congo and now rivals hunting as a threat to apes. Gorillas and common chimpanzees should be elevated immediately to 'critically endangered' status. Without aggressive investments in law enforcement, protected area management and Ebola prevention, the next decade will see our closest relatives pushed to the brink of extinction.

  17. Rates and patterns of great ape retrotransposition.

    PubMed

    Hormozdiari, Fereydoun; Konkel, Miriam K; Prado-Martinez, Javier; Chiatante, Giorgia; Herraez, Irene Hernando; Walker, Jerilyn A; Nelson, Benjamin; Alkan, Can; Sudmant, Peter H; Huddleston, John; Catacchio, Claudia R; Ko, Arthur; Malig, Maika; Baker, Carl; Marques-Bonet, Tomas; Ventura, Mario; Batzer, Mark A; Eichler, Evan E

    2013-08-13

    We analyzed 83 fully sequenced great ape genomes for mobile element insertions, predicting a total of 49,452 fixed and polymorphic Alu and long interspersed element 1 (L1) insertions not present in the human reference assembly and assigning each retrotransposition event to a different time point during great ape evolution. We used these homoplasy-free markers to construct a mobile element insertions-based phylogeny of humans and great apes and demonstrate their differential power to discern ape subspecies and populations. Within this context, we find a good correlation between L1 diversity and single-nucleotide polymorphism heterozygosity (r(2) = 0.65) in contrast to Alu repeats, which show little correlation (r(2) = 0.07). We estimate that the "rate" of Alu retrotransposition has differed by a factor of 15-fold in these lineages. Humans, chimpanzees, and bonobos show the highest rates of Alu accumulation--the latter two since divergence 1.5 Mya. The L1 insertion rate, in contrast, has remained relatively constant, with rates differing by less than a factor of three. We conclude that Alu retrotransposition has been the most variable form of genetic variation during recent human-great ape evolution, with increases and decreases occurring over very short periods of evolutionary time.

  18. "An ape's view of the Oldowan" revisited.

    PubMed

    Wynn, Thomas; Hernandez-Aguilar, R Adriana; Marchant, Linda F; McGrew, William C

    2011-01-01

    In 1989, Wynn and McGrew published an explicit comparison between Oldowan technology and what was then known of chimpanzee technology. They compared the range and variety of tools, adaptive role of tools, carrying distances, spatial cognition, manufacturing procedures, and modes of learning. They concluded that everything archeologists had reconstructed about the behavior of Oldowan hominins could be accommodated within the ape adaptive grade; that is, a paraphyletic group united by overall similarities in anatomy and, in this case, behavior. The only Oldowan activities that were almost unknown for modern apes were the long-distance transport of objects and direct competition with carnivores, which was implied by meat acquisition activities. "In its general features Oldowan culture was ape, not human. Nowhere in this picture need we posit elements such as language, extensive sharing, division of labor, or pair-bonded families, all of which are part of the baggage carried by the term human."

  19. The Y chromosomes of the great apes.

    PubMed

    Hallast, Pille; Jobling, Mark A

    2017-05-01

    The great apes (orangutans, gorillas, chimpanzees, bonobos and humans) descended from a common ancestor around 13 million years ago, and since then their sex chromosomes have followed very different evolutionary paths. While great-ape X chromosomes are highly conserved, their Y chromosomes, reflecting the general lability and degeneration of this male-specific part of the genome since its early mammalian origin, have evolved rapidly both between and within species. Understanding great-ape Y chromosome structure, gene content and diversity would provide a valuable evolutionary context for the human Y, and would also illuminate sex-biased behaviours, and the effects of the evolutionary pressures exerted by different mating strategies on this male-specific part of the genome. High-quality Y-chromosome sequences are available for human and chimpanzee (and low-quality for gorilla). The chromosomes differ in size, sequence organisation and content, and while retaining a relatively stable set of ancestral single-copy genes, show considerable variation in content and copy number of ampliconic multi-copy genes. Studies of Y-chromosome diversity in other great apes are relatively undeveloped compared to those in humans, but have nevertheless provided insights into speciation, dispersal, and mating patterns. Future studies, including data from larger sample sizes of wild-born and geographically well-defined individuals, and full Y-chromosome sequences from bonobos, gorillas and orangutans, promise to further our understanding of population histories, male-biased behaviours, mutation processes, and the functions of Y-chromosomal genes.

  20. Cytogenetic studies of small ape (Hylobatidae) chromosomes.

    PubMed

    Stanyon, R

    2013-01-01

    Each genus of small apes has a highly distinctive karyotype (karyomorph) at every level of cytogenetic analysis. Early workers using classical staining and banding had problems integrating the karyolocial data with that of other primates. Chromosome painting allowed syntenic homology maps to be constructed for each of the four karyomorphs (2n = 38, 44, 50 and 52). They revealed that the great apes and Old World monkeys had strongly conserved karyotypes while those of small apes were highly rearranged. However, they provided contradictory phylogenetic results to other bio-molecular tree of small ape evolution. More recently BAC-FISH investigations using a panel of about 900 BACs defined each breakpoint by spanning or flanking BAC clones The syntenic map was refined and now includes small segments of homology which had previously gone undected, marker order (synteny block orientation) and the location of ancestral and Evolutionarily New Centromeres. However, the BAC-FISH data similar to other biomolecular methods used up to now could not resolve the phylogenetic tree of hylobatids. These difficulties may be explained by the rapid divergence of crown hylobatids, reticulate evolution and incomplete lineage sorting. The lack of significant cytogenetic landmarks at the nodes of the gibbon tree could indicate that chromosomal rearrangements did not play a primary role in hylobatid speciation.

  1. Apollo Photograph Evaluation (APE) programming manual

    NASA Technical Reports Server (NTRS)

    Kim, I. J.

    1974-01-01

    This document describes the programming techniques used to implement the equations of the Apollo Photograph Evaluation (APE) program on the UNIVAC 1108 computer and contains detailed descriptions of the program structure, a User's Guide section to provide the necessary information for proper operation of the program, and information for the assessment of the program's adaptability to future problems.

  2. The apeE Gene of Salmonella typhimurium Encodes an Outer Membrane Esterase Not Present in Escherichia coli

    PubMed Central

    Carinato, Maria E.; Collin-Osdoby, Patricia; Yang, Xioming; Knox, Tina M.; Conlin, Christopher A.; Miller, Charles G.

    1998-01-01

    Salmonella typhimurium apeR mutations lead to overproduction of an outer membrane-associated N-acetyl phenylalanine β-naphthyl ester-cleaving esterase that is encoded by the apeE gene (P. Collin-Osdoby and C. G. Miller, Mol. Gen. Genet. 243:674–680, 1994). This paper reports the cloning and nucleotide sequencing of the S. typhimurium apeE gene as well as some properties of the esterase that it encodes. The predicted product of apeE is a 69.9-kDa protein which is processed to a 67-kDa species by removal of a signal peptide. The predicted amino acid sequence of ApeE indicates that it is a member of the GDSL family of serine esterases/lipases. It is most similar to a lipase excreted by the entomopathogenic bacterium Photorhabdus luminescens. The Salmonella esterase catalyzes the hydrolysis of a variety of fatty acid naphthyl esters and of C6 to C16 fatty acid p-nitrophenyl esters but will not hydrolyze peptide bonds. A rapid diagnostic test reported to be useful in distinguishing Salmonella spp. from related organisms makes use of the ability of Salmonella to hydrolyze the chromogenic ester substrate methyl umbelliferyl caprylate. We report that the apeE gene product is the enzyme in Salmonella uniquely responsible for the hydrolysis of this substrate. Southern blot analysis indicates that Escherichia coli K-12 does not contain a close analog of apeE, and it appears that the apeE gene is contained in a region of DNA present in Salmonella but not in E. coli. PMID:9657991

  3. Ebolavirus Vaccines for Humans and Apes

    PubMed Central

    Fausther-Bovendo, Hugues; Mulangu, Sabue

    2012-01-01

    Due to high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. PMID:22560007

  4. Ebolavirus vaccines for humans and apes.

    PubMed

    Fausther-Bovendo, Hugues; Mulangu, Sabue; Sullivan, Nancy J

    2012-06-01

    Because of high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. Published by Elsevier B.V.

  5. How great is great ape foresight?

    PubMed

    Suddendorf, Thomas; Corballis, Michael C; Collier-Baker, Emma

    2009-09-01

    Osvath and Osvath (Anim Cogn 11: 661-674, 2008) report innovative studies with two chimpanzees and one orangutan that suggest some capacity to select and keep a tool for use about an hour later. This is a welcome contribution to a small, but rapidly growing, field. Here we point out some of the weaknesses in the current data and caution the interpretation the authors advance. It is not clear to what extent the apes really engaged in any foresight in these studies.

  6. Sequential tool use in great apes.

    PubMed

    Martin-Ordas, Gema; Schumacher, Lena; Call, Josep

    2012-01-01

    Sequential tool use is defined as using a tool to obtain another non-food object which subsequently itself will serve as a tool to act upon a further (sub)goal. Previous studies have shown that birds and great apes succeed in such tasks. However, the inclusion of a training phase for each of the sequential steps and the low cost associated with retrieving the longest tools limits the scope of the conclusions. The goal of the experiments presented here was, first to replicate a previous study on sequential tool use conducted on New Caledonian crows and, second, extend this work by increasing the cost of retrieving a tool in order to test tool selectivity of apes. In Experiment 1, we presented chimpanzees, orangutans and bonobos with an out-of-reach reward, two tools that were available but too short to reach the food and four out-of-reach tools differing in functionality. Similar to crows, apes spontaneously used up to 3 tools in sequence to get the reward and also showed a strong preference for the longest out-of reach tool independently of the distance of the food. In Experiment 2, we increased the cost of reaching for the longest out-of reach tool. Now apes used up to 5 tools in sequence to get the reward and became more selective in their choice of the longest tool as the costs of its retrieval increased. The findings of the studies presented here contribute to the growing body of comparative research on tool use.

  7. Moral reasoning about great apes in research

    NASA Astrophysics Data System (ADS)

    Okamoto, Carol Midori

    2006-04-01

    This study explored how individuals (biomedical scientists, Great Ape Project activists, lay adults, undergraduate biology and environmental studies students, and Grade 12 and 9 biology students) morally judge and reason about using great apes in biomedical and language research. How these groups perceived great apes' mental capacities (e.g., pain, logical thinking) and how these perceptions related to their judgments were investigated through two scenarios. In addition, the kinds of informational statements (e.g., biology, economics) that may affect individuals' scenario judgments were investigated. A negative correlation was found between mental attributions and scenario judgments while no clear pattern occurred for the informational statements. For the biomedical scenario, all groups significantly differed in mean judgment ratings except for the biomedical scientists, GAP activists and Grade 9 students. For the language scenario, all groups differed except for the GAP activists, and undergraduate environmental studies and Grade 9 students. An in-depth qualitative analysis showed that although the biomedical scientists, GAP activists and Grade 9 students had similar judgments, they produced different mean percentages of justifications under four moral frameworks (virtue, utilitarianism, deontology, and welfare). The GAP activists used more virtue reasoning while the biomedical scientists and Grade 9 students used more utilitarian and welfare reasoning, respectively. The results are discussed in terms of developing environmental/humane education curricula.

  8. Why are there apes? Evidence for the co-evolution of ape and monkey ecomorphology.

    PubMed

    Hunt, Kevin D

    2016-04-01

    Apes, members of the superfamily Hominoidea, possess a distinctive suite of anatomical and behavioral characters which appear to have evolved relatively late and relatively independently. The timing of paleontological events, extant cercopithecine and hominoid ecomorphology and other evidence suggests that many distinctive ape features evolved to facilitate harvesting ripe fruits among compliant terminal branches in tree edges. Precarious, unpredictably oriented, compliant supports in the canopy periphery require apes to maneuver using suspensory and non-sterotypical postures (i.e. postures with eccentric limb orientations or extreme joint excursions). Diet differences among extant species, extant species numbers and evidence of cercopithecoid diversification and expansion, in concert with a reciprocal decrease in hominoid species, suggest intense competition between monkeys and apes over the last 20 Ma. It may be that larger body masses allow great apes to succeed in contest competitions for highly desired food items, while the ability of monkeys to digest antifeedant-rich unripe fruits allows them to win scramble competitions. Evolutionary trends in morphology and inferred ecology suggest that as monkeys evolved to harvest fruit ever earlier in the fruiting cycle they broadened their niche to encompass first more fibrous, tannin- and toxin-rich unripe fruits and later, for some lineages, mature leaves. Early depletion of unripe fruit in the central core of the tree canopy by monkeys leaves a hollow sphere of ripening fruits, displacing antifeedant-intolerant, later-arriving apes to small-diameter, compliant terminal branches. Hylobatids, orangutans, Pan species, gorillas and the New World atelines may have each evolved suspensory behavior independently in response to local competition from an expanding population of monkeys. Genetic evidence of rapid evolution among chimpanzees suggests that adaptations to suspensory behavior, vertical climbing, knuckle

  9. The cognitive underpinnings of flexible tool use in great apes.

    PubMed

    Völter, Christoph J; Call, Josep

    2014-07-01

    Nonhuman primates perform poorly in trap tasks, a benchmark test of causal knowledge in nonhuman animals. However, recent evidence suggests that when the confound of tool use is avoided, great apes' performance improves dramatically. In the present study, we examined the cognitive underpinnings of tool use that contribute to apes' poor performance in trap tasks. We presented chimpanzees (Pan troglodytes), bonobos (Pan paniscus), and orangutans (Pongo abelii) with different versions of a maze-like multilevel trap task. We manipulated whether the apes had to use their fingers or a stick to negotiate a reward through the maze. Furthermore, we varied whether the apes obtained visual information about the functionality of the traps (i.e., blockage of free passage) or only arbitrary color stimuli indicating the location of the traps. We found that (a) apes in the finger-maze task outperformed apes in the tool-use-maze task (and partially planned their moves multiple steps ahead), and (b) tool-using apes failed to learn to avoid the traps and performed similar to apes that did not obtain functional information about the traps. Follow-up experiments with apes that already learned to avoid the traps showed that tool use or the color cues per se did not pose a problem for experienced apes. These results suggest that simultaneously monitoring 2 spatial relations (the tool-reward and reward-surface relation) might overstrain apes' cognitive system. Thus, trap tasks involving tool use might constitute a dual task loading on the same cognitive resources; a candidate for these shared resources is the attentional system.

  10. Ape malaria transmission and potential for ape-to-human transfers in Africa

    PubMed Central

    Makanga, Boris; Yangari, Patrick; Rahola, Nil; Rougeron, Virginie; Elguero, Eric; Boundenga, Larson; Moukodoum, Nancy Diamella; Okouga, Alain Prince; Arnathau, Céline; Durand, Patrick; Willaume, Eric; Ayala, Diego; Fontenille, Didier; Ayala, Francisco J.; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck; Paupy, Christophe

    2016-01-01

    Recent studies have highlighted the large diversity of malaria parasites infecting African great apes (subgenus Laverania) and their strong host specificity. Although the existence of genetic incompatibilities preventing the cross-species transfer may explain host specificity, the existence of vectors with a high preference for a determined host represents another possibility. To test this hypothesis, we undertook a 15-mo-long longitudinal entomological survey in two forest regions of Gabon, where wild apes live, at different heights under the canopy. More than 2,400 anopheline mosquitoes belonging to 18 species were collected. Among them, only three species of Anopheles were found infected with ape Plasmodium: Anopheles vinckei, Anopheles moucheti, and Anopheles marshallii. Their role in transmission was confirmed by the detection of the parasites in their salivary glands. Among these species, An. vinckei showed significantly the highest prevalence of infection and was shown to be able to transmit parasites of both chimpanzees and gorillas. Transmission was also shown to be conditioned by seasonal factors and by the heights of capture under the canopy. Moreover, human landing catches of sylvan Anopheles demonstrated the propensity of these three vector species to feed on humans when available. Our results suggest therefore that the strong host specificity observed in the Laveranias is not linked to a specific association between the vertebrate host and the vector species and highlight the potential role of these vectors as bridge between apes and humans. PMID:27071123

  11. Spatial cognition in apes and humans.

    PubMed

    Gentner, Dedre

    2007-05-01

    The debate on whether language influences cognition is sometimes seen as a simple dichotomy: cognitive development is governed either by innate predispositions or by influences of language and culture. In two recent papers on spatial cognition, Haun and colleagues break new ground in bringing together a comparative cognition approach with a cross-linguistic framework to arrive at a third position: that humans begin with the same spatial reference frames as our near relatives, the great apes, and diverge later owing to the influence of language and culture.

  12. Aquatic ape theory and fossil hominids.

    PubMed

    Verhaegen, M J

    1991-06-01

    While most older palaeo-anthropological studies emphasise the similarities of the fossil hominids with modern man, recent studies often stress the unique and the apelike features of the australopithecine dentitions, skulls and postcranial bones. It is worth reconsidering the features of Australopithecus, Homo erectus and Homo neanderthalensis in the light of the so-called Aquatic Ape Theory (AAT) of Hardy and Morgan, and to compare the skeletal parts of our fossil relatives with those of (semi)aquatic animals. Possible convergences are observed with proboscis monkeys, beavers, sea-otters, hippopotamuses, seals, sea-lions, walruses, sea-cows, whales, dolphins, porpoises, penguins and crocodiles.

  13. Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.

    PubMed

    Choi, Sunga; Shin, Ju Hyun; Lee, Yu Ran; Joo, Hee Kyoung; Song, Ki Hak; Na, Yong Gil; Chang, Seok Jong; Lim, Jae Sung; Jeon, Byeong Hwa

    2016-01-01

    Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.

  14. A Competitive Nonverbal False Belief Task for Children and Apes

    ERIC Educational Resources Information Center

    Krachun, Carla; Carpenter, Malinda; Call, Josep; Tomasello, Michael

    2009-01-01

    A nonverbal false belief task was administered to children (mean age 5 years) and two great ape species: chimpanzees ("Pan troglodytes") and bonobos ("Pan paniscus"). Because apes typically perform poorly in cooperative contexts, our task was competitive. Two versions were run: in both, a human competitor witnessed an experimenter hide a reward in…

  15. A Competitive Nonverbal False Belief Task for Children and Apes

    ERIC Educational Resources Information Center

    Krachun, Carla; Carpenter, Malinda; Call, Josep; Tomasello, Michael

    2009-01-01

    A nonverbal false belief task was administered to children (mean age 5 years) and two great ape species: chimpanzees ("Pan troglodytes") and bonobos ("Pan paniscus"). Because apes typically perform poorly in cooperative contexts, our task was competitive. Two versions were run: in both, a human competitor witnessed an experimenter hide a reward in…

  16. Do Great Apes Use Emotional Expressions to Infer Desires?

    ERIC Educational Resources Information Center

    Buttelmann, David; Call, Josep; Tomasello, Michael

    2009-01-01

    Although apes understand others' goals and perceptions, little is known about their understanding of others' emotional expressions. We conducted three studies following the general paradigm of Repacholi and colleagues (1997, 1998). In Study 1, a human reacted emotionally to the hidden contents of two boxes, after which the ape was allowed to…

  17. Do Great Apes Use Emotional Expressions to Infer Desires?

    ERIC Educational Resources Information Center

    Buttelmann, David; Call, Josep; Tomasello, Michael

    2009-01-01

    Although apes understand others' goals and perceptions, little is known about their understanding of others' emotional expressions. We conducted three studies following the general paradigm of Repacholi and colleagues (1997, 1998). In Study 1, a human reacted emotionally to the hidden contents of two boxes, after which the ape was allowed to…

  18. Ape language research: A review and behavioral perspective

    PubMed Central

    Hixson, Michael D.

    1998-01-01

    The ape language research of the Gardners, Fouts, Terrace, Rumbaugh, and Savage-Rumbaugh is reviewed. This research involved the raising of chimpanzees (and a bonobo) in human-like environments over extended time periods. The results indicate that apes are capable of learning small verbal repertoires in a fashion similar to that of human infants. The writings of the ape language researchers show an opposition to behavioral approaches to language. Although they characterize each other's work as behavioral, they oppose such explanations applied to their own work. A behavior-analytic approach to language has much empirical support, and behavioral treatments for people with language delays have produced substantial results. Despite the protestations of the ape language researchers, now is an appropriate time to apply the extensive knowledge base derived from a science of behavior to language acquisition in apes. PMID:22477125

  19. Apes have culture but may not know that they do.

    PubMed

    Gruber, Thibaud; Zuberbühler, Klaus; Clément, Fabrice; van Schaik, Carel

    2015-01-01

    There is good evidence that some ape behaviors can be transmitted socially and that this can lead to group-specific traditions. However, many consider animal traditions, including those in great apes, to be fundamentally different from human cultures, largely because of lack of evidence for cumulative processes and normative conformity, but perhaps also because current research on ape culture is usually restricted to behavioral comparisons. Here, we propose to analyze ape culture not only at the surface behavioral level but also at the underlying cognitive level. To this end, we integrate empirical findings in apes with theoretical frameworks developed in developmental psychology regarding the representation of tools and the development of metarepresentational abilities, to characterize the differences between ape and human cultures at the cognitive level. Current data are consistent with the notion of apes possessing mental representations of tools that can be accessed through re-representations: apes may reorganize their knowledge of tools in the form of categories or functional schemes. However, we find no evidence for metarepresentations of cultural knowledge: apes may not understand that they or others hold beliefs about their cultures. The resulting Jourdain Hypothesis, based on Molière's character, argues that apes express their cultures without knowing that they are cultural beings because of cognitive limitations in their ability to represent knowledge, a determining feature of modern human cultures, allowing representing and modifying the current norms of the group. Differences in metarepresentational processes may thus explain fundamental differences between human and other animals' cultures, notably limitations in cumulative behavior and normative conformity. Future empirical work should focus on how animals mentally represent their cultural knowledge to conclusively determine the ways by which humans are unique in their cultural behavior.

  20. Apes have culture but may not know that they do

    PubMed Central

    Gruber, Thibaud; Zuberbühler, Klaus; Clément, Fabrice; van Schaik, Carel

    2015-01-01

    There is good evidence that some ape behaviors can be transmitted socially and that this can lead to group-specific traditions. However, many consider animal traditions, including those in great apes, to be fundamentally different from human cultures, largely because of lack of evidence for cumulative processes and normative conformity, but perhaps also because current research on ape culture is usually restricted to behavioral comparisons. Here, we propose to analyze ape culture not only at the surface behavioral level but also at the underlying cognitive level. To this end, we integrate empirical findings in apes with theoretical frameworks developed in developmental psychology regarding the representation of tools and the development of metarepresentational abilities, to characterize the differences between ape and human cultures at the cognitive level. Current data are consistent with the notion of apes possessing mental representations of tools that can be accessed through re-representations: apes may reorganize their knowledge of tools in the form of categories or functional schemes. However, we find no evidence for metarepresentations of cultural knowledge: apes may not understand that they or others hold beliefs about their cultures. The resulting Jourdain Hypothesis, based on Molière’s character, argues that apes express their cultures without knowing that they are cultural beings because of cognitive limitations in their ability to represent knowledge, a determining feature of modern human cultures, allowing representing and modifying the current norms of the group. Differences in metarepresentational processes may thus explain fundamental differences between human and other animals’ cultures, notably limitations in cumulative behavior and normative conformity. Future empirical work should focus on how animals mentally represent their cultural knowledge to conclusively determine the ways by which humans are unique in their cultural behavior. PMID

  1. Were Australopithecines Ape-Human Intermediates or Just Apes? A Test of Both Hypotheses Using the "Lucy" Skeleton

    ERIC Educational Resources Information Center

    Senter, Phil

    2010-01-01

    Mainstream scientists often claim that australopithecines such as the specimen nicknamed "Lucy" exhibit anatomy intermediate between that of apes and that of humans and use this as evidence that humans evolved from australopithecines, which evolved from apes. On the other hand, creationists reject evolution and claim that australopithecines are…

  2. Were Australopithecines Ape-Human Intermediates or Just Apes? A Test of Both Hypotheses Using the "Lucy" Skeleton

    ERIC Educational Resources Information Center

    Senter, Phil

    2010-01-01

    Mainstream scientists often claim that australopithecines such as the specimen nicknamed "Lucy" exhibit anatomy intermediate between that of apes and that of humans and use this as evidence that humans evolved from australopithecines, which evolved from apes. On the other hand, creationists reject evolution and claim that australopithecines are…

  3. Are there geniuses among the apes?

    PubMed

    Herrmann, Esther; Call, Josep

    2012-10-05

    We are often asked whether some apes are smarter than others. Here we used two individual-based datasets on cognitive abilities to answer this question and to elucidate the structure of individual differences. We identified some individuals who consistently scored well across multiple tasks, and even one individual who could be classified as exceptional when compared with her conspecifics. However, we found no general intelligence factor. Instead, we detected some clusters of certain abilities, including inferences, learning and perhaps a tool-use and quantities cluster. Thus, apes in general and chimpanzees in particular present a pattern characterized by the existence of some smart animals but no evidence of a general intelligence factor. This conclusion contrasts with previous studies that have found evidence of a g factor in primates. However, those studies have used group-based as opposed to the individual-based data used here, which means that the two sets of analyses are not directly comparable. We advocate an approach based on testing multiple individuals (of multiple species) on multiple tasks that capture cognitive, motivational and temperament factors affecting performance. One of the advantages of this approach is that it may contribute to reconcile the general and domain-specific views on primate intelligence.

  4. Are there geniuses among the apes?

    PubMed Central

    Herrmann, Esther; Call, Josep

    2012-01-01

    We are often asked whether some apes are smarter than others. Here we used two individual-based datasets on cognitive abilities to answer this question and to elucidate the structure of individual differences. We identified some individuals who consistently scored well across multiple tasks, and even one individual who could be classified as exceptional when compared with her conspecifics. However, we found no general intelligence factor. Instead, we detected some clusters of certain abilities, including inferences, learning and perhaps a tool-use and quantities cluster. Thus, apes in general and chimpanzees in particular present a pattern characterized by the existence of some smart animals but no evidence of a general intelligence factor. This conclusion contrasts with previous studies that have found evidence of a g factor in primates. However, those studies have used group-based as opposed to the individual-based data used here, which means that the two sets of analyses are not directly comparable. We advocate an approach based on testing multiple individuals (of multiple species) on multiple tasks that capture cognitive, motivational and temperament factors affecting performance. One of the advantages of this approach is that it may contribute to reconcile the general and domain-specific views on primate intelligence. PMID:22927574

  5. The nerve supply to coracobrachialis in apes.

    PubMed Central

    Koizumi, M; Sakai, T

    1995-01-01

    The origin of the nerve supply to coracobrachialis from the brachial plexus in apes was investigated in 4 arms from 4 chimpanzees, both arms of a gorilla and 4 arms from 4 gibbons. The general architecture of the brachial plexus was the same as in the human. In the apes examined, the nerves supplying this muscle could be classified into 2 groups: (1) distal branches arising from the musculocutaneous nerve, and (2) proximal branches arising in the region of the lateral cord. On the basis of their origin and course, the proximal branches were classified into 3 types, namely a deep ramus arising from the middle trunk and passing dorsal to the upper trunk, a medial ramus arising from the upper trunk in the lateral cord, and a superficial ramus arising from the ventral surface of the middle trunk or the root of the pectoral nerve. This classification also applies to branches to coracobrachialis in man. The 3 types of proximal branch often communicated with each other to supply coracobrachialis, whereas the proximal and distal branches were separated from each other spatially. This indicates that coracobrachialis possesses characteristics both of the pectoral girdle muscles and the flexor muscles of the upper arm. Images Fig. 3 PMID:7649839

  6. Capturing snapshots of APE1 processing DNA damage

    SciTech Connect

    Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; Dyrkheeva, Nadezhda S.; Wilson, Samuel H.

    2015-10-12

    DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylated CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.

  7. Capturing Snapshots of APE1 Processing DNA Damage

    PubMed Central

    Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; Dyrkheeva, Nadezhda S.; Wilson, Samuel H.

    2015-01-01

    DNA apurinic-apyrimidinic (AP) sites are prevalent non-coding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive due in part to limited structural information. We report multiple high-resolution human APE1:DNA structures that divulge novel features of the APE1 reaction, including the metal binding site, nucleophile, and arginine clamps that mediate product release. We also report APE1:DNA structures with a T:G mismatch 5′ to the AP-site, representing a clustered lesion occurring in methylated CpG dinucleotides. These reveal that APE1 molds the T:G mismatch into a unique Watson-Crick like geometry that distorts the active site reducing incision. These snapshots provide mechanistic clarity for APE1, while affording a rational framework to manipulate biological responses to DNA damage. PMID:26458045

  8. Capturing snapshots of APE1 processing DNA damage

    DOE PAGES

    Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; ...

    2015-10-12

    DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylatedmore » CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.« less

  9. Paleoenvironmental basis of cognitive evolution in great apes.

    PubMed

    Potts, Richard

    2004-03-01

    A bias favoring tree-dominated habitats and ripe-fruit frugivory has persisted in great ape evolution since the early Miocene. This bias is indicated by fossil ape paleoenvironments, molar morphology, dental microwear, the geographic pattern of extinctions, and extant apes' reliance on wooded settings. The ephemeral aspect of high-quality fruit has placed a premium on cognitive and social means of finding and defending food sources, and appears related to great apes' affinity since the Miocene for wooded, fruit-rich environments. These habitats have, however, undergone a severe withdrawal toward the low latitudes of Africa and Southeast Asia since the late Miocene, corresponding to a decline in the diversity of great apes beginning 9.5 million years ago. Plio-Pleistocene records imply that wooded settings of Africa and SE Asia were prone to substantial fragmentation and coalescence. Once apes were confined to equatorial settings, therefore, habitat instability heightened the spatial/temporal uncertainty of ripe-fruit sources. Prolonged learning, the assignment of attributes to distant places, mental representation, and reliance on fallback foods were all favored in this dynamic environmental context. These abilities helped sustain forest frugivory in most lineages. Fluid social grouping afforded the animals opportunities to locate ephemeral foods in continuous and fragmented forests. Fission-fusion grouping also magnified the problems of object impermanence (of individuals) and dispersion manifested by food sources in the ecological realm. Thus the spatial and temporal dynamics of fruit and wooded habitats since the Miocene are reflected in important components of great ape cognition, foraging, and sociality. In contrast to great apes, cercopithecoid monkeys have increased their plant dietary options and diversified in seasonal environments since the late Miocene. Early hominins eventually severed the habitat bias that characterized the evolution of great apes, and

  10. Lower Ilium Evolution in Apes and Hominins.

    PubMed

    Hammond, Ashley S; Almécija, Sergio

    2017-05-01

    Elucidating the pelvic morphology of the Pan-Homo last common ancestor (LCA) is crucial for understanding ape and human evolution. The pelvis of Ardipithecus ramidus has been the basis of controversial interpretations of the LCA pelvis. In particular, it was proposed that the lower ilium became elongate independently in the orangutan and chimpanzee clades, making these taxa poor analogues for the pelvis of the LCA. This study examines the variation in relative lower ilium height between and within living and fossil hominoid species (and other anthropoids), and models its evolution using available fossil hominoids as calibration points. We find nuanced differences in relative lower ilium height among living hominoids, particularly in regards to gorillas, which do not have elongate lower ilia (because they are likely to represent the plesiomorphic hominoid condition for this trait). We also show that differences in relative lower ilium height among hominoid taxa are not readily explained by differences in size between species. Our maximum likelihood ancestral state reconstructions support inferences that chimpanzees (Pan troglodytes in particular) and orangutans evolved their elongate lower ilia independently. We also find that the predicted lower ilium height of the Pan-Homo LCA is shorter than all great apes except gorillas. This study adds to a growing body of evidence that finds different regions of the body show different evolutionary histories in different hominoids, and underscores that the unique combinations of morphologies of each modern and fossil hominoid species should be considered when reconstructing the mosaic nature of the Pan-Homo LCA. Anat Rec, 300:828-844, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. The biology of the colonizing ape.

    PubMed

    Wells, Jonathan C K; Stock, Jay T

    2007-01-01

    Hominin evolutionary history is characterized by regular dispersals, cycles of colonization, and entry into novel environments. This article considers the relationship between such colonizing capacity and hominin biology. In general, colonizing strategy favors rapid rates of reproduction and generalized rather than specialized biology. Physiological viability across diverse environments favors a high degree of phenotypic plasticity, which buffers the genome from selective pressures. Colonizing also favors the capacity to access and process information about environmental variability. We propose that early hominin adaptive radiations were based upon the development of such capacities as adaptations to unstable Pliocene environments. These components came together, along with fundamental changes in morphology, behavior, and cognition in the genus Homo, who exploited them in subsequent wider dispersals. Middle Pleistocene hominins and modern humans also show development of further traits, which correspond with successful probing of, and dispersals into, stressful environments. These traits have their precursors in primate or ape biology, but have become more pronounced during hominin evolution. First, short interbirth intervals and slow childhood growth allow human females to provision several offspring simultaneously, increasing the rate of reproduction in favorable conditions. This allows rapid recovery from population crashes, or rapid population growth in new habitats. Second, despite high geographical phenotypic variability, humans have high genetic unity. This is achieved by a variety of levels of plasticity, including physiology, behavior, and technology, which reduce the need to commit to genetic adaptation. Hominin behavior may increasingly have shaped both the ecological niches occupied and the selective pressures acting back on the genome. Such selective pressures may have been exacerbated by population dynamics, predicted to both derive from, and favor

  12. Comparative Pathology of Aging Great Apes: Bonobos, Chimpanzees, Gorillas, and Orangutans.

    PubMed

    Lowenstine, L J; McManamon, R; Terio, K A

    2016-03-01

    The great apes (chimpanzees, bonobos, gorillas, and orangutans) are our closest relatives. Despite the many similarities, there are significant differences in aging among apes, including the human ape. Common to all are dental attrition, periodontitis, tooth loss, osteopenia, and arthritis, although gout is uniquely human and spondyloarthropathy is more prevalent in apes than humans. Humans are more prone to frailty, sarcopenia, osteoporosis, longevity past reproductive senescence, loss of brain volume, and Alzheimer dementia. Cerebral vascular disease occurs in both humans and apes. Cardiovascular disease mortality increases in aging humans and apes, but coronary atherosclerosis is the most significant type in humans. In captive apes, idiopathic myocardial fibrosis and cardiomyopathy predominate, with arteriosclerosis of intramural coronary arteries. Similar cardiac lesions are occasionally seen in wild apes. Vascular changes in heart and kidneys and aortic dissections in gorillas and bonobos suggest that hypertension may be involved in pathogenesis. Chronic kidney disease is common in elderly humans and some aging apes and is linked with cardiovascular disease in orangutans. Neoplasms common to aging humans and apes include uterine leiomyomas in chimpanzees, but other tumors of elderly humans, such as breast, prostate, lung, and colorectal cancers, are uncommon in apes. Among the apes, chimpanzees have been best studied in laboratory settings, and more comparative research is needed into the pathology of geriatric zoo-housed and wild apes. Increasing longevity of humans and apes makes understanding aging processes and diseases imperative for optimizing quality of life in all the ape species. © The Author(s) 2015.

  13. A competitive nonverbal false belief task for children and apes.

    PubMed

    Krachun, Carla; Carpenter, Malinda; Call, Josep; Tomasello, Michael

    2009-07-01

    A nonverbal false belief task was administered to children (mean age 5 years) and two great ape species: chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). Because apes typically perform poorly in cooperative contexts, our task was competitive. Two versions were run: in both, a human competitor witnessed an experimenter hide a reward in one of two containers. When the competitor then left the room (version A) or turned around (version B), the experimenter switched the locations of the containers. The competitor returned and reached with effort, but unsuccessfully, towards the incorrect container. Children displayed an understanding of the competitor's false belief by correctly choosing the other container to find the reward. Apes did not. However, in version A (but not version B), apes looked more often at the unchosen container in false belief trials than in true belief control trials, possibly indicating some implicit or uncertain understanding that needs to be investigated further.

  14. The evolution of human and ape hand proportions.

    PubMed

    Almécija, Sergio; Smaers, Jeroen B; Jungers, William L

    2015-07-14

    Human hands are distinguished from apes by possessing longer thumbs relative to fingers. However, this simple ape-human dichotomy fails to provide an adequate framework for testing competing hypotheses of human evolution and for reconstructing the morphology of the last common ancestor (LCA) of humans and chimpanzees. We inspect human and ape hand-length proportions using phylogenetically informed morphometric analyses and test alternative models of evolution along the anthropoid tree of life, including fossils like the plesiomorphic ape Proconsul heseloni and the hominins Ardipithecus ramidus and Australopithecus sediba. Our results reveal high levels of hand disparity among modern hominoids, which are explained by different evolutionary processes: autapomorphic evolution in hylobatids (extreme digital and thumb elongation), convergent adaptation between chimpanzees and orangutans (digital elongation) and comparatively little change in gorillas and hominins. The human (and australopith) high thumb-to-digits ratio required little change since the LCA, and was acquired convergently with other highly dexterous anthropoids.

  15. The evolution of human and ape hand proportions

    PubMed Central

    Almécija, Sergio; Smaers, Jeroen B.; Jungers, William L.

    2015-01-01

    Human hands are distinguished from apes by possessing longer thumbs relative to fingers. However, this simple ape-human dichotomy fails to provide an adequate framework for testing competing hypotheses of human evolution and for reconstructing the morphology of the last common ancestor (LCA) of humans and chimpanzees. We inspect human and ape hand-length proportions using phylogenetically informed morphometric analyses and test alternative models of evolution along the anthropoid tree of life, including fossils like the plesiomorphic ape Proconsul heseloni and the hominins Ardipithecus ramidus and Australopithecus sediba. Our results reveal high levels of hand disparity among modern hominoids, which are explained by different evolutionary processes: autapomorphic evolution in hylobatids (extreme digital and thumb elongation), convergent adaptation between chimpanzees and orangutans (digital elongation) and comparatively little change in gorillas and hominins. The human (and australopith) high thumb-to-digits ratio required little change since the LCA, and was acquired convergently with other highly dexterous anthropoids. PMID:26171589

  16. What's Special about Human Imitation? A Comparison with Enculturated Apes.

    PubMed

    Subiaul, Francys

    2016-07-07

    What, if anything, is special about human imitation? An evaluation of enculturated apes' imitation skills, a "best case scenario" of non-human apes' imitation performance, reveals important similarities and differences between this special population of apes and human children. Candidates for shared imitation mechanisms include the ability to imitate various familiar transitive responses and object-object actions that involve familiar tools. Candidates for uniquely derived imitation mechanisms include: imitating novel transitive actions and novel tool-using responses as well as imitating opaque or intransitive gestures, regardless of familiarity. While the evidence demonstrates that enculturated apes outperform non-enculturated apes and perform more like human children, all apes, regardless of rearing history, generally excel at imitating familiar, over-rehearsed responses and are poor, relative to human children, at imitating novel, opaque or intransitive responses. Given the similarities between the sensory and motor systems of preschool age human children and non-human apes, it is unlikely that differences in sensory input and/or motor-output alone explain the observed discontinuities in imitation performance. The special rearing history of enculturated apes-including imitation-specific training-further diminishes arguments suggesting that differences are experience-dependent. Here, it is argued that such differences are best explained by distinct, specialized mechanisms that have evolved for copying rules and responses in particular content domains. Uniquely derived social and imitation learning mechanisms may represent adaptations for learning novel communicative gestures and complex tool-use. Given our species' dependence on both language and tools, mechanisms that accelerated learning in these domains are likely to have faced intense selective pressures, starting with the earliest of human ancestors.

  17. Miocene hominoid craniofacial morphology and the emergence of great apes.

    PubMed

    Rae, Todd C

    2004-12-01

    The initial cladogenic event between Hominoidea (apes, including humans) and Cercopithecoidea (Old World monkeys) consisted primarily of changes in the craniofacial region. These changes, seen in taxa commonly known as victoriapithecids and proconsulids, arose in a mosaic fashion. The divergence in the postcranium was more subtle; there are strong suggestions that apes initially adopted a tail-less pronograde arboreal quadrupedalism, while cercopithecoids became better adapted to a more terrestrial lifestyle. Recent phylogenetic analysis suggests that gibbons (Hylobates) have reversed derived craniofacial characters autapomorphically, contradicting the interpretation that the origin of apes sensu stricto coincides with the emergence of suspensory adaptations. The suspensory postcranium evolved later and appeared first in Eurasia; recent palaeobiogeographic reconstructions suggest that suspensory apes subsequently re-colonized Africa, as suggested nearly thirty years ago on neontological grounds. To test whether these two models of hominoid evolution are compatible, catarrhine craniofacial and postcranial traits, including those from Eurasian fossils, were subjected to parsimony analysis. The results demonstrate a mosaic pattern of derived characters, with gibbons reversing some traits of the face, which suggests their derivation from a 'great ape' face. Combined with the palaeobiogeography, a much longer, step-wise transition from primitive catarrhines to extant great apes than previously envisioned is supported. The pattern of craniofacial change is difficult to interpret in functional/adaptational terms, but the origin of brachiation may have arisen through character displacement due to competition with the emerging modern Old World monkey radiation in Eurasia.

  18. Language comprehension in ape and child.

    PubMed

    Savage-Rumbaugh, E S; Murphy, J; Sevcik, R A; Brakke, K E; Williams, S L; Rumbaugh, D M

    1993-01-01

    Previous investigations of the linguistic capacities of apes have focused on the ape's ability to produce words, and there has been little concern for comprehension. By contrast, it is increasingly recognized that comprehension precedes production in the language development of normal human children, and it may indeed guide production. It has been demonstrated that some species can process speech sounds categorically in a manner similar to that observed in humans. Consequently, it should be possible for such species to comprehend language if they have the cognitive capacity to understand word-referent relations and syntactic structure. Popular theories of human language acquisition suggest that the ability to process syntactic information is unique to humans and reflects a novel biological adaptation not seen in other animals. The current report addresses this issue through systematic experimental comparisons of the language comprehension skills of a 2-year-old child and an 8 year-old bonobo (Pan paniscus) who was raised in a language environment similar to that in which children are raised but specifically modified to be appropriate for an ape. Both subjects (child and bonobo) were exposed to spoken English and lexigrams from infancy, and neither was trained to comprehend speech. A common caretaker participated in the rearing of both subjects. All language acquisition was through observational learning. Without prior training, subjects were asked to respond to the same 660 novel sentences. All responses were videotaped and scored for accuracy of comprehension of the English language. The results indicated that both subjects comprehended novel requests and simple syntactic devices. The bonobo decoded the syntactic device of word recursion with higher accuracy than the child; however, the child tended to do better than the bonobo on the conjunctive, a structure that places a greater burden on short-term memory. Both subjects performed as well on sentences that

  19. Sequential information in a great ape utterance

    PubMed Central

    Fedurek, Pawel; Zuberbühler, Klaus; Dahl, Christoph D.

    2016-01-01

    Birdsong is a prime example of acoustically sophisticated vocal behaviour, but its complexity has evolved mainly through sexual selection to attract mates and repel sexual rivals. In contrast, non-human primate calls often mediate complex social interactions, but are generally regarded as acoustically simple. Here, we examine arguably the most complex call in great ape vocal communication, the chimpanzee (Pan troglodytes schweinfurthii) ‘pant hoot’. This signal consists of four acoustically distinct phases: introduction, build-up, climax and let-down. We applied state-of-the-art Support Vector Machines (SVM) methodology to pant hoots produced by wild male chimpanzees of Budongo Forest, Uganda. We found that caller identity was apparent in all four phases, but most strongly in the low-amplitude introduction and high-amplitude climax phases. Age was mainly correlated with the low-amplitude introduction and build-up phases, dominance rank (i.e. social status) with the high-amplitude climax phase, and context (reflecting activity of the caller) with the low-amplitude let-down phase. We conclude that the complex acoustic structure of chimpanzee pant hoots is linked to a range of socially relevant information in the different phases of the call, reflecting the complex nature of chimpanzee social lives. PMID:27910886

  20. Natural Selection in the Great Apes

    PubMed Central

    Cagan, Alexander; Theunert, Christoph; Laayouni, Hafid; Santpere, Gabriel; Pybus, Marc; Casals, Ferran; Prüfer, Kay; Navarro, Arcadi; Marques-Bonet, Tomas; Bertranpetit, Jaume; Andrés, Aida M.

    2016-01-01

    Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh. PMID:27795229

  1. Natural Selection in the Great Apes.

    PubMed

    Cagan, Alexander; Theunert, Christoph; Laayouni, Hafid; Santpere, Gabriel; Pybus, Marc; Casals, Ferran; Prüfer, Kay; Navarro, Arcadi; Marques-Bonet, Tomas; Bertranpetit, Jaume; Andrés, Aida M

    2016-12-01

    Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Great ape foresight is looking great.

    PubMed

    Osvath, Mathias

    2010-09-01

    Suddendorf, Corballis and Collier-Baker (Anim Cogn 12: 751-754, 2009) comment on a study on great ape foresight (Osvath and Osvath, Anim Cogn 11: 661-674, 2008). That study consisted of four experiments investigating foresight in chimpanzees and orangutans, examining in particular whether the planning they exhibit is best explained by assuming an episodic cognitive system. This system has widely been regarded as exclusive to humans. Indeed, the Bischof-Köhler hypothesis explicitly states that planning for a future need is outside the abilities of non-humans. In our paper, we argued that the results implied the presence of episodic abilities and challenged the Bischof-Köhler hypothesis. Suddendorf et al. are not ready to accept this claim. They critique each experiment in detail and maintain their view that episodic cognition is unique to humans. Here, I point out the misapprehensions and weaknesses in their critique notably a lack of appreciation for how the experiments in the study are interrelated and serve as controls for each other and for the baseline experiment. I reinforce my earlier conclusions with a number of recently published findings.

  3. Inferential reasoning by exclusion in great apes, lesser apes, and spider monkeys.

    PubMed

    Hill, Andrew; Collier-Baker, Emma; Suddendorf, Thomas

    2011-02-01

    Using the cups task, in which subjects are presented with limited visual or auditory information that can be used to deduce the location of a hidden reward, Call (2004) found prima facie evidence of inferential reasoning by exclusion in several great ape species. One bonobo (Pan paniscus) and two gorillas (Gorilla gorilla) appeared to make such inferences in both the visual and auditory domains. However, common chimpanzees (Pan troglodytes) were successful only in the visual domain, and Bornean orangutans (Pongo pygmaeus) in neither. The present research built on this paradigm, and Experiment 1 yielded prima facie evidence of inference by exclusion in both domains for two common chimpanzees, and in the visual domain for two Sumatran orangutans (Pongo abelii). Experiments 2 and 3 demonstrated that two specific associative learning explanations could not readily account for these results. Because an important focus of the program of research was to assess the cognitive capacities of lesser apes (family Hylobatidae), we modified Call's original procedures to better suit their attentional and dispositional characteristics. In Experiment 1, testing was also attempted with three gibbon genera (Symphalangus, Nomascus, Hylobates), but none of the subjects completed the standard task. Further testing of three siamangs (Symphalangus syndactylus) and a spider monkey (Ateles geoffroyi) using a faster method yielded prima facie evidence of inferential reasoning by exclusion in the visual domain among the siamangs (Experiment 4).

  4. Development of APE1 enzymatic DNA repair assays: low APE1 activity is associated with increase lung cancer risk.

    PubMed

    Sevilya, Ziv; Leitner-Dagan, Yael; Pinchev, Mila; Kremer, Ran; Elinger, Dalia; Lejbkowicz, Flavio; Rennert, Hedy S; Freedman, Laurence S; Rennert, Gad; Paz-Elizur, Tamar; Livneh, Zvi

    2015-09-01

    The key role of DNA repair in removing DNA damage and minimizing mutations makes it an attractive target for cancer risk assessment and prevention. Here we describe the development of a robust assay for apurinic/apyrimidinic (AP) endonuclease 1 (APE1; APEX1), an essential enzyme involved in the repair of oxidative DNA damage. APE1 DNA repair enzymatic activity was measured in peripheral blood mononuclear cell protein extracts using a radioactivity-based assay, and its association with lung cancer was determined using conditional logistic regression with specimens from a population-based case-control study with 96 lung cancer cases and 96 matched control subjects. The mean APE1 enzyme activity in case patients was 691 [95% confidence interval (CI) = 655-727] units/ng protein, significantly lower than in control subjects (mean = 793, 95% CI = 751-834 units/ng protein, P = 0.0006). The adjusted odds ratio for lung cancer associated with 1 SD (211 units) decrease in APE1 activity was 2.0 (95% CI = 1.3-3.1; P = 0.002). Comparison of radioactivity- and fluorescence-based assays showed that the two are equivalent, indicating no interference by the fluorescent tag. The APE1Asp148Glu SNP was associated neither with APE1 enzyme activity nor with lung cancer risk. Taken together, our results indicate that low APE1 activity is associated with lung cancer risk, consistent with the hypothesis that 'bad DNA repair', rather than 'bad luck', is involved in cancer etiology. Such assays may be useful, along with additional DNA repair biomarkers, for risk assessment of lung cancer and perhaps other cancers, and for selecting individuals to undergo early detection techniques such as low-dose CT.

  5. Does sympathy motivate prosocial behaviour in great apes?

    PubMed

    Liebal, Katja; Vaish, Amrisha; Haun, Daniel; Tomasello, Michael

    2014-01-01

    Prosocial behaviours such as helping, comforting, or sharing are central to human social life. Because they emerge early in ontogeny, it has been proposed that humans are prosocial by nature and that from early on empathy and sympathy motivate such behaviours. The emerging question is whether humans share these abilities to feel with and for someone with our closest relatives, the great apes. Although several studies demonstrated that great apes help others, little is known about their underlying motivations. This study addresses this issue and investigates whether four species of great apes (Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, Pan paniscus) help a conspecific more after observing the conspecific being harmed (a human experimenter steals the conspecific's food) compared to a condition where no harming occurred. Results showed that in regard to the occurrence of prosocial behaviours, only orangutans, but not the African great apes, help others when help is needed, contrasting prior findings on chimpanzees. However, with the exception of one population of orangutans that helped significantly more after a conspecific was harmed than when no harm occurred, prosocial behaviour in great apes was not motivated by concern for others.

  6. Looking in apes as a source of human pathogens.

    PubMed

    Keita, Mamadou B; Hamad, Ibrahim; Bittar, Fadi

    2014-12-01

    Because of the close genetic relatedness between apes and humans, apes are susceptible to many human infectious agents and can serve as carriers of these pathogens. Consequently, they present a serious health hazard to humans. Moreover, many emerging infectious diseases originate in wildlife and continue to threaten human populations, especially vector-borne diseases described in great apes, such as malaria and rickettsiosis. These wild primates may be permanent reservoirs and important sources of human pathogens. In this special issue, we report that apes, including chimpanzees (Pan troglodytes), bonobos (Pan paniscus), gorillas (Gorilla gorilla and Gorilla beringei), orangutans (Pongo pygmaeus and Pongo abelii), gibbons (Hylobates spp., Hoolock spp. and Nomascus spp) and siamangs (Symphalangus syndactylus syndactylus and Symphalangus continentis), have many bacterial, viral, fungal and parasitic species that are capable of infecting humans. Serious measures should be adopted in tropical forests and sub-tropical areas where habitat overlaps are frequent to survey and prevent infectious diseases from spreading from apes to people. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Does Sympathy Motivate Prosocial Behaviour in Great Apes?

    PubMed Central

    Liebal, Katja; Vaish, Amrisha; Haun, Daniel; Tomasello, Michael

    2014-01-01

    Prosocial behaviours such as helping, comforting, or sharing are central to human social life. Because they emerge early in ontogeny, it has been proposed that humans are prosocial by nature and that from early on empathy and sympathy motivate such behaviours. The emerging question is whether humans share these abilities to feel with and for someone with our closest relatives, the great apes. Although several studies demonstrated that great apes help others, little is known about their underlying motivations. This study addresses this issue and investigates whether four species of great apes (Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, Pan paniscus) help a conspecific more after observing the conspecific being harmed (a human experimenter steals the conspecific’s food) compared to a condition where no harming occurred. Results showed that in regard to the occurrence of prosocial behaviours, only orangutans, but not the African great apes, help others when help is needed, contrasting prior findings on chimpanzees. However, with the exception of one population of orangutans that helped significantly more after a conspecific was harmed than when no harm occurred, prosocial behaviour in great apes was not motivated by concern for others. PMID:24416212

  8. Will oil palm's homecoming spell doom for Africa's great apes?

    PubMed

    Wich, Serge A; Garcia-Ulloa, John; Kühl, Hjalmar S; Humle, Tatanya; Lee, Janice S H; Koh, Lian Pin

    2014-07-21

    Expansion of oil palm plantations has led to extensive wildlife habitat conversion in Southeast Asia [1]. This expansion is driven by a global demand for palm oil for products ranging from foods to detergents [2], and more recently for biofuels [3]. The negative impacts of oil palm development on biodiversity [1, 4, 5], and on orangutans (Pongo spp.) in particular, have been well documented [6, 7] and publicized [8, 9]. Although the oil palm is of African origin, Africa's production historically lags behind that of Southeast Asia. Recently, significant investments have been made that will likely drive the expansion of Africa's oil palm industry [10]. There is concern that this will lead to biodiversity losses similar to those in Southeast Asia. Here, we analyze the potential impact of oil palm development on Africa's great apes. Current great ape distribution in Africa substantially overlaps with current oil palm concessions (by 58.7%) and areas suitable for oil palm production (by 42.3%). More importantly, 39.9% of the distribution of great ape species on unprotected lands overlaps with suitable oil palm areas. There is an urgent need to develop guidelines for the expansion of oil palm in Africa to minimize the negative effects on apes and other wildlife. There is also a need for research to support land use decisions to reconcile economic development, great ape conservation, and avoiding carbon emissions.

  9. Ape metaphysics: object individuation without language.

    PubMed

    Mendes, Natacha; Rakoczy, Hannes; Call, Josep

    2008-02-01

    Developmental research suggests that whereas very young infants individuate objects purely on spatiotemporal grounds, from (at latest) around 1 year of age children are capable of individuating objects according to the kind they belong to and the properties they instantiate. As the latter ability has been found to correlate with language, some have speculated whether it might be essentially language dependent and therefore uniquely human. Existing studies with non-human primates seem to speak against this hypothesis, but fail to present conclusive evidence due to methodological shortcomings. In the present experiments we set out to test non-linguistic object individuation in three great ape species with a refined manual search methodology. Experiment 1 tested for spatiotemporal object individuation: Subjects saw 1 or 2 objects simultaneously being placed inside a box in which they could reach, and then in both conditions only found 1 object. After retrieval of the 1 object, subjects reached again significantly more often when they had seen 2 than when they had seen 1 object. Experiment 2 tested for object individuation according to property/kind information only: Subjects saw 1 object being placed inside the box, and then either found that object (expected) or an object of a different kind (unexpected). Analogously to Experiment 1, after retrieval of the 1 object, subjects reached again significantly more often in the unexpected than in the expected condition. These results thus confirm previous findings suggesting that individuating objects according to their property/kind is neither uniquely human nor essentially language dependent. It remains to be seen, however, whether this kind of object individuation requires sortal concepts as human linguistic thinkers use them, or whether some simpler form of tracking properties is sufficient.

  10. Comparative and Familial Analysis of Handedness in Great Apes

    PubMed Central

    Hopkins, William D.

    2007-01-01

    Historically, population-level handedness has been considered a hallmark of human evolution. Whether nonhuman primates exhibit population-level handedness remains a topic of considerable debate. This paper summarizes published data on handedness in great apes. Comparative analysis indicated that chimpanzees and bonobos show population-level right handedness, whereas gorillas and orangutans do not. All ape species showed evidence of population-level handedness when considering specific tasks. Familial analyses in chimpanzees indicated that offspring and maternal (but not paternal) handedness was significantly positively correlated, but this finding was contingent upon the classification criteria used to evaluate hand preference. Overall, the proportion of right handedness is lower in great apes compared with humans, and various methodological and theoretical explanations for this discrepancy are discussed. PMID:16822166

  11. A New Approach for Monitoring Ebolavirus in Wild Great Apes

    PubMed Central

    Cameron, Kenneth N.; Ondzie, Alain U.; Joly, Damien; Bermejo, Magdalena; Rouquet, Pierre; Fabozzi, Giulia; Bailey, Michael; Shen, Zhimin; Keele, Brandon F.; Hahn, Beatrice; Karesh, William B.; Sullivan, Nancy J.

    2014-01-01

    Background Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. Methodology/Principal findings Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). Conclusions/Significance Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%. PMID:25232832

  12. Differences in the Nonverbal Requests of Great Apes and Human Infants

    ERIC Educational Resources Information Center

    van der Goot, Marloes H.; Tomasello, Michael; Liszkowski, Ulf

    2014-01-01

    This study investigated how great apes and human infants use imperative pointing to request objects. In a series of three experiments (infants, N = 44; apes, N = 12), subjects were given the opportunity to either point to a desired object from a distance or else to approach closer and request it proximally. The apes always approached close to the…

  13. Differences in the Nonverbal Requests of Great Apes and Human Infants

    ERIC Educational Resources Information Center

    van der Goot, Marloes H.; Tomasello, Michael; Liszkowski, Ulf

    2014-01-01

    This study investigated how great apes and human infants use imperative pointing to request objects. In a series of three experiments (infants, N = 44; apes, N = 12), subjects were given the opportunity to either point to a desired object from a distance or else to approach closer and request it proximally. The apes always approached close to the…

  14. Meaning and ostension in great ape gestural communication.

    PubMed

    Moore, Richard

    2016-01-01

    It is sometimes argued that while human gestures are produced ostensively and intentionally, great ape gestures are produced only intentionally. If true, this would make the psychological mechanisms underlying the different species' communication fundamentally different, and ascriptions of meaning to chimpanzee gestures would be inappropriate. While the existence of different underlying mechanisms cannot be ruled out, in fact claims about difference are driven less by empirical data than by contested assumptions about the nature of ostensive communication. On some accounts, there are no reasons to doubt that great ape gestural communication is ostensive. If these accounts are correct, attributions of meaning to chimpanzee gestures would be justified.

  15. The Aquatic Ape Theory: evidence and a possible scenario.

    PubMed

    Verhaegen, M J

    1985-01-01

    Much more than other primates, man has several features that are seen more often in aquatic than terrestrial mammals: nakedness, thick subcutaneous fat-layer, stretched hindlimbs, voluntary respiration, dilute urine etc. The Aquatic Ape Theory states that our ancestors once spent a significant part of their life in water. Presumably, early apes were plant and fruit eaters in tropical forests. Early hominids also ate aquatic food; at first mainly weeds and tubers, later sea shore animals, especially shellfish. With the Pleistocene cooling, our ancestors returned to land and became bipedal omnivores and scavengers and later hunters of coastal and riverside animals.

  16. Human and ape: the legend, the history and the DNA

    PubMed Central

    Diamandopoulos, AA; Goudas, CP

    2007-01-01

    A vast amount of papers is published every year about species evolution, the most interesting being those recently published in the journal "Nature", concerning the human-ape relationship. The results and the new theories generated from this research are sometimes astonishing, rising not only biological, but also social, religious and cultural questions. One of the new questions concerns the role of species interbreeding as a means of evolution. In the subject of species interbreeding between human and ape we found some interesting historical and mythical information that sort of back-up this theory of interbreeding, with a historical and cultural side of view. PMID:19582186

  17. Great apes show highly selective plasma carotenoids and have physiologically high plasma retinyl esters compared to humans.

    PubMed

    García, Ada L; Raila, Jens; Koebnick, Corinna; Eulenberger, Klaus; Schweigert, Florian J

    2006-10-01

    Great apes are the closest living relatives of humans. Physiological similarities between great apes and humans provide clues to identify which biological features in humans are primitive or derived from great apes. Vitamin A (VA) and carotenoid metabolism have been only partially studied in great apes, and comparisons between great apes and humans are not available. We aimed to investigate VA and carotenoid intake and plasma concentrations in great apes living in captivity, and to compare them to healthy humans. Dietary intakes of humans (n = 20) and, among the great apes, chimpanzees (n = 15) and orangutans (n = 5) were calculated. Plasma retinol (ROH), retinol-binding protein (RBP), retinyl esters, and major carotenoids were analyzed. The great ape diet was higher in VA than in humans, due to high intake of provitamin A carotenoids. Plasma ROH concentrations in great apes were similar to those in humans, but retinyl esters were higher in great apes than in humans. Differences in plasma carotenoid concentrations were observed between great apes and humans. Lutein was the main carotenoid in great apes, while beta-carotene was the main carotenoid for humans. RBP concentrations did not differ between great apes and humans. The molar ratio of ROH to RBP was close to 1.0 in both great apes and humans. In conclusion, great apes show homeostatic ROH regulation, with high but physiological retinyl esters circulating in plasma. Furthermore, great apes show great selectivity in their plasmatic carotenoid concentration, which is not explained by dietary intake.

  18. Root growth during molar eruption in extant great apes.

    PubMed

    Kelley, Jay; Dean, Christopher; Ross, Sasha

    2009-01-01

    While there is gradually accumulating knowledge about molar crown formation and the timing of molar eruption in extant great apes, very little is known about root formation during the eruption process. We measured mandibular first and second molar root lengths in extant great ape osteological specimens that died while either the first or second molars were in the process of erupting. For most specimens, teeth were removed so that root lengths could be measured directly. When this was not possible, roots were measured radiographically. We were particularly interested in the variation in the lengths of first molar roots near the point of gingival emergence, so specimens were divided into early, middle and late phases of eruption based on the number of cusps that showed protein staining, with one or two cusps stained equated with immediate post-gingival emergence. For first molars at this stage, Gorilla has the longest roots, followed by Pongo and Pan. Variation in first molar mesial root lengths at this stage in Gorilla and Pan, which comprise the largest samples, is relatively low and represents no more than a few months of growth in both taxa. Knowledge of root length at first molar emergence permits an assessment of the contribution of root growth toward differences between great apes and humans in the age at first molar emergence. Root growth makes up a greater percentage of the time between birth and first molar emergence in humans than it does in any of the great apes.

  19. Ape limb bone from the oligocene of Egypt.

    PubMed

    Fleagle, J G; Simons, E L; Conroy, G C

    1975-07-11

    An ulna attributed to Aegyptopithecus zeuxis provides the first evidence for interpreting the locomotor behavior of the earliest apes. The fossil indicates that Aegyptopithecus was an arboreal quadruped and that the primitive hominoid locomotor pattern was most nearly analogous, among living primates, to that of Alouatta, the howler monkey.

  20. Phylogenetic Approach to Object Manipulation in Human and Ape Infants.

    ERIC Educational Resources Information Center

    Vauclair, Jacques

    1984-01-01

    Parker and Gibson's developmental model of evolution of language and intelligence in early hominids is described and discussed; data from a comparative study of object manipulation in two apes and a human infant are reported; and, human ontogenic developmental retardation in locomotion is discussed in terms of its implications for the differential…

  1. Extensive polymorphism in the mitochondrial DNA of apes.

    PubMed Central

    Ferris, S D; Brown, W M; Davidson, W S; Wilson, A C

    1981-01-01

    Ape species are 2-10 times more variable than the human species with respect to the nucleotide sequence of mtDNA, even though ape populations have been smaller than the human population for at least 10,000 years. This finding was made by comparing purified mtDNAs from 27 individuals with the aid of 25 restriction endonucleases; for an additional 59 individuals, comparisons were made with fewer enzymes by using the blot hybridization method. The amount of intraspecific sequence divergence was greatest between orangutans of Borneo and Sumatra. Among common chimpanzees, a large component of the variation is due to two highly distinct forms of mtDNA that may reflect a major geographic subdivision. The least amount of sequence variation occurred among lowland gorillas, which exhibit only twice as much sequence variation as humans. The large intraspecific differences among apes, together with the geological and protein evidence, leads us to propose that each ape species is the remnant of an ancient and widespread population that became subdivided geographically and reduced in size and range, perhaps by hominid competition. The low variation among human mtDNAs is consistent with geological evidence that the human species is young. The distribution of site changes within the mitochondrial genome was also examined. Comparison of closely related mtDNAs shows that the ribosomal RNA genes have diverged more slowly than the rest of the genome. PMID:6273863

  2. Comprehension of Novel Communicative Signs by Apes and Human Children.

    ERIC Educational Resources Information Center

    Tomasello, Michael; Call, Josep; Gluckman, Andrea

    1997-01-01

    Compared comprehension of novel communicative signs to assist 2.5- and 3-year-old humans, chimpanzees, and orangutans find hidden objects during a hiding-finding game. Found that children at both ages performed above chance with all signs. No ape performed above chance for any signs not known before the experiment despite three times as many…

  3. Comparative and Familial Analysis of Handedness in Great Apes

    ERIC Educational Resources Information Center

    Hopkins, William D.

    2006-01-01

    Historically, population-level handedness has been considered a hallmark of human evolution. Whether nonhuman primates exhibit population-level handedness remains a topic of considerable debate. This paper summarizes published data on handedness in great apes. Comparative analysis indicated that chimpanzees and bonobos show population-level right…

  4. Phylogenetic Approach to Object Manipulation in Human and Ape Infants.

    ERIC Educational Resources Information Center

    Vauclair, Jacques

    1984-01-01

    Parker and Gibson's developmental model of evolution of language and intelligence in early hominids is described and discussed; data from a comparative study of object manipulation in two apes and a human infant are reported; and, human ontogenic developmental retardation in locomotion is discussed in terms of its implications for the differential…

  5. Wild great apes as sentinels and sources of infectious disease.

    PubMed

    Calvignac-Spencer, S; Leendertz, S A J; Gillespie, T R; Leendertz, F H

    2012-06-01

    Emerging zoonotic infectious diseases pose a serious threat to global health. This is especially true in relation to the great apes, whose close phylogenetic relationship with humans results in a high potential for microorganism exchange. In this review, we show how studies of the microorganisms of wild great apes can lead to the discovery of novel pathogens of importance for humans. We also illustrate how these primates, living in their natural habitats, can serve as sentinels for outbreaks of human disease in regions with a high likelihood of disease emergence. Greater sampling efforts and improvements in sample preservation and diagnostic capacity are rapidly improving our understanding of the diversity and distribution of microorganisms in wild great apes. Linking non-invasive diagnostic data with observational health data from great apes habituated to human presence is a promising approach for the discovery of pathogens of high relevance for humans. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

  6. Monkeys and apes: are their cognitive skills really so different?

    PubMed

    Amici, Federica; Aureli, Filippo; Call, Josep

    2010-10-01

    Differences in cognitive skills across taxa, and between monkeys and apes in particular, have been explained by different hypotheses, although these often are not supported by systematic interspecific comparisons. Here, we directly compared the cognitive performance of the four great apes and three monkey species (spider monkeys, capuchin monkeys, and long-tailed macaques), differing in their phylogenetic-relatedness and socioecology. We tested subjects on their ability to remember object locations (memory task), track object displacements (transposition task), and obtain out-of-reach rewards (support task). Our results showed no support for an overall clear-cut distinction in cognitive skills between monkeys and apes as species performance varied substantially across tasks. Although we found differences in performance at tracking object displacements between monkeys and apes, interspecific differences in the other two tasks were better explained in terms of differential socioecology, especially differential levels of fission-fusion dynamics. A cluster analysis using mean scores of each condition of the three tasks for each species suggested that the only dichotomy might be between members of the genus Pan and the rest of the tested species. These findings evidence the importance of using multiple tasks across multiple species in a comparative perspective to test different explanations for the enhancement of specific cognitive skills. © 2010 Wiley-Liss, Inc.

  7. Pointing Behaviors in Apes and Human Infants: A Balanced Interpretation

    ERIC Educational Resources Information Center

    Gomez, Juan-Carlos

    2007-01-01

    This article presents a tentatively "balanced" view (i.e., midway between lean and rich interpretations) of pointing behavior in infants and apes, based upon the notion of intentional reading of behavior without simultaneous attribution of unobservable mental states. This can account for the complexity of infant pointing without attributing…

  8. Great apes infer others' goals based on context.

    PubMed

    Buttelmann, David; Schütte, Sebastian; Carpenter, Malinda; Call, Josep; Tomasello, Michael

    2012-11-01

    In previous studies claiming to demonstrate that great apes understand the goals of others, the apes could potentially have been using subtle behavioral cues present during the test to succeed. In the current studies, we ruled out the use of such cues by making the behavior of the experimenter identical in the test phase of both the experimental and control conditions; the only difference was the preceding "context." In the first study, apes interpreted a human's ambiguous action as having the underlying goal of opening a box, or not, based on that human's previous actions with similar boxes. In the second study, chimpanzees learned that when a human stood up she was going to go get food for them, but when a novel, unexpected event happened, they changed their expectation-presumably based on their understanding that this new event led the human to change her goal. These studies suggest that great apes do not need concurrent behavioral cues to infer others' goals, but can do so from a variety of different types of cues-even cues displaced in time.

  9. Comparative and Familial Analysis of Handedness in Great Apes

    ERIC Educational Resources Information Center

    Hopkins, William D.

    2006-01-01

    Historically, population-level handedness has been considered a hallmark of human evolution. Whether nonhuman primates exhibit population-level handedness remains a topic of considerable debate. This paper summarizes published data on handedness in great apes. Comparative analysis indicated that chimpanzees and bonobos show population-level right…

  10. Beyond eugenics: the forgotten scandal of hybridizing humans and apes.

    PubMed

    Etkind, Alexander

    2008-06-01

    This paper examines the available evidence on one of the most radical ideas in the history of eugenics and utopianism. In the mid-1920s, the zoology professor Ilia Ivanov submitted to the Soviet government a project for hybridizing humans and apes by means of artificial insemination. He received substantial financing and organized expeditions to Africa to catch apes for his experiments. His project caused an international sensation. The American Association for the Advancement of Atheism announced its fund-raising campaign to support Ivanov's project but gave it a scandalously racist interpretation. Ivanov's own motivation remained unclear, as did the motivation of those in the Bolshevik government who supported Ivanov until his arrest in 1930. This paper discusses three hypothetical reasons for Ivanov's adventure: first, hybridization between humans and apes, should it be successful, would support the atheist propaganda of the Bolsheviks; second, regardless of the success of hybridization, Ivanov would catch and bring to Russia apes, which were necessary for the rejuvenation programs that were fashionable among the Bolshevik elite; and third, hybridization, should it be successful, would pave the way to the New Socialist Man whose 'construction by scientific means' was the official purpose of the Bolsheviks. Ivanov's ideas were arguably important for the American proponent of reform eugenics, Herman Muller, and for the Soviet anthropologist Boris Porshnev.

  11. Pointing Behaviors in Apes and Human Infants: A Balanced Interpretation

    ERIC Educational Resources Information Center

    Gomez, Juan-Carlos

    2007-01-01

    This article presents a tentatively "balanced" view (i.e., midway between lean and rich interpretations) of pointing behavior in infants and apes, based upon the notion of intentional reading of behavior without simultaneous attribution of unobservable mental states. This can account for the complexity of infant pointing without attributing…

  12. Foresight, function representation, and social intelligence in the great apes.

    PubMed

    Osvath, Mathias; Persson, Tomas; Gärdenfors, Peter

    2012-08-01

    We find problems with Vaesen's treatment of the primatological research, in particular his analysis of foresight, function representation, and social intelligence. We argue that his criticism of research on foresight in great apes is misguided. His claim that primates do not attach functions to particular objects is also problematic. Finally, his analysis of theory of mind neglects many distinctions.

  13. The aquatic ape theory and some common diseases.

    PubMed

    Verhaegen, M J

    1987-11-01

    The Aquatic Ape Theory claims that human ancestors once lived in a semi-aquatic habitat. Some human diseases might be explained by our aquatic past. Such problems include hyperventilation, periodic breathing, laryngo- and bronchospasm, vasomotor rhinopathy, seborrhea, dandruff, male pattern alopecia, rhinophyma, osteoarthritis, inguinal hernias, varicose veins, common obesity, myopia, and ear-wax.

  14. Peroxiredoxin 1 interacts with and blocks the redox factor APE1 from activating interleukin-8 expression

    PubMed Central

    Nassour, Hassan; Wang, Zhiqiang; Saad, Amine; Papaluca, Arturo; Brosseau, Nicolas; Affar, El Bachir; Alaoui-Jamali, Moulay A.; Ramotar, Dindial

    2016-01-01

    APE1 is an essential DNA repair protein that also possesses the ability to regulate transcription. It has a unique cysteine residue C65, which maintains the reduce state of several transcriptional activators such as NF-κB. How APE1 is being recruited to execute the various biological functions remains unknown. Herein, we show that APE1 interacts with a novel partner PRDX1, a peroxidase that can also prevent oxidative damage to proteins by serving as a chaperone. PRDX1 knockdown did not interfere with APE1 expression level or its DNA repair activities. However, PRDX1 knockdown greatly facilitates APE1 detection within the nucleus by indirect immunofluorescence analysis, even though APE1 level was unchanged. The loss of APE1 interaction with PRDX1 promotes APE1 redox function to activate binding of the transcription factor NF-κB onto the promoter of a target gene, the proinflammatory chemokine IL-8 involved in cancer invasion and metastasis, resulting in its upregulation. Depletion of APE1 blocked the upregulation of IL-8 in the PRDX1 knockdown cells. Our findings suggest that the interaction of PRDX1 with APE1 represents a novel anti-inflammatory function of PRDX1, whereby the association safeguards APE1 from reducing transcription factors and activating superfluous gene expression, which otherwise could trigger cancer invasion and metastasis. PMID:27388124

  15. Histone deacetylases inhibitor trichostatin A modulates the extracellular release of APE1/Ref-1

    SciTech Connect

    Choi, Sunga; Lee, Yu Ran; Park, Myoung Soo; Joo, Hee Kyoung; Cho, Eun Jung; Kim, Hyo Shin; Kim, Cuk Seong; Park, Jin Bong; Irani, Kaikobad; Jeon, Byeong Hwa

    2013-06-07

    Highlights: •Trichostatin A (TSA) increased APE1/Ref-1 secretion in HEK293 cells. •Lysine-mutated APE1/Ref-1 (K6R/K7R) was not secreted by TSA. •TSA induced cytoplasmic translocation of APE1/Ref-1. •APE1/Ref-1 is a protein whose secretion is governed by lysine acetylation. -- Abstract: Apurinic/apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) can be acetylated via post-translational modification. We investigated the effect of an inhibitor of histone deacetylases on the extracellular release of APE1/Ref-1 in HEK293 cells. Trichostatin A (TSA), an inhibitor of histone deacetylases, induced APE1/Ref-1 secretion without changing cell viability. In a fluorescence quantitative assay, the secreted APE1/Ref-1 was estimated to be about 10 ng/mL in response to TSA (1 μM). However, TSA did not induce the secretion of lysine-mutated APE1/Ref-1 (K6R/K7R). TSA also caused nuclear to cytoplasmic translocation of APE1/Ref-1. Taken together, these findings suggest that APE1/Ref-1 is a protein whose secretion is governed by lysine acetylation.

  16. The Time Scale of Recombination Rate Evolution in Great Apes.

    PubMed

    Stevison, Laurie S; Woerner, August E; Kidd, Jeffrey M; Kelley, Joanna L; Veeramah, Krishna R; McManus, Kimberly F; Bustamante, Carlos D; Hammer, Michael F; Wall, Jeffrey D

    2016-04-01

    We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471-475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10-15 Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- and between-species genome-wide recombination rate variation in several close relatives.

  17. Unexplored Archaeal Diversity in the Great Ape Gut Microbiome

    PubMed Central

    Moeller, Andrew H.; Goodman, Andrew L.; Ochman, Howard

    2017-01-01

    ABSTRACT Archaea are habitual residents of the human gut flora but are detected at substantially lower frequencies than bacteria. Previous studies have indicated that each human harbors very few archaeal species. However, the low diversity of human-associated archaea that has been detected could be due to the preponderance of bacteria in these communities, such that relatively few sequences are classified as Archaea even when microbiomes are sampled deeply. Moreover, the universal prokaryotic primer pair typically used to interrogate microbial diversity has low specificity to the archaeal domain, potentially leaving vast amounts of diversity unobserved. As a result, the prevalence, diversity, and distribution of archaea may be substantially underestimated. Here we evaluate archaeal diversity in gut microbiomes using an approach that targets virtually all known members of this domain. Comparing microbiomes across five great ape species allowed us to examine the dynamics of archaeal lineages over evolutionary time scales. These analyses revealed hundreds of gut-associated archaeal lineages, indicating that upwards of 90% of the archaeal diversity in the human and great ape gut microbiomes has been overlooked. Additionally, these results indicate a progressive reduction in archaeal diversity in the human lineage, paralleling the decline reported for bacteria. IMPORTANCE Our findings show that Archaea are a habitual and vital component of human and great ape gut microbiomes but are largely ignored on account of the failure of previous studies to realize their full diversity. Here we report unprecedented levels of archaeal diversity in great ape gut microbiomes, exceeding that detected by conventional 16S rRNA gene surveys. Paralleling what has been reported for bacteria, there is a vast reduction of archaeal diversity in humans. Our study demonstrates that archaeal diversity in the great ape gut microbiome greatly exceeds that reported previously and provides the basis

  18. Unexplored Archaeal Diversity in the Great Ape Gut Microbiome.

    PubMed

    Raymann, Kasie; Moeller, Andrew H; Goodman, Andrew L; Ochman, Howard

    2017-01-01

    Archaea are habitual residents of the human gut flora but are detected at substantially lower frequencies than bacteria. Previous studies have indicated that each human harbors very few archaeal species. However, the low diversity of human-associated archaea that has been detected could be due to the preponderance of bacteria in these communities, such that relatively few sequences are classified as Archaea even when microbiomes are sampled deeply. Moreover, the universal prokaryotic primer pair typically used to interrogate microbial diversity has low specificity to the archaeal domain, potentially leaving vast amounts of diversity unobserved. As a result, the prevalence, diversity, and distribution of archaea may be substantially underestimated. Here we evaluate archaeal diversity in gut microbiomes using an approach that targets virtually all known members of this domain. Comparing microbiomes across five great ape species allowed us to examine the dynamics of archaeal lineages over evolutionary time scales. These analyses revealed hundreds of gut-associated archaeal lineages, indicating that upwards of 90% of the archaeal diversity in the human and great ape gut microbiomes has been overlooked. Additionally, these results indicate a progressive reduction in archaeal diversity in the human lineage, paralleling the decline reported for bacteria. IMPORTANCE Our findings show that Archaea are a habitual and vital component of human and great ape gut microbiomes but are largely ignored on account of the failure of previous studies to realize their full diversity. Here we report unprecedented levels of archaeal diversity in great ape gut microbiomes, exceeding that detected by conventional 16S rRNA gene surveys. Paralleling what has been reported for bacteria, there is a vast reduction of archaeal diversity in humans. Our study demonstrates that archaeal diversity in the great ape gut microbiome greatly exceeds that reported previously and provides the basis for

  19. [Construction and identification of a multiple myeloma-specific APE1 siRNA expression vector].

    PubMed

    Yang, Zhen-zhou; Chen, Xing-hua; Wang, Dong; Wang, Ge; Xiang, De-bing

    2006-04-01

    To construct a multiple myeloma (MM)-specific APE1siRNA expression vector, and detect the specific knock-down effect of the siRNA on expression of APE1 protein. APE1siRNA cDNA sequence was designed, synthesized and inserted into pSilencer 2.0-U6 linear expression vector. pSilencer APE1siRNA was digested by enzyme EcoRI and BamHI, then linear vector and IgP fragments were conjugated by T4 DNA ligase. pSilencer IgP-APE1siRNA and pSilencer IE-IgP-APE1siRNA were digested by enzyme EcoRI or XhoI. Linear vector and IE or Kappa fragments were conjugated by T4 DNA ligase. Then a MM specific pSilencer K-IE-IgP-APE1siRNA was cloned. The recombinant products were identified by DNA sequencing and enzyme digestions at each step. pSilencer K-IE-IgP-APE1siRNA plasmid was transfected to KM3, HOS, MDA-231 cells by liposome. APE1 gene silence induced by RNAi was analysed by Western blot. APE1 protein in KM3 cells could be knocked down effectively and specifically by pSilencer K-IE-IgP-APE1siRNA vector. After 2 days, the level of APE1 protein in KM3 cells transfected with siRNA was 0.118 +/- 0.047, while that transfected with plasmid only was 0.988 +/- 0.029. The efficiency of gene silence was 90%. A MM specific APE1siRNA expression vector was successfully constructed.

  20. Gibbon genome and the fast karyotype evolution of small apes.

    PubMed

    Carbone, Lucia; Harris, R Alan; Gnerre, Sante; Veeramah, Krishna R; Lorente-Galdos, Belen; Huddleston, John; Meyer, Thomas J; Herrero, Javier; Roos, Christian; Aken, Bronwen; Anaclerio, Fabio; Archidiacono, Nicoletta; Baker, Carl; Barrell, Daniel; Batzer, Mark A; Beal, Kathryn; Blancher, Antoine; Bohrson, Craig L; Brameier, Markus; Campbell, Michael S; Capozzi, Oronzo; Casola, Claudio; Chiatante, Giorgia; Cree, Andrew; Damert, Annette; de Jong, Pieter J; Dumas, Laura; Fernandez-Callejo, Marcos; Flicek, Paul; Fuchs, Nina V; Gut, Ivo; Gut, Marta; Hahn, Matthew W; Hernandez-Rodriguez, Jessica; Hillier, LaDeana W; Hubley, Robert; Ianc, Bianca; Izsvák, Zsuzsanna; Jablonski, Nina G; Johnstone, Laurel M; Karimpour-Fard, Anis; Konkel, Miriam K; Kostka, Dennis; Lazar, Nathan H; Lee, Sandra L; Lewis, Lora R; Liu, Yue; Locke, Devin P; Mallick, Swapan; Mendez, Fernando L; Muffato, Matthieu; Nazareth, Lynne V; Nevonen, Kimberly A; O'Bleness, Majesta; Ochis, Cornelia; Odom, Duncan T; Pollard, Katherine S; Quilez, Javier; Reich, David; Rocchi, Mariano; Schumann, Gerald G; Searle, Stephen; Sikela, James M; Skollar, Gabriella; Smit, Arian; Sonmez, Kemal; ten Hallers, Boudewijn; Terhune, Elizabeth; Thomas, Gregg W C; Ullmer, Brygg; Ventura, Mario; Walker, Jerilyn A; Wall, Jeffrey D; Walter, Lutz; Ward, Michelle C; Wheelan, Sarah J; Whelan, Christopher W; White, Simon; Wilhelm, Larry J; Woerner, August E; Yandell, Mark; Zhu, Baoli; Hammer, Michael F; Marques-Bonet, Tomas; Eichler, Evan E; Fulton, Lucinda; Fronick, Catrina; Muzny, Donna M; Warren, Wesley C; Worley, Kim C; Rogers, Jeffrey; Wilson, Richard K; Gibbs, Richard A

    2014-09-11

    Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ∼5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat.

  1. Gibbon genome and the fast karyotype evolution of small apes

    PubMed Central

    Carbone, Lucia; Harris, R. Alan; Gnerre, Sante; Veeramah, Krishna R.; Lorente-Galdos, Belen; Huddleston, John; Meyer, Thomas J.; Herrero, Javier; Roos, Christian; Aken, Bronwen; Anaclerio, Fabio; Archidiacono, Nicoletta; Baker, Carl; Barrell, Daniel; Batzer, Mark A.; Beal, Kathryn; Blancher, Antoine; Bohrson, Craig L.; Brameier, Markus; Campbell, Michael S.; Capozzi, Oronzo; Casola, Claudio; Chiatante, Giorgia; Cree, Andrew; Damert, Annette; de Jong, Pieter J.; Dumas, Laura; Fernandez-Callejo, Marcos; Flicek, Paul; Fuchs, Nina V.; Gut, Marta; Gut, Ivo; Hahn, Matthew W.; Hernandez-Rodriguez, Jessica; Hillier, LaDeana W.; Hubley, Robert; Ianc, Bianca; Izsvák, Zsuzsanna; Jablonski, Nina G.; Johnstone, Laurel M.; Karimpour-Fard, Anis; Konkel, Miriam K.; Kostka, Dennis; Lazar, Nathan H.; Lee, Sandra L.; Lewis, Lora R.; Liu, Yue; Locke, Devin P.; Mallick, Swapan; Mendez, Fernando L.; Muffato, Matthieu; Nazareth, Lynne V.; Nevonen, Kimberly A.; O,Bleness, Majesta; Ochis, Cornelia; Odom, Duncan T.; Pollard, Katherine S.; Quilez, Javier; Reich, David; Rocchi, Mariano; Schumann, Gerald G.; Searle, Stephen; Sikela, James M.; Skollar, Gabriella; Smit, Arian; Sonmez, Kemal; Hallers, Boudewijn ten; Terhune, Elizabeth; Thomas, Gregg W.C.; Ullmer, Brygg; Ventura, Mario; Walker, Jerilyn A.; Wall, Jeffrey D.; Walter, Lutz; Ward, Michelle C.; Wheelan, Sarah J.; Whelan, Christopher W.; White, Simon; Wilhelm, Larry J.; Woerner, August E.; Yandell, Mark; Zhu, Baoli; Hammer, Michael F.; Marques-Bonet, Tomas; Eichler, Evan E.; Fulton, Lucinda; Fronick, Catrina; Muzny, Donna M.; Warren, Wesley C.; Worley, Kim C.; Rogers, Jeffrey; Wilson, Richard K.; Gibbs, Richard A.

    2014-01-01

    Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ~5 million years ago, coincident with major geographical changes in Southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat. PMID:25209798

  2. Ape parasite origins of human malaria virulence genes

    PubMed Central

    Larremore, Daniel B.; Sundararaman, Sesh A.; Liu, Weimin; Proto, William R.; Clauset, Aaron; Loy, Dorothy E.; Speede, Sheri; Plenderleith, Lindsey J.; Sharp, Paul M.; Hahn, Beatrice H.; Rayner, Julian C.; Buckee, Caroline O.

    2015-01-01

    Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum. PMID:26456841

  3. The influence of fallback foods on great ape tooth enamel.

    PubMed

    Constantino, Paul J; Lucas, Peter W; Lee, James J-W; Lawn, Brian R

    2009-12-01

    Lucas and colleagues recently proposed a model based on fracture and deformation concepts to describe how mammalian tooth enamel may be adapted to the mechanical demands of diet (Lucas et al.: Bioessays 30 2008 374-385). Here we review the applicability of that model by examining existing data on the food mechanical properties and enamel morphology of great apes (Pan, Pongo, and Gorilla). Particular attention is paid to whether the consumption of fallback foods is likely to play a key role in influencing great ape enamel morphology. Our results suggest that this is indeed the case. We also consider the implications of this conclusion on the evolution of the dentition of extinct hominins.

  4. Simian Foamy Virus Transmission from Apes to Humans, Rural Cameroon

    PubMed Central

    Calattini, Sara; Betsem, Edouard B.A.; Froment, Alain; Mauclère, Philippe; Tortevoye, Patricia; Schmitt, Christine; Njouom, Richard; Saib, Ali

    2007-01-01

    Simian virus infections of humans are an increasing public health concern. Simian foamy virus (SFV) infections have been reported in persons occupationally exposed to nonhuman primates and in a few hunters in Cameroon. To better understand this retroviral zoonosis in natural settings, we studied persons who lived in southern Cameroon, near nonhuman primate habitats. First we studied a general population of 1,164 adults; 4 were SFV positive according to serologic and molecular assays. Then we studied 85 persons who reported having been bitten or scratched by nonhuman primates; 7/29 (24.1%) of those who had contact with apes (gorillas or chimpanzees) were SFV positive, compared with only 2/56 (3.6%) of those who had had contact with monkeys. These data demonstrate efficient transmission of SFVs to humans in natural settings in central Africa, specifically following ape bites, and viral persistence in the human host. PMID:18252101

  5. Reconstructing the evolution of laughter in great apes and humans.

    PubMed

    Davila Ross, Marina; Owren, Michael J; Zimmermann, Elke

    2009-07-14

    Human emotional expressions, such as laughter, are argued to have their origins in ancestral nonhuman primate displays. To test this hypothesis, the current work examined the acoustics of tickle-induced vocalizations from infant and juvenile orangutans, gorillas, chimpanzees, and bonobos, as well as tickle-induced laughter produced by human infants. Resulting acoustic data were then coded as character states and submitted to quantitative phylogenetic analysis. Acoustic outcomes revealed both important similarities and differences among the five species. Furthermore, phylogenetic trees reconstructed from the acoustic data matched the well-established trees based on comparative genetics. Taken together, the results provide strong evidence that tickling-induced laughter is homologous in great apes and humans and support the more general postulation of phylogenetic continuity from nonhuman displays to human emotional expressions. Findings also show that distinctively human laughter characteristics such as predominantly regular, stable voicing and consistently egressive airflow are nonetheless traceable to characteristics of shared ancestors with great apes.

  6. Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation.

    PubMed

    Stavnezer, Janet; Linehan, Erin K; Thompson, Mikayla R; Habboub, Ghaith; Ucher, Anna J; Kadungure, Tatenda; Tsuchimoto, Daisuke; Nakabeppu, Yusaku; Schrader, Carol E

    2014-06-24

    Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase β. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells.

  7. Morphological variation in great ape and modern human mandibles

    PubMed Central

    HUMPHREY, L. T.; DEAN, M. C.; STRINGER, C. B.

    1999-01-01

    Adult mandibles of 317 modern humans and 91 great apes were selected that showed no pathology. Adult mandibles of Pan troglodytes troglodytes, Pongo pygmaeus pygmaeus and Gorilla gorilla gorilla and from 2 modern human populations (Zulu and Europeans from Spitalfields) were reliably sexed. Thirteen measurements were defined and included mandibular height, length and breadth in representative positions. Univariate statistical techniques and multivariate (principal component analysis and discriminant analysis) statistical techniques were used to investigate interspecific variability and sexual dimorphism in human and great ape mandibles, and intraspecific variability among the modern human mandibles. Analysis of interspecific differences revealed some pairs of variables with a tight linear relationship and others where Homo and the great apes pulled apart from one another due to shape differences. Homo and Pan are least sexually dimorphic in the mandible, Pan less so than Homo sapiens, but both the magnitude of sexual dimorphism and the distribution of sexually dimorphic measurements varied both among and between modern humans and great apes. Intraspecific variation among the 10 populations of modern humans was less than that generally reported in studies of crania (74.3% of mandibles were correctly classified into 1 of 10 populations using discriminant functions based on 13 variables as compared with 93% of crania from 17 populations based on 70 variables in one extensive study of crania). A subrecent European population (Poundbury) emerged as more different from a recent European population (Spitalfields) than other more diverse modern populations were from each other, suggesting considerable morphological plasticity in the mandible through time. This study forms a sound basis on which to explore mandibular variation in Neanderthals, early Homo sapiens and other more ancient fossil hominids. PMID:10634689

  8. Apes perform like infants in false-belief tasks.

    PubMed

    Bugnyar, Thomas

    2017-04-07

    Although the extent to which some nonhuman animals understand mental states is currently under debate, attributing false beliefs has been considered to be beyond their limits. A recent study by Krupenye, Kano, Hirata, Call, and Tomasello (Science, 354, 110-114, 2016) shows that great apes pass a false-belief task when they are tested with an anticipatory-looking paradigm developed for nonverbal human infants.

  9. The Relationship of African Apes, Man, and Old World Monkeys

    PubMed Central

    Leakey, L. S. B.

    1970-01-01

    The conclusions of Wilson and Sarich (Proc. Nat. Acad. Sci. USA, 63, 1088-1093 (1969) that the human lineage diverged from that leading to the African apes about 4 to 5 million years ago is shown to be based upon a wholly unsupported assumption that the Superfamilies Hominoidea and Cercopithecoidea only separated from each other some 30 million years ago. This is entirely contrary to most recent palaeontological evidence. PMID:5002096

  10. Sexual dimorphism in canine shape among extant great apes.

    PubMed

    Kelley, J

    1995-04-01

    There have been numerous attempts to sex fossil specimens using the canine dentition. Whether focused on canine size or canine shape, most of these efforts share two deficiencies: lack of quantification of male-female differences in the adopted criteria and a failure to adequately explore among extant species the discriminatory power of these criteria. Here, canine shape indices relating to relative canine height, upper canine root/crown proportionality, and relative length of the lower canine mesial ridge were calculated for males and females of all species and subspecies of extant great apes and two species of gibbons. The accuracy of these indices for identifying the sex of the extant ape specimens was investigated through discriminant analysis and the use of bivariate plots of the two upper and two lower canine indices. The indices were found to be highly accurate in identifying the sex of great ape individuals, not only in single-species and subspecies samples but in mixed-species samples as well; assignment error rates were mostly between 0 and 4%. Accuracy was lowest in Pan (error rates as high as 15%) and highest in Pongo (one error). In most cases, error rates were lower in the upper canines. The effectiveness of these shape indices for sexing might be related to the degree of absolute canine size dimorphism; the indices did not effectively segregate males and females among minimally canine-dimorphic gibbons. The mixed-species results reveal that same-sex index values are remarkably concordant across great ape species, as are the patterns of spatial segregation of males and females in the bivariate plots. Results suggest that, while the indices can be used with some confidence to sex individual fossil specimens, their greatest utility will be for identifying the sex of groups of canines united by size and morphology.

  11. South to south learning in great ape conservation.

    PubMed

    Schoneveld-de Lange, Nicolien; Meijaard, Erik; Löhr, Ansje

    2016-06-01

    Despite evidence that killing of Bornean Orangutan (Pongo pygmaeus) in South-East Asia is a major threat to the species, few researchers and non-governmental conservationists have addressed it in management and research, and there is virtually no implementation of anti-killing strategies. In large parts of the Congo Basin, Central Africa, instead, illegal killing of great apes is acknowledged to be their largest threat, and many conservation strategies have been used to reduce killing pressure. However, since these strategies have not been subject to systematic and comprehensive review, it remains unclear which of them have been successful and why. Knowledge of the success, failure, and practices of common conservation strategies to manage great ape killing is critical to ensure adaptive conservation management in the Congo Basin. Understanding the Congo context also facilitates simultaneously highlighting great ape killing in Borneo and suggesting solutions to manage orangutan killing. Here, we compile and analyze the available literature on great ape conservation strategies for reducing killing rates in the Congo Basin. Through a systematic literature review of 198 publications, we find that the most widely employed conservation strategies in the Congo Basin are legislation and law enforcement, protected area management, community-based conservation, alternatives to bushmeat consumption and trade, ecotourism, education, and capacity building. Despite lack of rigorous post-intervention evaluation of conservation impact, we derive several recommendations for addressing the orangutan killing issue in Borneo. A critical lesson, widely applicable to developing countries for conservationists and not limited to Congo Basin realities, is the need for rigorous post-intervention evaluations compared to pre-intervention baselines and over appropriate time frames. Am. J. Primatol. 78:669-678, 2016. © 2016 Wiley Periodicals, Inc.

  12. The femur of Orrorin tugenensis exhibits morphometric affinities with both Miocene apes and later hominins.

    PubMed

    Almécija, Sergio; Tallman, Melissa; Alba, David M; Pina, Marta; Moyà-Solà, Salvador; Jungers, William L

    2013-01-01

    Orrorin tugenensis (Kenya, ca. 6 Ma) is one of the earliest putative hominins. Its proximal femur, BAR 1002'00, was originally described as being very human-like, although later multivariate analyses showed an australopith pattern. However, some of its traits (for example, laterally protruding greater trochanter, medially oriented lesser trochanter and presence of third trochanter) are also present in earlier Miocene apes. Here, we use geometric morphometrics to reassess the morphological affinities of BAR 1002'00 within a large sample of anthropoids (including fossil apes and hominins) and reconstruct hominoid proximal femur evolution using squared-change parsimony. Our results indicate that both hominin and modern great ape femora evolved in different directions from a primitive morphology represented by some fossil apes. Orrorin appears intermediate between Miocene apes and australopiths in shape space. This evidence is consistent with femoral shape similarities in extant great apes being derived and homoplastic and has profound implications for understanding the origins of human bipedalism.

  13. Communication about absent entities in great apes and human infants.

    PubMed

    Bohn, Manuel; Call, Josep; Tomasello, Michael

    2015-12-01

    There is currently debate about the extent to which non-linguistic beings such as human infants and great apes are capable of absent reference. In a series of experiments we investigated the flexibility and specificity of great apes' (N=36) and 12 month-old infants' (N=40) requests for absent entities. Subjects had the choice between requesting visible objects directly and using the former location of a depleted option to request more of these now-absent entities. Importantly, we systematically varied the quality of the present and absent options. We found that great apes as well as human infants flexibly adjusted their requests for absent entities to these contextual variations and only requested absent entities when the visible option was of lower quality than the absent option. These results suggest that the most basic cognitive capacities for absent reference do not depend on language and are shared by humans and their closest living relatives. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Unique human orbital morphology compared with that of apes.

    PubMed

    Denion, Eric; Hitier, Martin; Guyader, Vincent; Dugué, Audrey-Emmanuelle; Mouriaux, Frédéric

    2015-06-25

    Humans' and apes' convergent (front-facing) orbits allow a large overlap of monocular visual fields but are considered to limit the lateral visual field extent. However, humans can greatly expand their lateral visual fields using eye motion. This study aimed to assess whether the human orbital morphology was unique compared with that of apes in avoiding lateral visual field obstruction. The orbits of 100 human skulls and 120 ape skulls (30 gibbons; 30 orangutans; 30 gorillas; 30 chimpanzees and bonobos) were analyzed. The orbital width/height ratio was calculated. Two orbital angles representing orbital convergence and rearward position of the orbital margin respectively were recorded using a protractor and laser levels. Humans have the largest orbital width/height ratio (1.19; p < 0.001). Humans and gibbons have orbits which are significantly less convergent than those of chimpanzees/bonobos, gorillas and orangutans (p < 0.001). These elements suggest a morphology favoring lateral vision in humans. More specifically, the human orbit has a uniquely rearward temporal orbital margin (107.1°; p < 0.001), suitable for avoiding visual obstruction and promoting lateral visual field expansion through eye motion. Such an orbital morphology may have evolved mainly as an adaptation to open-country habitat and bipedal locomotion.

  15. The evolution of laughter in great apes and humans

    PubMed Central

    Owren, Michael J; Zimmermann, Elke

    2010-01-01

    It has long been claimed that human emotional expressions, such as laughter, have evolved from nonhuman displays. The aim of the current study was to test this prediction by conducting acoustic and phylogenetic analyses based on the acoustics of tickle-induced vocalizations of orangutans, gorillas, chimpanzees, bonobos and humans. Results revealed both important similarities and differences among the various species’ vocalizations, with the phylogenetic tree reconstructed based on these acoustic data matching the well-established genetic relationships of great apes and humans. These outcomes provide evidence of a common phylogenetic origin of tickle-induced vocalizations in these taxa, which can therefore be termed “laughter” across all five species. Results are consistent with the claims of phylogenetic continuity of emotional expressions. Together with observations made on the use of laughter in great apes and humans, findings of this study further indicate that there were two main periods of selection-driven evolutionary change in laughter within the Hominidae, to a smaller degree, among the great apes and, most distinctively, after the separation of hominins from the last common ancestor with chimpanzees and bonobos. PMID:20585520

  16. No Evidence for Ape Plasmodium Infections in Humans in Gabon

    PubMed Central

    Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M.; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck

    2015-01-01

    African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife. PMID:26039338

  17. No evidence for ape Plasmodium infections in humans in Gabon.

    PubMed

    Délicat-Loembet, Lucresse; Rougeron, Virginie; Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck

    2015-01-01

    African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife.

  18. The evolution of laughter in great apes and humans.

    PubMed

    Ross, Marina Davila; Owren, Michael J; Zimmermann, Elke

    2010-03-01

    It has long been claimed that human emotional expressions, such as laughter, have evolved from nonhuman displays. The aim of the current study was to test this prediction by conducting acoustic and phylogenetic analyses based on the acoustics of tickle-induced vocalizations of orangutans, gorillas, chimpanzees, bonobos and humans. Results revealed both important similarities and differences among the various species' vocalizations, with the phylogenetic tree reconstructed based on these acoustic data matching the well-established genetic relationships of great apes and humans. These outcomes provide evidence of a common phylogenetic origin of tickle-induced vocalizations in these taxa, which can therefore be termed "laughter" across all five species. Results are consistent with the claims of phylogenetic continuity of emotional expressions. Together with observations made on the use of laughter in great apes and humans, findings of this study further indicate that there were two main periods of selection-driven evolutionary change in laughter within the Hominidae, to a smaller degree, among the great apes and, most distinctively, after the separation of hominins from the last common ancestor with chimpanzees and bonobos.

  19. Clinical and pathologic manifestation of oesophagostomosis in African great apes: does self-medication in wild apes influence disease progression?

    PubMed

    Krief, Sabrina; Jamart, Aliette; Mahé, Sandrine; Leendertz, Fabian H; Mätz-Rensing, Kerstin; Crespeau, François; Bain, Odile; Guillot, Jacques

    2008-08-01

    Nodular worms (Oesophagostomum spp.) are common intestinal parasites found in cattle, pig, and primates including humans. In human, they are responsible for serious clinical disease called oesophagostomosis resulting from the formation of granulomas, caseous lesions or abscesses in intestinal walls. In wild great apes, the fecal prevalence of this parasite is high, but little information is available concerning the clinical signs and lesions associated. In the present study, we describe six cases of multinodular oesophagostomosis in free-ranging and ex-captive chimpanzees and captive gorillas caused by Oesophagostomum stephanostomum. While severe clinical signs associated with this infection were observed in great apes raised in sanctuaries, nodules found in wild chimpanzees do not seem to affect their health status. One hypothesis to explain this difference would be that in wild chimpanzees, access to natural environment and behavior such as rough leaves swallowing combined with ingestion of plants having pharmacological properties would prevent severe infection and decrease potential symptoms.

  20. Reducing the neural search space for hominid cognition: what distinguishes human and great ape brains from those of small apes?

    PubMed

    Butler, David; Suddendorf, Thomas

    2014-06-01

    Differences in the psychological capacities of closely related species are likely due to differences in their brains. Here, we review neuroanatomical comparisons between hominids (i.e., great apes and humans) and their closest living relatives, the hylobatids (i.e., small apes). We report the differences in quantitative, as well as qualitative, neural characteristics on the basis of 19 comparative studies that each included representatives of all hominid genera and at least one genus of hylobatid. The current data are patchy, based on a small number of hylobatids and few neuroanatomical features. Yet a systematic interspecies comparison could help reduce the neuroanatomical search space for the neural correlates underlying psychological abilities restricted to hominids. We illustrate the potential power of this approach by discussing the neural features of visual self-recognition.

  1. Non-goal-directed recall of specific events in apes after long delays.

    PubMed

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-07-12

    We examined if apes spontaneously remember one-time, distinctive events across long delays when probed by discriminant cues. Apes witnessed an experimenter hide a cache of food, which they could then retrieve. They retrieved one of two food types; one more distinctive than the other. Two, 10 or 50 weeks later, the apes returned to the same enclosure and found a piece of the previously hidden food on the ground. An experimenter who had not hidden the food was also present. Apes immediately searched the location where the food was previously hidden (no food was here), showing recall of the event. One week later, apes returned to the same enclosure, with the same food on the ground, but now the experimenter that had hidden the food was present. Again, apes immediately searched the hiding location. Apes that had not witnessed the hiding event did not search. There was no significant effect of food type, and retention declined from exposure to the two-week delay, then levelled, consistent with the forgetting curve in humans (Ebbinghaus, H. 1964 Memory: a contribution to experimental psychology (transl. H.A. Ruger & C.E. Bussenvis). New York, NY: Dover. (Original work published 1885.)). This is the first study to show apes can recall a one-time, non-goal-directed event longer than two weeks ago and that apes' recall declines in accordance with a standard retention function. © 2017 The Author(s).

  2. Differences in the early cognitive development of children and great apes.

    PubMed

    Wobber, Victoria; Herrmann, Esther; Hare, Brian; Wrangham, Richard; Tomasello, Michael

    2014-04-01

    There is very little research comparing great ape and human cognition developmentally. In the current studies we compared a cross-sectional sample of 2- to 4-year-old human children (n=48) with a large sample of chimpanzees and bonobos in the same age range (n=42, hereafter: apes) on a broad array of cognitive tasks. We then followed a group of juvenile apes (n=44) longitudinally over 3 years to track their cognitive development in greater detail. In skills of physical cognition (space, causality, quantities), children and apes performed comparably at 2 years of age, but by 4 years of age children were more advanced (whereas apes stayed at their 2-year-old performance levels). In skills of social cognition (communication, social learning, theory of mind), children out-performed apes already at 2 years, and increased this difference even more by 4 years. Patterns of development differed more between children and apes in the social domain than the physical domain, with support for these patterns present in both the cross-sectional and longitudinal ape data sets. These results indicate key differences in the pattern and pace of cognitive development between humans and other apes, particularly in the early emergence of specific social cognitive capacities in humans. Copyright © 2013 Wiley Periodicals, Inc.

  3. Pilot-In-The-Loop Evaluation of the Approach Procedures Expert System (APES)

    DTIC Science & Technology

    1997-07-30

    Expert System (APES), to support the pilot’s use of electronic approach plates in flying instrument approaches. This report describes the APES decision aid and the methodology and results of the Vehicle-Pilot Integration Branch’s pilot-in-the-loop evaluation of the APES. The objectives of the study were to assess: (1) the effectiveness of APES for supporting approach tasks, (2) the performance of the decision aid and (3) the useability of the pilot-vehicle interface. To accomplish study objectives, 16 pilots flew a series of instrument approaches in a cockpit

  4. Piagetian liquid conservation in the great apes (Pan paniscus, Pan troglodytes, and Pongo pygmaeus).

    PubMed

    Suda, Chikako; Call, Josep

    2004-09-01

    An understanding of Piagetian liquid conservation was investigated in 4 bonobos (Pan paniscus), 5 chimpanzees (Pan troglodytes), and 5 orangutans (Pongo pygmaeus). The apes were tested in the ability to track the larger of 2 quantities of juice that had undergone various kinds of transformations. The accuracy of the apes' judgment depended on the shape or number of containers into which the larger quantity was transferred. The apes made their choice mainly on the basis of visual estimation but showed modest success when the quantities were occluded. The results suggest that the apes rely to a greater extent on visual information, although they might have some appreciation of the constancy of liquid quantities.

  5. Regulation of limited N-terminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation

    PubMed Central

    Bhakat, Kishor K.; Sengupta, Shiladitya; Adeniyi, Victor F.; Roychoudhury, Shrabasti; Nath, Somsubhra; Bellot, Larry J.; Feng, Dan; Mantha, Anil K.; Sinha, Mala; Qiu, Suimin; Luxon, Bruce A.

    2016-01-01

    Mammalian apurinic/apyrimidinic (AP) endonuclease 1 (APE1), a ubiquitous and multifunctional protein, plays an essential role in the repair of both endogenous and drug-induced DNA damages in the genome. Unlike its E.coli counterpart Xth, mammalian APE1 has a unique N-terminal domain and possesses both DNA damage repair and transcriptional regulatory functions. Although the overexpression of APE1 in diverse cancer types and the association of APE1 expression with chemotherapy resistance and poor prognosis are well documented, the cellular and molecular mechanisms that alter APE1 functions during tumorigenesis are largely unknown. Here, we show the presence of full-length APE1 and N-terminal truncated isoforms of APE1 in tumor tissue samples of various cancer types. However, primary tumor tissue has higher levels of acetylated APE1 (AcAPE1) as well as full-length APE1 compared to adjacent non-tumor tissue. We found that APE1 is proteolytically cleaved by an unknown serine protease at its N-terminus following residue lysine (Lys) Lys6 and/or Lys7 and after Lys27 and Lys31 or Lys32. Acetylation of these Lys residues in APE1 prevents this proteolysis. The N-terminal domain of APE1 and its acetylation are required for modulation of the expression of hundreds of genes. Importantly, we found that AcAPE1 is essential for sustained cell proliferation. Together, our study demonstrates that increased acetylation levels of APE1 in tumor cells inhibit the limited N-terminal proteolysis of APE1 and thereby maintain the functions of APE1 to promote tumor cells' sustained proliferation and survival. PMID:26981776

  6. Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1)

    PubMed Central

    Jackson, Elias B.; Theriot, Corey A.; Chattopadhyay, Ranajoy; Mitra, Sankar; Izumi, Tadahide

    2005-01-01

    The mammalian abasic-endonuclease1/redox-factor1 (APE1/Ref1) is an essential protein whose subcellular distribution depends on the cellular physiological status. However, its nuclear localization signals have not been studied in detail. We examined nuclear translocation of APE1, by monitoring enhanced green fluorescent protein (EGFP) fused to APE1. APE1's nuclear localization was significantly decreased by deleting 20 amino acid residues from its N-terminus. Fusion of APE1's N-terminal 20 residues directed nuclear localization of EGFP. An APE1 mutant lacking the seven N-terminal residues (ND7 APE1) showed nearly normal nuclear localization, which was drastically reduced when the deletion was combined with the E12A/D13A double mutation. On the other hand, nearly normal nuclear localization of the full-length E12A/D13A mutant suggests that the first 7 residues and residues 8–13 can independently promote nuclear import. Both far-western analyses and immuno-pull-down assays indicate interaction of APE1 with karyopherin alpha 1 and 2, which requires the 20 N-terminal residues and implicates nuclear importins in APE1's nuclear translocation. Nuclear accumulation of the ND7 APE1(E12A/D13A) mutant after treatment with the nuclear export inhibitor leptomycin B suggests the presence of a previously unidentified nuclear export signal, and the subcellular distribution of APE1 may be regulated by both nuclear import and export. PMID:15942031

  7. Metatarsal torsion in monkeys, apes, humans and australopiths.

    PubMed

    Drapeau, Michelle S M; Harmon, Elizabeth H

    2013-01-01

    This paper presents an analysis of metatarsal torsion in apes, cercopithecoids and humans, compares australopiths with these species, and discusses their inferred foot morphology and function relative to prehensility, arboreality and the presence or absence of a longitudinal arch. Our results show that locomotor modes are reflected in metatarsal torsion values. Apes, which climb vertically with their foot inverted, have hallucal metatarsal heads that are turned toward the other toes and lateral toes that are inverted. Cercopithecoids, which tend to orient their feet in an axis more parallel to the line of motion, present signs of prehensility by having inverted 2nd metatarsals that oppose the hallux, while their two lateral-most metatarsals are strongly everted. Humans, with their rigid feet and longitudinal arches, have all toes that present their plantar surface toward the ground, resulting in hallucal and 2nd metatarsals that are relatively untwisted and the others that are strongly everted. Humans are different from all taxa only for the 2nd and 3rd metatarsal. It is hypothesized that the untwisted 2nd metatarsal reflects the lack of digit opposability of the medial foot and the strongly everted 3rd metatarsal reflects the longitudinal arch. Australopithecus afarensis was characterized by an everted lateral foot, the prerequisite for the development, but not necessarily an indicator, of a longitudinal arch. In Australopithecus africanus, torsion of fragmentary and complete 1st, 2nd, 3rd and 5th metatarsals suggest that the species did not have a foot with monkey- or ape-like prehensile capabilities and did not have a human-like longitudinal arch. In the Swartkrans remains, torsion is consistent with an unprehensile foot. The morphology of the fossils indicates that there was strong selection to orient the plantar surface of the toes facing the ground at the expense of a grasping foot and inversion ability. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Tooth cusp sharpness as a dietary correlate in great apes.

    PubMed

    Berthaume, Michael A

    2014-02-01

    Mammalian molars have undergone heavy scrutiny to determine correlates between morphology and diet. Here, the relationship between one aspect of occlusal morphology, tooth cusp radius of curvature (RoC), and two broad dietary categories, folivory and frugivory, is analyzed in apes. The author hypothesizes that there is a relationship between tooth cusp RoC and diet, and that folivores have sharper teeth than frugivores, and further test the correlation between tooth cusp RoC and tooth cusp size. Eight measures of tooth cusp RoC (two RoCs per cusp) were taken from 53 M(2) s from four species and subspecies of frugivorous apes (Pongo pygmaeus, Pan troglodytes troglodytes, Pan troglodytes schweinfurthii, and Gorilla gorilla gorilla) and two subspecies of folivorous apes (Gorilla beringei beringei, and Gorilla beringei graueri). Phylogenetically corrected ANOVAs were run on the full dataset and several subsets of the full dataset, revealing that, when buccolingual RoCs are taken into account, tooth cusp RoCs can successfully differentiate folivores and frugivores. PCAs revealed that folivores consistently had duller teeth than frugivores. In addition, a weak, statistically significant positive correlation exists between tooth cusp size and tooth cusp RoC. The author hypothesizes differences in tooth cusp RoC are correlated with wear rates, where, per vertical unit of wear, duller cusps will have a longer length of exposed enamel ridge than sharper cusps. More data need to be gathered to determine if the correlation between tooth cusp RoC and tooth cusp size holds true when small primates are considered. Copyright © 2013 Wiley Periodicals, Inc.

  9. The emergence of a new paradigm in ape language research.

    PubMed

    Shanker, Stuart G; King, Barbara J

    2002-10-01

    In recent years we have seen a dramatic shift, in several different areas of communication studies, from an information-theoretic to a dynamic systems paradigm. In an information processing system, communication, whether between cells, mammals, apes, or humans, is said to occur when one organism encodes information into a signal that is transmitted to another organism that decodes the signal. In a dynamic system, all of the elements are continuously interacting with and changing in respect to one another, and an aggregate pattern emerges from this mutual co-action. Whereas the information-processing paradigm looks at communication as a linear, binary sequence of events, the dynamic systems paradigm looks at the relation between behaviors and how the whole configuration changes over time. One of the most dramatic examples of the significance of shifting from an information processing to a dynamic systems paradigm can be found in the debate over the interpretation of recent advances in ape language research (ALR). To some extent, many of the early ALR studies reinforced the stereotype that animal communication is functional and stimulus bound, precisely because they were based on an information-processing paradigm that promoted a static model of communicative development. But Savage-Rumbaugh's recent results with bonobos has introduced an entirely new dimension into this debate. Shifting the terms of the discussion from an information-processing to a dynamic systems paradigm not only highlights the striking differences between Savage-Rumbaugh's research and earlier ALR studies, but further, it sheds illuminating light on the factors that underpin the development of communication skills in great apes and humans, and the relationship between communicative development and the development of language.

  10. Meaning in great ape communication: summarising the debate.

    PubMed

    Scott-Phillips, Thomas C

    2016-01-01

    Does non-human great ape communication have meaning in the same way as human words (and some other human behaviours)? I recently argued that the answer to this question is most likely to be in the negative (Scott-Phillips in Anim Cogn 18(3):801-805, 2015a). Here, I (1) briefly respond to criticism of this view; (2) describe exactly what sort of empirical study could settle the matter; and (3) discuss what the best working hypotheses should be, in the absence of definitive empirical studies.

  11. Ape1/Ref-1 Stimulates GDNF/GFRα1-mediated Downstream Signaling and Neuroblastoma Proliferation

    PubMed Central

    Kang, Mi-Young; Kim, Kweon Young; Yoon, Young; Kang, Yoonsung; Kim, Hong Beum; Youn, Cha Kyung; Kim, Dong-Hui

    2009-01-01

    We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor α1 (GFRα1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRα1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFRα1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFRα1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFRα1-specific RNA experiments demonstrated that the downregulation of GFRα1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLCγ-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFRα signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation. PMID:19915696

  12. Great ape gestures: intentional communication with a rich set of innate signals.

    PubMed

    Byrne, R W; Cartmill, E; Genty, E; Graham, K E; Hobaiter, C; Tanner, J

    2017-09-08

    Great apes give gestures deliberately and voluntarily, in order to influence particular target audiences, whose direction of attention they take into account when choosing which type of gesture to use. These facts make the study of ape gesture directly relevant to understanding the evolutionary precursors of human language; here we present an assessment of ape gesture from that perspective, focusing on the work of the "St Andrews Group" of researchers. Intended meanings of ape gestures are relatively few and simple. As with human words, ape gestures often have several distinct meanings, which are effectively disambiguated by behavioural context. Compared to the signalling of most other animals, great ape gestural repertoires are large. Because of this, and the relatively small number of intended meanings they achieve, ape gestures are redundant, with extensive overlaps in meaning. The great majority of gestures are innate, in the sense that the species' biological inheritance includes the potential to develop each gestural form and use it for a specific range of purposes. Moreover, the phylogenetic origin of many gestures is relatively old, since gestures are extensively shared between different genera in the great ape family. Acquisition of an adult repertoire is a process of first exploring the innate species potential for many gestures and then gradual restriction to a final (active) repertoire that is much smaller. No evidence of syntactic structure has yet been detected.

  13. Great ape gestures: intentional communication with a rich set of innate signals.

    PubMed

    Byrne, R W; Cartmill, E; Genty, E; Graham, K E; Hobaiter, C; Tanner, J

    2017-07-01

    Great apes give gestures deliberately and voluntarily, in order to influence particular target audiences, whose direction of attention they take into account when choosing which type of gesture to use. These facts make the study of ape gesture directly relevant to understanding the evolutionary precursors of human language; here we present an assessment of ape gesture from that perspective, focusing on the work of the "St Andrews Group" of researchers. Intended meanings of ape gestures are relatively few and simple. As with human words, ape gestures often have several distinct meanings, which are effectively disambiguated by behavioural context. Compared to the signalling of most other animals, great ape gestural repertoires are large. Because of this, and the relatively small number of intended meanings they achieve, ape gestures are redundant, with extensive overlaps in meaning. The great majority of gestures are innate, in the sense that the species' biological inheritance includes the potential to develop each gestural form and use it for a specific range of purposes. Moreover, the phylogenetic origin of many gestures is relatively old, since gestures are extensively shared between different genera in the great ape family. Acquisition of an adult repertoire is a process of first exploring the innate species potential for many gestures and then gradual restriction to a final (active) repertoire that is much smaller. No evidence of syntactic structure has yet been detected.

  14. Discrepancies in the occurrence of Balantidium coli between wild and captive African great apes.

    PubMed

    Pomajbíková, Kateřina; Petrželková, Klára J; Profousová, Ilona; Petrášová, Jana; Modrý, David

    2010-12-01

    Balantidium coli is a ciliate reported in many mammalian species, including African great apes. In the former, asymptomatic infections as well as clinical balantidiasis have been reported in captivity. We carried out a cross-sectional study of B. coli in African great apes (chimpanzees, bonobos, and both species of gorillas) and examined 1,161 fecal samples from 28 captive facilities in Europe, plus 2 sanctuaries and 11 wild sites in Africa. Samples were analyzed with the use of Sheather's flotation and merthiolate-iodine-formaldehyde (MIFC) sedimentation. MIFC sedimentation was the more sensitive technique for diagnostics of B. coli in apes. Although not detected in any wild-ape populations, B. coli was diagnosed in 52.6% of captive individuals. Surprisingly, in the apes' feces, trophozoites of B. coli were commonly detected, in contrast with other animals, e.g., Old World monkeys, pigs, etc. Most likely reservoirs for B. coli in captive apes include synantropic rats. High starch diets in captive apes are likely to exacerbate the occurrence of balantidiasis in captive apes.

  15. The Middle Miocene Ape Pierolapithecus catalaunicus Exhibits Extant Great Ape-Like Morphometric Affinities on Its Patella: Inferences on Knee Function and Evolution

    PubMed Central

    Pina, Marta; Almécija, Sergio; Alba, David M.; O'Neill, Matthew C.; Moyà-Solà, Salvador

    2014-01-01

    The mosaic nature of the Miocene ape postcranium hinders the reconstruction of the positional behavior and locomotion of these taxa based on isolated elements only. The fossil great ape Pierolapithecus catalaunicus (IPS 21350 skeleton; 11.9 Ma) exhibits a relatively wide and shallow thorax with moderate hand length and phalangeal curvature, dorsally-oriented metacarpophalangeal joints, and loss of ulnocarpal articulation. This evidence reveals enhanced orthograde postures without modern ape-like below-branch suspensory adaptations. Therefore, it has been proposed that natural selection enhanced vertical climbing (and not suspension per se) in Pierolapithecus catalaunicus. Although limb long bones are not available for this species, its patella (IPS 21350.37) can potentially provide insights into its knee function and thus on the complexity of its total morphological pattern. Here we provide a detailed description and morphometric analyses of IPS 21350.37, which are based on four external dimensions intended to capture the overall patellar shape. Our results reveal that the patella of Pierolapithecus is similar to that of extant great apes: proximodistally short, mediolaterally broad and anteroposteriorly thin. Previous biomechanical studies of the anthropoid knee based on the same measurements proposed that the modern great ape patella reflects a mobile knee joint while the long, narrow and thick patella of platyrrhine and especially cercopithecoid monkeys would increase the quadriceps moment arm in knee extension during walking, galloping, climbing and leaping. The patella of Pierolapithecus differs not only from that of monkeys and hylobatids, but also from that of basal hominoids (e.g., Proconsul and Nacholapithecus), which display slightly thinner patellae than extant great apes (the previously-inferred plesiomorphic hominoid condition). If patellar shape in Pierolapithecus is related to modern great ape-like knee function, our results suggest that increased

  16. A most distant intergeneric hybrid offspring (Larcon) of lesser apes, Nomascus leucogenys and Hylobates lar.

    PubMed

    Hirai, Hirohisa; Hirai, Yuriko; Domae, Hiroshi; Kirihara, Yoko

    2007-12-01

    Unlike humans, which are the sole remaining representatives of a once larger group of bipedal apes (hominins), the "lesser apes" (hylobatids) are a diverse radiation with numerous extant species. Consequently, the lesser apes can provide a valuable evolutionary window onto the possible interactions (e.g., interbreeding) of hominin lineages coexisting in the same time and place. In the present work, we employ chromosomal analyses to verify the hybrid ancestry of an individual (Larcon) produced by two of the most distant genera of lesser apes, Hylobates (lar-group gibbons) and Nomascus (concolor-group gibbons). In addition to a mixed pelage pattern, the hybrid animal carries a 48-chromosome karyotype that consists of the haploid complements of each parental species: Hylobates lar (n = 22) and Nomascus leucogenys leucogenys (n = 26). Studies of this animal's karyotype shed light onto the processes of speciation and genus-level divergence in the lesser apes and, by extension, across the Hominoidea.

  17. The evolution of primate visual self-recognition: evidence of absence in lesser apes

    PubMed Central

    Suddendorf, Thomas; Collier-Baker, Emma

    2009-01-01

    Mirror self-recognition typically emerges in human children in the second year of life and has been documented in great apes. In contrast to monkeys, humans and great apes can use mirrors to inspect unusual marks on their body that cannot be seen directly. Here we show that lesser apes (family Hylobatidae) fail to use the mirror to find surreptitiously placed marks on their head, in spite of being strongly motivated to retrieve directly visible marks from the mirror surface itself and from their own limbs. These findings suggest that the capacity for visual self-recognition evolved in a common ancestor of all great apes after the split from the line that led to modern lesser apes approximately 18 Myr ago. They also highlight the potential of a comparative approach for identifying the neurological and genetic underpinnings of self-recognition and other higher cognitive faculties. PMID:19324830

  18. APES-based procedure for super-resolution SAR imagery with GPU parallel computing

    NASA Astrophysics Data System (ADS)

    Jia, Weiwei; Xu, Xiaojian; Xu, Guangyao

    2015-10-01

    The amplitude and phase estimation (APES) algorithm is widely used in modern spectral analysis. Compared with conventional Fourier transform (FFT), APES results in lower sidelobes and narrower spectral peaks. However, in synthetic aperture radar (SAR) imaging with large scene, without parallel computation, it is difficult to apply APES directly to super-resolution radar image processing due to its great amount of calculation. In this paper, a procedure is proposed to achieve target extraction and parallel computing of APES for super-resolution SAR imaging. Numerical experimental are carried out on Tesla K40C with 745 MHz GPU clock rate and 2880 CUDA cores. Results of SAR image with GPU parallel computing show that the parallel APES is remarkably more efficient than that of CPU-based with the same super-resolution.

  19. Prelinguistic human infants and great apes show different communicative strategies in a triadic request situation.

    PubMed

    Gretscher, Heinz; Tempelmann, Sebastian; Haun, Daniel B M; Liebal, Katja; Kaminski, Juliane

    2017-01-01

    In the present research, we investigate the communicative strategies of 20 month old human infants and great apes when requesting rewards from a human experimenter. Infants and apes both adapted their signals to the attentional state of the experimenter as well as to the location of the reward. Yet, while infants frequently positioned themselves in front of the experimenter and pointed towards a distant reward, apes either remained in the experimenter's line of sight and pointed towards him or moved out of sight and pointed towards the reward. Further, when pointing towards a reward that was placed at a distance from the experimenter, only the infants, and not the apes, took the experimenter's attentional state into account. These results demonstrate that prelinguistic human infants and nonhuman apes use different means when guiding others' attention to a location; indicating that differing cognitive mechanisms may underlie their pointing gestures.

  20. Prelinguistic human infants and great apes show different communicative strategies in a triadic request situation

    PubMed Central

    Gretscher, Heinz; Tempelmann, Sebastian; Haun, Daniel B. M.; Liebal, Katja; Kaminski, Juliane

    2017-01-01

    In the present research, we investigate the communicative strategies of 20 month old human infants and great apes when requesting rewards from a human experimenter. Infants and apes both adapted their signals to the attentional state of the experimenter as well as to the location of the reward. Yet, while infants frequently positioned themselves in front of the experimenter and pointed towards a distant reward, apes either remained in the experimenter’s line of sight and pointed towards him or moved out of sight and pointed towards the reward. Further, when pointing towards a reward that was placed at a distance from the experimenter, only the infants, and not the apes, took the experimenter’s attentional state into account. These results demonstrate that prelinguistic human infants and nonhuman apes use different means when guiding others’ attention to a location; indicating that differing cognitive mechanisms may underlie their pointing gestures. PMID:28384300

  1. The evolution of primate visual self-recognition: evidence of absence in lesser apes.

    PubMed

    Suddendorf, Thomas; Collier-Baker, Emma

    2009-05-07

    Mirror self-recognition typically emerges in human children in the second year of life and has been documented in great apes. In contrast to monkeys, humans and great apes can use mirrors to inspect unusual marks on their body that cannot be seen directly. Here we show that lesser apes (family Hylobatidae) fail to use the mirror to find surreptitiously placed marks on their head, in spite of being strongly motivated to retrieve directly visible marks from the mirror surface itself and from their own limbs. These findings suggest that the capacity for visual self-recognition evolved in a common ancestor of all great apes after the split from the line that led to modern lesser apes approximately 18 Myr ago. They also highlight the potential of a comparative approach for identifying the neurological and genetic underpinnings of self-recognition and other higher cognitive faculties.

  2. Elevated level of acetylation of APE1 in tumor cells modulates DNA damage repair

    PubMed Central

    Sengupta, Shiladitya; Mantha, Anil K.; Song, Heyu; Roychoudhury, Shrabasti; Nath, Somsubhra; Ray, Sutapa; Bhakat, Kishor K.

    2016-01-01

    Apurinic/apyrimidinic (AP) sites are frequently generated in the genome by spontaneous depurination/depyrimidination or after removal of oxidized/modified bases by DNA glycosylases during the base excision repair (BER) pathway. Unrepaired AP sites are mutagenic and block DNA replication and transcription. The primary enzyme to repair AP sites in mammalian cells is AP endonuclease (APE1), which plays a key role in this repair pathway. Although overexpression of APE1 in diverse cancer types and its association with chemotherapeutic resistance are well documented, alteration of posttranslational modification of APE1 and modulation of its functions during tumorigenesis are largely unknown. Here, we show that both classical histone deacetylase HDAC1 and NAD+-dependent deacetylase SIRT1 regulate acetylation level of APE1 and acetylation of APE1 enhances its AP-endonuclease activity both in vitro and in cells. Modulation of APE1 acetylation level in cells alters AP site repair capacity of the cell extracts in vitro. Primary tumor tissues of diverse cancer types have higher level of acetylated APE1 (AcAPE1) compared to adjacent non-tumor tissue and exhibit enhanced AP site repair capacity. Importantly, in the absence of APE1 acetylation, cells accumulate AP sites in the genome and show increased sensitivity to DNA damaging agents. Together, our study demonstrates that elevation of acetylation level of APE1 in tumor could be a novel mechanism by which cells handle the elevated levels of DNA damages in response to genotoxic stress and maintain sustained proliferation. PMID:27655688

  3. Human apurinic/apyrimidinic endonuclease 1 (APE1) has 3' RNA phosphatase and 3' exoribonuclease activities.

    PubMed

    Chohan, Manbir; Mackedenski, Sebastian; Li, Wai-Ming; Lee, Chow H

    2015-01-30

    Apurinic/apyrimidinic endonuclease 1 (APE1) is the predominant mammalian enzyme in DNA base excision repair pathway that cleaves the DNA backbone immediately 5' to abasic sites. In addition to its abasic endonuclease activity, APE1 has 3' phosphatase and 3'-5' exonuclease activities against DNA. We recently identified APE1 as an endoribonuclease that preferentially cleaves at UA, UG, and CA sites in single-stranded regions of RNAs and can regulate c-myc mRNA level and half-life in cells. APE1 can also endonucleolytically cleave abasic single-stranded RNA. Here, we show for the first time that the human APE1 has 3' RNA phosphatase and 3' exoribonuclease activities. Using three distinct RNA substrates, we show that APE1, but not RNase A, can remove the phosphoryl group from the 3' end of RNA decay products. Studies using various site-directed APE1 mutant proteins (H309N, H309S, D283N, N68A, D210N, Y171F, D308A, F266A, and D70A) suggest that the 3' RNA phosphatase activity shares the same active center as its other known nuclease activities. A number of APE1 variants previously identified in the human population, including the most common D148E variant, have greater than 80% reduction in the 3' RNA phosphatase activity. APE1 can remove a ribonucleotide from the 3' overhang of RNA decay product, but its 3'-5' exoribonuclease activity against unstructured poly(A), poly(C), and poly(U) RNAs is relatively weak. This study further underscores the significance of understanding the role of APE1 in RNA metabolism in vivo.

  4. Unique human orbital morphology compared with that of apes

    PubMed Central

    Denion, Eric; Hitier, Martin; Guyader, Vincent; Dugué, Audrey-Emmanuelle; Mouriaux, Frédéric

    2015-01-01

    Humans’ and apes’ convergent (front-facing) orbits allow a large overlap of monocular visual fields but are considered to limit the lateral visual field extent. However, humans can greatly expand their lateral visual fields using eye motion. This study aimed to assess whether the human orbital morphology was unique compared with that of apes in avoiding lateral visual field obstruction. The orbits of 100 human skulls and 120 ape skulls (30 gibbons; 30 orangutans; 30 gorillas; 30 chimpanzees and bonobos) were analyzed. The orbital width/height ratio was calculated. Two orbital angles representing orbital convergence and rearward position of the orbital margin respectively were recorded using a protractor and laser levels. Humans have the largest orbital width/height ratio (1.19; p < 0.001). Humans and gibbons have orbits which are significantly less convergent than those of chimpanzees / bonobos, gorillas and orangutans (p < 0.001). These elements suggest a morphology favoring lateral vision in humans. More specifically, the human orbit has a uniquely rearward temporal orbital margin (107.1°; p < 0.001), suitable for avoiding visual obstruction and promoting lateral visual field expansion through eye motion. Such an orbital morphology may have evolved mainly as an adaptation to open-country habitat and bipedal locomotion. PMID:26111067

  5. Comparative mapping of human alphoid centromeric sequences in great apes

    SciTech Connect

    Archidiacono, N.; Antonacci, R.; Marzella, R.

    1994-09-01

    Metaphase spreads from chimpanzees (Pan troglodytes and Pan paniscus) and gorilla (Gorilla gorilla) have been hybridized in situ with 27 alphoid DNA probes specific for the centromere of human chromosomes, to investigate the evolutionary relationship between centromeric regions of human and great apes. The results showed that most human probes do not recognize their corresponding homologs in great apes. Chromosome X is the only chromosome showing localization consistency in all the four species. Each suprachromosomal family (SCF) exhibits a distinct and peculiar evolutionary history. SCF1 (chromosomes 1, 3, 6, 7, 19, 12, 16) is very heterogeneous: some probes gave intense signals, but always on non-homologous chromosomes; others did not produce any hybridization signal. All probes localized on SCF2 (chromosomes 2, 4, 8, 9, 13, 14, 15, 18, 20, 21, and 22) recognize a single chromosome: chromosome 11 (phylogenetic IX) in PTR and PPA; chromosome 4 (phylogenetic V) in GGO. SCF3 subsets (chromosomes 1, 11, 17, X) are substantially conserved in PTR and PPA, but not in GGO, with the exception restricted to chromosome X. No signals have been detected on PPA chromosomes I, III, IV, V, VI and in PTR chromosomes V, suggesting that the centromeric region of some chromsomes have probably lost homology with human alphoid sequences.

  6. The strength of great apes and the speed of humans.

    PubMed

    Walker, Alan

    2009-04-01

    Cliff Jolly developed a causal model of human origins in his paper "The Seed-Eaters," published in 1970. He was one of the first to attempt this, and the paper has since become a classic. I do not have such grand goals; instead, I seek to understand a major difference between the living great apes and humans. More than 50 years ago, Maynard Smith and Savage (1956) showed that the musculoskeletal systems of mammals can be adapted for strength at one extreme and speed at the other but not both. Great apes are adapted for strength--chimpanzees have been shown to be about four times as strong as fit young humans when normalized for body size. The corresponding speed that human limb systems gain at the expense of power is critical for effective human activities such as running, throwing, and manipulation, including tool making. The fossil record can shed light on when the change from power to speed occurred. I outline a hypothesis that suggests that the difference in muscular performance between the two species is caused by chimpanzees having many fewer small motor units than humans, which leads them, in turn, to contract more muscle fibers earlier in any particular task. I outline a histological test of this hypothesis.

  7. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    PubMed Central

    Kim, Hyun-Suk; Guo, Chunlu; Thompson, Eric L.; Jiang, Yanlin; Kelley, Mark R.; Vasko, Michael R.; Lee, Suk-Hee

    2015-01-01

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 hours. In cultures where APE1 expression was reduced by ~80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Reduction in APE1 expression also altered the expression of the NER proteins RPA70 and XPA in sensory neuronal cultures. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226+177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons. PMID:26164266

  8. Lucanthone and its derivative hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding

    SciTech Connect

    Naidu, M.; Naidu, M.; Agarwal, R.; Pena, L.A.; Cunha, L.; Mezei, M.; Shen, M.; Wilson, D.M.; Liu, Y.; Sanchez, Z.; Chaudhary, P.; Wilson, S.H.; Waring, M.J.

    2011-09-15

    Lucanthone and hycanthone are thioxanthenone DNA intercalators used in the 1980s as antitumor agents. Lucanthone is in Phase I clinical trial, whereas hycanthone was pulled out of Phase II trials. Their potential mechanism of action includes DNA intercalation, inhibition of nucleic acid biosyntheses, and inhibition of enzymes like topoisomerases and the dual function base excision repair enzyme apurinic endonuclease 1 (APE1). Lucanthone inhibits the endonuclease activity of APE1, without affecting its redox activity. Our goal was to decipher the precise mechanism of APE1 inhibition as a prerequisite towards development of improved therapeutics that can counteract higher APE1 activity often seen in tumors. The IC{sub 50} values for inhibition of APE1 incision of depurinated plasmid DNA by lucanthone and hycanthone were 5 {mu}M and 80 nM, respectively. The K{sub D} values (affinity constants) for APE1, as determined by BIACORE binding studies, were 89 nM for lucanthone/10 nM for hycanthone. APE1 structures reveal a hydrophobic pocket where hydrophobic small molecules like thioxanthenones can bind, and our modeling studies confirmed such docking. Circular dichroism spectra uncovered change in the helical structure of APE1 in the presence of lucanthone/hycanthone, and notably, this effect was decreased (Phe266Ala or Phe266Cys or Trp280Leu) or abolished (Phe266Ala/Trp280Ala) when hydrophobic site mutants were employed. Reduced inhibition by lucanthone of the diminished endonuclease activity of hydrophobic mutant proteins (as compared to wild type APE1) supports that binding of lucanthone to the hydrophobic pocket dictates APE1 inhibition. The DNA binding capacity of APE1 was marginally inhibited by lucanthone, and not at all by hycanthone, supporting our hypothesis that thioxanthenones inhibit APE1, predominantly, by direct interaction. Finally, lucanthone-induced degradation was drastically reduced in the presence of short and long lived free radical scavengers, e

  9. APE/Ref-1 makes fine-tuning of CD40-induced B cell proliferation

    PubMed Central

    Merluzzi, Sonia; Gri, Giorgia; Gattei, Valter; Pagano, Michele; Pucillo, Carlo

    2009-01-01

    Apurinic/apyrimidinic endonuclease-1/Redox factor-1, a multifunctional DNA base excision repair and redox regulation enzyme, plays an important role in oxidative signalling, transcription factor regulation, and cell cycle control. Recently, we have demonstrated that following the triggering of CD40 on B cells, APE/Ref-1 translocates from the cytoplasm to the nucleus and regulates the activity of B cell-specific transcription factors. In the present paper we investigate whether APE/Ref-1 plays a role in controlling CD40-mediated B cell proliferation too. We demonstrate a concurrent increase in proliferation and decrease in apoptosis of primary mouse B cells activated by CD40 cross-linking and transfected with functional APE/Ref-1 antisense oligonucleotide. Moreover, we provide evidence that a redox-mediated signalling mechanism is involved in this process and we propose that APE/Ref-1, controlling the intracellular redox state, may also affect the cell cycle by inducing nucleus-cytoplasm redistribution of p21. Together, these findings suggest that APE/Ref-1 could act as a negative regulator in an adaptive response to elevated ROS levels following CD40 cross-linking. Considering the important role of ROS and APE/Ref-1 in CD40-mediated B cell proliferation, our data will contribute to understand the mechanisms of tumor escape and suggest APE/Ref-1 as a novel target for tumor therapeutic approaches. PMID:18617267

  10. APE/Ref-1 makes fine-tuning of CD40-induced B cell proliferation.

    PubMed

    Merluzzi, Sonia; Gri, Giorgia; Gattei, Valter; Pagano, Michele; Pucillo, Carlo

    2008-08-01

    Apurinic/apyrimidinic endonuclease-1/Redox factor-1, a multifunctional DNA base excision repair and redox regulation enzyme, plays an important role in oxidative signalling, transcription factor regulation, and cell cycle control. Recently, we have demonstrated that following the triggering of CD40 on B cells, APE/Ref-1 translocates from the cytoplasm to the nucleus and regulates the activity of B cell-specific transcription factors. In the present paper we investigate whether APE/Ref-1 plays a role in controlling CD40-mediated B cell proliferation too. We demonstrate a concurrent increase in proliferation and decrease in apoptosis of primary mouse B cells activated by CD40 cross-linking and transfected with functional APE/Ref-1 antisense oligonucleotide. Moreover, we provide evidence that a redox-mediated signalling mechanism is involved in this process and we propose that APE/Ref-1, controlling the intracellular redox state, may also affect the cell cycle by inducing nucleus-cytoplasm redistribution of p21. Together, these findings suggest that APE/Ref-1 could act as a negative regulator in an adaptive response to elevated ROS levels following CD40 cross-linking. Considering the important role of ROS and APE/Ref-1 in CD40-mediated B cell proliferation, our data will contribute to understand the mechanisms of tumor escape and suggest APE/Ref-1 as a novel target for tumor therapeutic approaches.

  11. Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells

    PubMed Central

    Chen, Tian; Liu, Zhi; Sun, Wenhua; Li, Jingyu; Liang, Yan; Yang, Xianrui; Xu, Yang; Yu, Mei; Tian, Weidong; Chen, Guoqing; Bai, Ding

    2015-01-01

    Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway. PMID:26639148

  12. ape 3.0: New tools for distance-based phylogenetics and evolutionary analysis in R.

    PubMed

    Popescu, Andrei-Alin; Huber, Katharina T; Paradis, Emmanuel

    2012-06-01

    Reflecting its continuously increasing versatility and functionality, the popularity of the ape (analysis of phylogenetics and evolution) software package has grown steadily over the years. Among its features, it has a strong distance-based component allowing the user to compute distances from aligned DNA sequences based on most methods from the literature and also build phylogenetic trees from them. However, even data generated with modern genomic approaches can fail to give rise to sufficiently reliable distance estimates. One way to overcome this problem is to exclude such estimates from data analysis giving rise to an incomplete distance data set (as opposed to a complete one). So far their analysis has been out of reach for ape. To remedy this, we have incorporated into ape several methods from the literature for phylogenetic inference from incomplete distance matrices. In addition, we have also extended ape's repertoire for phylogenetic inference from complete distances, added a new object class to efficiently encode sets of splits of taxa, and extended the functionality of some of its existing functions. ape is distributed through the Comprehensive R Archive Network: http://cran.r-project.org/web/packages/ape/index.html Further information may be found at http://ape.mpl.ird.fr/pegas/

  13. Assessing endocranial variations in great apes and humans using 3D data from virtual endocasts.

    PubMed

    Bienvenu, Thibaut; Guy, Franck; Coudyzer, Walter; Gilissen, Emmanuel; Roualdès, Georges; Vignaud, Patrick; Brunet, Michel

    2011-06-01

    Modern humans are characterized by their large, complex, and specialized brain. Human brain evolution can be addressed through direct evidence provided by fossil hominid endocasts (i.e. paleoneurology), or through indirect evidence of extant species comparative neurology. Here we use the second approach, providing an extant comparative framework for hominid paleoneurological studies. We explore endocranial size and shape differences among great apes and humans, as well as between sexes. We virtually extracted 72 endocasts, sampling all extant great ape species and modern humans, and digitized 37 landmarks on each for 3D generalized Procrustes analysis. All species can be differentiated by their endocranial shape. Among great apes, endocranial shapes vary from short (orangutans) to long (gorillas), perhaps in relation to different facial orientations. Endocranial shape differences among African apes are partly allometric. Major endocranial traits distinguishing humans from great apes are endocranial globularity, reflecting neurological reorganization, and features linked to structural responses to posture and bipedal locomotion. Human endocasts are also characterized by posterior location of foramina rotunda relative to optic canals, which could be correlated to lesser subnasal prognathism compared to living great apes. Species with larger brains (gorillas and humans) display greater sexual dimorphism in endocranial size, while sexual dimorphism in endocranial shape is restricted to gorillas, differences between males and females being at least partly due to allometry. Our study of endocranial variations in extant great apes and humans provides a new comparative dataset for studies of fossil hominid endocasts. Copyright © 2011 Wiley-Liss, Inc.

  14. The limits of endowment effects in great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus).

    PubMed

    Kanngiesser, Patricia; Santos, Laurie R; Hood, Bruce M; Call, Josep

    2011-11-01

    The endowment effect describes the bias that people often value things that they possess more than things they do not possess. Thus, they are often reluctant to trade items in their possession for items of equivalent value. Some nonhuman primates appear to share this bias with humans, but it remains an open question whether they show endowment effects to the same extent as humans do. We investigated endowment effects in all four great ape species (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus) by varying whether apes were endowed with food items (Experiment 1, N = 22) or tools that were instrumental in retrieving food (Experiment 2, N = 23). We first assessed apes' preferences for items of a pair and their willingness to trade items in their possession. We then endowed apes with one item of a pair and offered them to trade for the other item. Apes showed endowment effects for food, but not for tools. In Experiment 3, we endowed bonobos (N = 4) and orangutans (N = 5) with either one or 12 food items. Endowment effects did not differ between species and were not influenced by the number of endowed food items. Our findings suggest that endowment effects in great apes are restricted to immediate food gratification and remain unaffected by the quantity of food rewards. However, endowment effects do not seem to extend to other, nonconsumable possessions even when they are instrumental in retrieving food. In general, apes do not show endowment effects across a range of different commodities as humans typically do.

  15. APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress

    PubMed Central

    Willis, Jeremy; Patel, Yogin; Lentz, Barry L.; Yan, Shan

    2013-01-01

    The base excision repair pathway is largely responsible for the repair of oxidative stress-induced DNA damage. However, it remains unclear how the DNA damage checkpoint is activated by oxidative stress at the molecular level. Here, we provide evidence showing that hydrogen peroxide (H2O2) triggers checkpoint kinase 1 (Chk1) phosphorylation in an ATR [ataxia-telangiectasia mutated (ATM) and Rad3-related]-dependent but ATM-independent manner in Xenopus egg extracts. A base excision repair protein, Apurinic/apyrimidinic (AP) endonuclease 2 (APE2, APN2, or APEX2), is required for the generation of replication protein A (RPA)-bound single-stranded DNA, the recruitment of a checkpoint protein complex [ATR, ATR-interacting protein (ATRIP), and Rad9] to damage sites, and H2O2-induced Chk1 phosphorylation. A conserved proliferating cell nuclear antigen interaction protein box of APE2 is important for the recruitment of APE2 to H2O2-damaged chromatin. APE2 3′-phosphodiesterase and 3′-5′ exonuclease activity is essential for single-stranded DNA generation in the 3′–5′ direction from single-stranded breaks, referred to as single-stranded break end resection. In addition, APE2 associates with Chk1, and a serine residue (S86) in the Chk1-binding motif of APE2 is essential for Chk1 phosphorylation, indicating a Claspin-like but distinct role for APE2 in ATR-Chk1 signaling. Our data indicate that APE2 plays a vital and previously unexpected role in ATR-Chk1 checkpoint signaling in response to oxidative stress. Thus, our findings shed light on a distinct mechanism of how an ATR-Chk1–dependent DNA damage checkpoint is mediated by APE2 in the oxidative stress response. PMID:23754435

  16. Do apes know that they could be wrong?

    PubMed

    Call, Josep

    2010-09-01

    When confronted with uncertain or incomplete information in decision-making situations, monkeys and apes opt for either escaping the situation or seeking additional information. These responses have been interpreted as evidence of metacognitive abilities. However, this interpretation has been challenged. On the one hand, studies using the information-seeking paradigm have been criticized because subjects may simply engage in a search for information routine (e.g., search until spot the reward) without any metacognitive involvement. On the other hand, studies using the escape response paradigm have been criticized because subjects may not recognize their own state of uncertainty but have learned to use the escape response in the presence of certain stimuli configurations that create uncertainty. The current study attempted to address these two criticisms by presenting great apes (seven gorillas, eight chimpanzees, four bonobos, seven orangutans) with a seeking information task whose basic procedure consisted of presenting two hollow tubes, baiting one of them and letting subjects choose. Conditions varied depending on whether subjects had visual access to the baiting, the cost associated with seeking information, the time interval between baiting and choosing, the food quality and the additional information offered regarding the food's location. Although subjects showed a high retrieval accuracy when they had witnessed the baiting, they were more likely to check inside the tube before choosing when high stakes were involved (Experiment 3) or after a longer period of time had elapsed between the baiting and the retrieval of the reward (Experiment 2). In contrast, providing subjects with indirect auditory information about the food's location or increasing the cost of checking reduced checking before choosing (Experiment 1). Taken together, these findings suggest that subjects knew that they could be wrong when choosing.

  17. Remnants of an ancient forest provide ecological context for Early Miocene fossil apes.

    PubMed

    Michel, Lauren A; Peppe, Daniel J; Lutz, James A; Driese, Steven G; Dunsworth, Holly M; Harcourt-Smith, William E H; Horner, William H; Lehmann, Thomas; Nightingale, Sheila; McNulty, Kieran P

    2014-01-01

    The lineage of apes and humans (Hominoidea) evolved and radiated across Afro-Arabia in the early Neogene during a time of global climatic changes and ongoing tectonic processes that formed the East African Rift. These changes probably created highly variable environments and introduced selective pressures influencing the diversification of early apes. However, interpreting the connection between environmental dynamics and adaptive evolution is hampered by difficulties in locating taxa within specific ecological contexts: time-averaged or reworked deposits may not faithfully represent individual palaeohabitats. Here we present multiproxy evidence from Early Miocene deposits on Rusinga Island, Kenya, which directly ties the early ape Proconsul to a widespread, dense, multistoried, closed-canopy tropical seasonal forest set in a warm and relatively wet, local climate. These results underscore the importance of forested environments in the evolution of early apes.

  18. Miocene small-bodied ape from Eurasia sheds light on hominoid evolution.

    PubMed

    Alba, David M; Almécija, Sergio; DeMiguel, Daniel; Fortuny, Josep; Pérez de los Ríos, Miriam; Pina, Marta; Robles, Josep M; Moyà-Solà, Salvador

    2015-10-30

    Miocene small-bodied anthropoid primates from Africa and Eurasia are generally considered to precede the divergence between the two groups of extant catarrhines—hominoids (apes and humans) and Old World monkeys—and are thus viewed as more primitive than the stem ape Proconsul. Here we describe Pliobates cataloniae gen. et sp. nov., a small-bodied (4 to 5 kilograms) primate from the Iberian Miocene (11.6 million years ago) that displays a mosaic of primitive characteristics coupled with multiple cranial and postcranial shared derived features of extant hominoids. Our cladistic analyses show that Pliobates is a stem hominoid that is more derived than previously described small catarrhines and Proconsul. This forces us to reevaluate the role played by small-bodied catarrhines in ape evolution and provides key insight into the last common ancestor of hylobatids (gibbons) and hominids (great apes and humans).

  19. Down-regulation of apurinic/apyrimidinic endonuclease 1 (APE1) in spinal motor neurones under oxidative stress.

    PubMed

    Chu, Tak-Ho; Guo, Anchen; Wu, Wutian

    2014-06-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is an intermediate enzyme in base excision repair which is important for removing damaged nucleotides under normal and pathological conditions. Accumulation of damaged bases causes genome instability and jeopardizes cell survival. Our study is to examine APE1 regulation under oxidative stress in spinal motor neurones which are vulnerable to oxidative insult. We challenged the motor neurone-like cell line NSC-34 with hydrogen peroxide and delineated APE1 function by applying various inhibitors. We also examined the expression of APE1 in spinal motor neurones after spinal root avulsion in adult rats. We showed that hydrogen peroxide induced APE1 down-regulation and cell death in a differentiated motor neurone-like cell line. Inhibiting the two functional domains of APE1, namely, DNA repair and redox domains potentiated hydrogen peroxide induced cell death. We further showed that p53 phosphorylation early after hydrogen peroxide treatment might contribute to the down-regulation of APE1. Our in vivo results similarly showed that APE1 was down-regulated after root avulsion injury in spinal motor neurones. Delay of motor neurone death suggested that APE1 might not cause immediate cell death but render motor neurones vulnerable to further oxidative insults. We conclude that spinal motor neurones down-regulate APE1 upon oxidative stress. This property renders motor neurones susceptible to continuous challenge of oxidative stress in pathological conditions. © 2013 British Neuropathological Society.

  20. [The expression of APE1 and its correlation with prognostic significance after 252Cf radiotherapy in cervical cancer].

    PubMed

    Qing, Yi; Wang, Dong; Lei, Xin; Xiang, De-Bing; Li, Meng-Xia; Li, Zeng-Peng; Shan, Jin-Lu

    2009-01-01

    To investigate the expression feature of the apurinic/apyrimidinic endonuclease (APE1) and its correlation with clinicopathology and prognostic significance after 252Cf radiotherapy in cervical cancer. The expression of APE1 was detected by immunohistochemistry technique in 89 cases of cervical cancer (treated by 252Cf), 15 cases cervical intraepithelial neoplasia (CIN) and 10 cases of normal cervical tissue, and its association with clinicopathological data as well as prognosis were analyzed. The expression of APE1 in cervical cancer is higher significantly than that in normal cervical tissue and CIN (P < 0.01). In normal cervical tissue and CIN, the APE1 express was located in the nucleus. In cervical cancer, the APE1 express was located in the nucleus (59), cytoplasm (8) or nucleus and cytoplasm (22), the location of APE1 was related with FIGO stage and pathological grade (P < 0.01), and not related with lymph node metastasis. The level of APE1 express related with FIGO stage, pathological grade and lymph node metastasis (P < 0.05), and not related with age and pathological type. The Kaplan-Meier survival analysis demonstrated that the survival time of the group of APE1 nucleus expression (median survival time is 70.9 months) and the group of APE1 low expression (median survival time is 75.8 months) is longer significantly than that of the group of APE1 cytoplasm expression (median survival time is 57.8 months) and the group of APE1 high expression (median survival time is 56.5 months) (P = 0.025, 0.001). The dystopic express of APE1 might play a pivotal role in carcinogenesis and progression of cervical cancer, and the express of APE1 might estimate the prognosis after 252Cf radiotherapy.

  1. Intuitions about Gravity and Solidity in Great Apes: The Tubes Task

    ERIC Educational Resources Information Center

    Cacchione, Trix; Call, Josep

    2010-01-01

    We investigated whether great apes, like human infants, monkeys and dogs, are subject to a strong gravity bias when tested with the tubes task, and--in case of mastery--what the source of competence on the tubes task is. We presented 22 apes with three versions of the tubes task, in which an object is dropped down a tube connected to one of three…

  2. APE2 Zf-GRF facilitates 3'-5' resection of DNA damage following oxidative stress

    SciTech Connect

    Wallace, Bret D.; Berman, Zachary; Mueller, Geoffrey A.; Lin, Yunfeng; Chang, Timothy; Andres, Sara N.; Wojtaszek, Jessica L.; DeRose, Eugene F.; Appel, C. Denise; London, Robert E.; Yan, Shan; Williams, R. Scott

    2016-12-27

    The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3'-5' nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high homology with DDR proteins Topoisomerase 3α (TOP3α) and NEIL3 (Nei-like DNA glycosylase 3), as well as transcription and RNA regulatory proteins, such as TTF2 (transcription termination factor 2), TFIIS, and RPB9. Biochemical and NMR results establish the nucleic acid-binding activity of the Zf-GRF domain. Moreover, an APE2 Zf-GRF X-ray structure and small-angle X-ray scattering analyses show that the Zf-GRF fold is typified by a crescent-shaped ssDNA binding claw that is flexibly appended to an APE2 endonuclease/exonuclease/phosphatase (EEP) catalytic core. Structure-guided Zf-GRF mutations impact APE2 DNA binding and 3'-5' exonuclease processing, and also prevent efficient APE2-dependent RPA recruitment to damaged chromatin and activation of the ATR-Chk1 DDR pathway in response to oxidative stress in Xenopus egg extracts. Collectively, our data unveil the APE2 Zf-GRF domain as a nucleic acid interaction module in the regulation of a key single-strand break resection function of APE2, and also reveal topologic similarity of the Zf-GRF to the zinc ribbon domains of TFIIS and RPB9.

  3. Intuitions about Gravity and Solidity in Great Apes: The Tubes Task

    ERIC Educational Resources Information Center

    Cacchione, Trix; Call, Josep

    2010-01-01

    We investigated whether great apes, like human infants, monkeys and dogs, are subject to a strong gravity bias when tested with the tubes task, and--in case of mastery--what the source of competence on the tubes task is. We presented 22 apes with three versions of the tubes task, in which an object is dropped down a tube connected to one of three…

  4. Spatial and Temporal Dynamics of a Mortality Event among Central African Great Apes.

    PubMed

    Cameron, Kenneth N; Reed, Patricia; Morgan, David B; Ondzié, Alain I; Sanz, Crickette M; Kühl, Hjalmar S; Olson, Sarah H; Leroy, Eric; Karesh, William B; Mundry, Roger

    2016-01-01

    In 2006-2007 we observed an unusual mortality event among apes in northern Republic of Congo that, although not diagnostically confirmed, we believe to have been a disease outbreak. In 2007-2011 we conducted ape nest surveys in the region, recording 11,835 G. g. gorilla nests (2,262 groups) and 5,548 P. t. troglodytes nests (2,139 groups). We developed a statistical model to determine likely points of origin of the outbreak to help identify variables associated with disease emergence and spread. We modeled disease spread across the study area, using suitable habitat conditions for apes as proxy for local ape densities. Infectious status outputs from that spread model were then used alongside vegetation, temperature, precipitation and human impact factors as explanatory variables in a Generalized Linear Model framework to explain observed 2007-2011 ape nest trends in the region. The best models predicted emergence in the western region of Odzala-Kokoua National Park and north of the last confirmed Ebola virus disease epizootics. Roads were consistently associated with attenuation of modeled virus spread. As disease is amongst the leading threats to great apes, gaining a better understanding of disease transmission dynamics in these species is imperative. Identifying ecological drivers underpinning a disease emergence event and transmission dynamics in apes is critical to creating better predictive models to guide wildlife management, develop potential protective measures for wildlife and to reduce potential zoonotic transmission to humans. The results of our model represent an important step in understanding variables related to great ape disease ecology in Central Africa.

  5. Impact of APE1/Ref-1 Redox Inhibition on Pancreatic Tumor Growth

    PubMed Central

    Fishel, Melissa L.; Jiang, Yanlin; Rajeshkumar, N. V.; Scandura, Glenda; Sinn, Anthony L.; He, Ying; Shen, Changyu; Jones, David R.; Pollok, Karen E.; Ivan, Mircea; Maitra, Anirban; Kelley, Mark R.

    2011-01-01

    Pancreatic cancer is an especially deadly form of cancer with a survival rate <2%. Pancreatic cancers respond poorly to existing chemotherapeutic agents and radiation, and progress for the treatment of pancreatic cancer remains elusive. To address this unmet medical need, a better understanding of critical pathways and molecular mechanisms involved in pancreatic tumor development, progression and resistance to traditional therapy is therefore critical. Reduction-oxidation (redox) signaling systems are emerging as important targets in pancreatic cancer. AP endonuclease1/ Redox effector factor 1 (APE1/Ref-1) is upregulated in human pancreatic cancer cells and modulation of its redox activity blocks the proliferation and migration of pancreatic cancer cells as well as pancreatic cancer-associated endothelial cells (PCECs) in vitro. Modulation of APE1/Ref-1 using a specific inhibitor of APE1/Ref-1’s redox function, E3330 leads to a decrease in transcription factor activity for NFκB, AP-1, and HIF1 in vitro. This study aims to further establish the redox signaling protein APE1/Ref-1 as a molecular target in pancreatic cancer. Here, we show that inhibition of APE1/Ref-1 via E3330 results in tumor growth inhibition in cell lines as well as pancreatic cancer xenograft models in mice. Pharmacokinetic (PK) studies also demonstrate that E3330 attains >10 μM blood concentrations and is detectable in tumor xenografts. Through inhibition of APE1/Ref-1, the activity of NFκB, AP-1, and HIF1α which are key transcriptional regulators involved in survival, invasion and metastasis is blocked. These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted. PMID:21700832

  6. Spatial and Temporal Dynamics of a Mortality Event among Central African Great Apes

    PubMed Central

    Cameron, Kenneth N.; Reed, Patricia; Morgan, David B.; Ondzié, Alain I.; Sanz, Crickette M.; Kühl, Hjalmar S.; Olson, Sarah H.; Leroy, Eric; Karesh, William B.; Mundry, Roger

    2016-01-01

    In 2006–2007 we observed an unusual mortality event among apes in northern Republic of Congo that, although not diagnostically confirmed, we believe to have been a disease outbreak. In 2007–2011 we conducted ape nest surveys in the region, recording 11,835 G. g. gorilla nests (2,262 groups) and 5,548 P. t. troglodytes nests (2,139 groups). We developed a statistical model to determine likely points of origin of the outbreak to help identify variables associated with disease emergence and spread. We modeled disease spread across the study area, using suitable habitat conditions for apes as proxy for local ape densities. Infectious status outputs from that spread model were then used alongside vegetation, temperature, precipitation and human impact factors as explanatory variables in a Generalized Linear Model framework to explain observed 2007–2011 ape nest trends in the region. The best models predicted emergence in the western region of Odzala-Kokoua National Park and north of the last confirmed Ebola virus disease epizootics. Roads were consistently associated with attenuation of modeled virus spread. As disease is amongst the leading threats to great apes, gaining a better understanding of disease transmission dynamics in these species is imperative. Identifying ecological drivers underpinning a disease emergence event and transmission dynamics in apes is critical to creating better predictive models to guide wildlife management, develop potential protective measures for wildlife and to reduce potential zoonotic transmission to humans. The results of our model represent an important step in understanding variables related to great ape disease ecology in Central Africa. PMID:27192424

  7. Behavioral cues that great apes use to forage for hidden food.

    PubMed

    Buttelmann, David; Call, Josep; Tomasello, Michael

    2008-01-01

    We conducted three studies to examine whether the four great ape species (chimpanzees, bonobos, gorillas, and orangutans) are able to use behavioral experimenter-given cues in an object-choice task. In the subsequent experimental conditions subjects were presented with two eggs, one of which contained food and the other did not. In Study 1 the experimenter examined both eggs by smelling or shaking them, but only made a failed attempt to open (via biting) the egg containing food. In a control condition, the experimenter examined and attempted to open both eggs, but in reverse order to control for stimulus enhancement. The apes significantly preferred the egg that was first examined and then bitten, but had no preference in a baseline condition in which there were no cues. In Study 2, we investigated whether the apes could extend this ability to cues not observed in apes so far (i.e., attempting to pull apart the egg), as well as whether they made this discrimination based on the function of the action the experimenter performed. Subjects significantly preferred eggs presented with this novel cue, but did not prefer eggs presented with a novel but functionally irrelevant action. In Study 3, apes did not interpret human actions as cues to food-location when they already knew that the eggs were empty. Thus, great apes were able to use a variety of experimenter-given cues associated with foraging actions to locate hidden food and thereby were partially sensitive to the general purpose underlying these actions.

  8. The multifunctional DNA repair/redox enzyme Ape1/Ref-1 promotes survival of neurons after oxidative stress.

    PubMed

    Vasko, Michael R; Guo, Chunlu; Kelley, Mark R

    2005-03-02

    Although correlative studies demonstrate a reduction in the expression of apurinic/apyrimidinic endonuclease/redox effector factor (Ape1/Ref-1 or Ape1) in neural tissues after neuronal insult, the role of Ape1 in regulating neurotoxicity remains to be elucidated. To address this issue, we examined the effects of reducing Ape1 expression in primary cultures of hippocampal and sensory neurons on several endpoints of neurotoxicity induced by H2O2. Ape1 is highly expressed in hippocampal and sensory neurons grown in culture as indicated by immunohistochemistry, immunoblotting and activity. Exposing hippocampal or sensory neuronal cultures to 25 or 50 nM small interfering RNA to Ape1 (Ape1siRNA), respectively, for 48 h, causes a reduction in immunoreactive Ape1 by approximately 65 and 54%, and an equivalent loss in endonuclease activity. The reduced expression of Ape1 is maintained for up to 5 days after the siRNA in the medium is removed, whereas exposing cultures to scrambled sequence siRNA (SCsiRNA) has no effect of Ape1 protein levels. The reduction in Ape1 significantly reduces cell viability in cultures 24 h after a 1-h exposure to 25-300 microM H2O2, compared to SCsiRNA treated controls. In cells treated with SCsiRNA, exposure to 300 microM H2O2 reduced cell viability by 40 and 30% in hippocampal and sensory neuronal cultures, respectively, whereas cultures treated with Ape1siRNA lost 93 and 80% of cells after the peroxide. Reduced Ape1 levels also increase caspase-3 activity in the cells, 2-3-fold, 60min after a 1-h exposure to 100 microM H2O2 in the cultures. Exposing neuronal cultures with reduced expression of Ape1 to 65 microM H2O2 (hippocampal) or 300 microM H2O2 (sensory) for 1h results in a 3-fold and 1.5-fold increase in the phosphorylation of histone H2A.X compared to cells exposed to SCsiRNA. Overexpressing wild-type Ape1 in hippocampal and sensory cells using adenoviral expression constructs results in significant increase in cell viability after

  9. APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions

    PubMed Central

    Thakur, Shweta; Sarkar, Bibekananda; Cholia, Ravi P; Gautam, Nandini; Dhiman, Monisha; Mantha, Anil K

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme involved in the base excision repair (BER) pathway, which repairs oxidative base damage caused by endogenous and exogenous agents. APE1 acts as a reductive activator of many transcription factors (TFs) and has also been named redox effector factor 1, Ref-1. For example, APE1 activates activator protein-1, nuclear factor kappa B, hypoxia-inducible factor 1α, paired box gene 8, signal transducer activator of transcription 3 and p53, which are involved in apoptosis, inflammation, angiogenesis and survival pathways. APE1/Ref-1 maintains cellular homeostasis (redox) via the activation of TFs that regulate various physiological processes and that crosstalk with redox balancing agents (for example, thioredoxin, catalase and superoxide dismutase) by controlling levels of reactive oxygen and nitrogen species. The efficiency of APE1/Ref-1's function(s) depends on pairwise interaction with participant protein(s), the functions regulated by APE1/Ref-1 include the BER pathway, TFs, energy metabolism, cytoskeletal elements and stress-dependent responses. Thus, APE1/Ref-1 acts as a ‘hub-protein' that controls pathways that are important for cell survival. In this review, we will discuss APE1/Ref-1's versatile nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE/Ref-1. APE1/Ref-1 can be targeted for therapeutic intervention using natural plant products that modulate the expression and functions of APE1/Ref-1. In addition, studies focusing on translational applications based on APE1/Ref-1-mediated therapeutic interventions are discussed. PMID:25033834

  10. Synthetic lethal targeting of DNA double strand break repair deficient cells by human apurinic/apyrimidinic endonuclease (APE1) inhibitors

    PubMed Central

    Sultana, Rebeka; McNeill, Daniel R.; Abbotts, Rachel; Mohammed, Mohammed Z.; Zdzienicka, Małgorzata Z.; Qutob, Haitham; Seedhouse, Claire; Laughton, Charles A.; Fischer, Peter M.; Patel, Poulam M.; Wilson, David M.; Madhusudan, Srinivasan

    2013-01-01

    An apurinic/apyrimidinic (AP) site is an obligatory cytotoxic intermediate in DNA Base Excision Repair (BER) that is processed by human AP endonuclease 1 (APE1). APE1 is essential for BER and an emerging drug target in cancer. We have isolated novel small molecule inhibitors of APE1. In the current study we have investigated the ability of APE1 inhibitors to induce synthetic lethality in a panel of DNA double strand break (DSB) repair deficient and proficient cells; a) Chinese hamster (CH) cells: BRCA2 deficient (V-C8), ATM deficient (V-E5), wild type (V79) and BRCA2 revertant (V-C8(Rev1)). b) Human cancer cells: BRCA1 deficient (MDA-MB-436), BRCA1 proficient (MCF-7), BRCA2 deficient (CAPAN-1 and HeLa SilenciX cells), BRCA2 proficient (PANC1 and control SilenciX cells). We also tested synthetic lethality (SL) in CH ovary cells expressing a dominant–negative form of APE1 (E8 cells) using ATM inhibitors and DNA-PKcs inhibitors (DSB inhibitors). APE1 inhibitors are synthetically lethal in BRCA and ATM deficient cells. APE1 inhibition resulted in accumulation of DNA DSBs and G2/M cell cycle arrest. Synthetic lethality was also demonstrated in CH cells expressing a dominant–negative form of APE1 treated with ATM or DNA-PKcs inhibitors. We conclude that APE1 is a promising synthetic lethality target in cancer. PMID:22377908

  11. Co-circulation of enteroviruses between apes and humans.

    PubMed

    Harvala, Heli; Van Nguyen, Dung; McIntyre, Chloe; Ahuka-Mundeke, Steve; Ngole, Eitel Mpoudi; Delaporte, Eric; Peeters, Martine; Simmonds, Peter

    2014-02-01

    A total of 139 stool samples from wild chimpanzees, gorillas and bonobos in Cameroon and Democratic Republic of Congo (DRC) were screened for enteroviruses (EVs) by reverse transcription PCR. Enterovirus RNA was detected in 10 % of samples, comprising eight from 58 sampled chimpanzees (13.8 %), one from 40 bonobos (2.5 %) and five from 40 gorillas (12.2 %). Three viruses isolated from chimpanzees grouped with human isolate EV-A89 and four (four chimpanzees, one gorilla) represented a newly identified type, EV-A119. These species A virus types overlapped with those circulating in human populations in the same area. The remaining six strains comprised a new species D type, EV-D120, infecting one chimpanzee and four gorillas, and a single EV variant infecting a bonobo that was remarkably divergent from other EVs and potentially constitutes a new enterovirus species. The study demonstrates both the circulation of genetically divergent EV variants in apes and monkeys as well as those shared with local human populations.

  12. Food washing and placer mining in captive great apes.

    PubMed

    Allritz, Matthias; Tennie, Claudio; Call, Josep

    2013-10-01

    Sweet potato washing and wheat placer mining in Japanese macaques (Macaca fuscata) are among the most well known examples of local traditions in non-human animals. The functions of these behaviors and the mechanisms of acquisition and spread of these behaviors have been debated frequently. Prompted by animal caretaker reports that great apes [chimpanzees (Pan troglodytes), bonobos (Pan paniscus), gorillas (Gorilla gorilla), and orangutans (Pongo abelii)] at Leipzig Zoo occasionally wash their food, we conducted a study of food washing behaviors that consisted of two parts. In the first part we assessed the current distribution of the behavior on the basis of caretaker reports. In the second (experimental) part, we provided subjects individually with a water basin and two types of food (apples and cereal) that was either clean or covered/mixed with sand. We found that subjects of all species (except gorillas) placed apples in the water before consumption, and that they did so more often when the apples were dirty than when they were clean. Several chimpanzees and orangutans also engaged in behaviors resembling wheat placer mining.

  13. Danes commemorating Darwin: apes and evolution at the 1909 anniversary.

    PubMed

    Hjermitslev, Hans Henrik

    2010-10-01

    This article analyses the Danish 1909 celebrations of the centenary of Charles Darwin's birth on 12 February 1809. I argue that the 1909 meetings, lectures and publications devoted to Darwin and his theory of evolution by natural selection can be characterised by ambivalence: on the one hand, tribute to a great man of science who established a new view of nature and, on the other hand, scepticism towards the Darwinian mechanism of natural selection and the wider religious and political implications drawn from his theory. The article examines both professional and popular commemorative activities, focusing primarily on celebratory articles carried in widely circulated magazines and newspapers. I identify three types of interpretations of Darwin's ideas which I characterise as 'radical', 'evangelical' and 'safe' science. These different positions were closely linked to the political and cultural divisions of the periodical press. Moreover, my analysis of the popular press offers a solid basis for asserting that to most people Darwinism was associated with human evolution, primarily the relationship between man and apes, while more sophisticated discussions about the crisis of Darwinism prominent among naturalists played only a secondary role in the public arena. This article demonstrates the value of using newspapers as historical sources when looking for public images of Darwin, popular receptions of Darwinism and representations of science in general.

  14. Endothelial cell tumor growth is Ape/ref-1 dependent

    PubMed Central

    Biswas, Ayan; Khanna, Savita; Roy, Sashwati; Pan, Xueliang; Sen, Chandan K.

    2015-01-01

    Tumor-forming endothelial cells have highly elevated levels of Nox-4 that release H2O2 into the nucleus, which is generally not compatible with cell survival. We sought to identify compensatory mechanisms that enable tumor-forming endothelial cells to survive and proliferate under these conditions. Ape-1/ref-1 (Apex-1) is a multifunctional protein that promotes DNA binding of redox-sensitive transcription factors, such as AP-1, and repairs oxidative DNA damage. A validated mouse endothelial cell (EOMA) tumor model was used to demonstrate that Nox-4-derived H2O2 causes DNA oxidation that induces Apex-1 expression. Apex-1 functions as a chaperone to keep transcription factors in a reduced state. In EOMA cells Apex-1 enables AP-1 binding to the monocyte chemoattractant protein-1 (mcp-1) promoter and expression of that protein is required for endothelial cell tumor formation. Intraperitoneal injection of the small molecule inhibitor E3330, which specifically targets Apex-1 redox-sensitive functions, resulted in a 50% decrease in tumor volume compared with mice injected with vehicle control (n = 6 per group), indicating that endothelial cell tumor proliferation is dependent on Apex-1 expression. These are the first reported results to establish Nox-4 induction of Apex-1 as a mechanism promoting endothelial cell tumor formation. PMID:26108661

  15. Are great apes able to reason from multi-item samples to populations of food items?

    PubMed

    Eckert, Johanna; Rakoczy, Hannes; Call, Josep

    2017-10-01

    Inductive learning from limited observations is a cognitive capacity of fundamental importance. In humans, it is underwritten by our intuitive statistics, the ability to draw systematic inferences from populations to randomly drawn samples and vice versa. According to recent research in cognitive development, human intuitive statistics develops early in infancy. Recent work in comparative psychology has produced first evidence for analogous cognitive capacities in great apes who flexibly drew inferences from populations to samples. In the present study, we investigated whether great apes (Pongo abelii, Pan troglodytes, Pan paniscus, Gorilla gorilla) also draw inductive inferences in the opposite direction, from samples to populations. In two experiments, apes saw an experimenter randomly drawing one multi-item sample from each of two populations of food items. The populations differed in their proportion of preferred to neutral items (24:6 vs. 6:24) but apes saw only the distribution of food items in the samples that reflected the distribution of the respective populations (e.g., 4:1 vs. 1:4). Based on this observation they were then allowed to choose between the two populations. Results show that apes seemed to make inferences from samples to populations and thus chose the population from which the more favorable (4:1) sample was drawn in Experiment 1. In this experiment, the more attractive sample not only contained proportionally but also absolutely more preferred food items than the less attractive sample. Experiment 2, however, revealed that when absolute and relative frequencies were disentangled, apes performed at chance level. Whether these limitations in apes' performance reflect true limits of cognitive competence or merely performance limitations due to accessory task demands is still an open question. © 2017 Wiley Periodicals, Inc.

  16. A SYSTEMATIC REVIEW OF THE LITERATURE RELATING TO CAPTIVE GREAT APE MORBIDITY AND MORTALITY.

    PubMed

    Strong, Victoria J; Grindlay, Douglas; Redrobe, Sharon; Cobb, Malcolm; White, Kate

    2016-09-01

    Wild bonobos (Pan paniscus), chimpanzees (Pan troglodytes), Western gorillas (Gorilla gorilla), and orangutans (Pongo pygmaeus, Pongo abelii) are threatened with extinction. In order to help maintain a self-sustaining zoo population, clinicians require a sound understanding of the diseases with which they might be presented. To provide an up-to-date perspective on great ape morbidity and mortality, a systematic review of the zoological and veterinary literature of great apes from 1990 to 2014 was conducted. This is the first review of the great ape literature published since 1990 and the first-ever systematic literature review of great ape morbidity and mortality. The following databases were searched for relevant articles: CAB Abstracts, Web of Science Core Collection, BIOSIS Citation Index, BIOSIS Previews, Current Contents Connect, Data Citation Index, Derwent Innovations Index, MEDLINE, SciELO Citation Index, and Zoological Record. A total of 189 articles reporting on the causes of morbidity and mortality among captive great apes were selected and divided into comparative morbidity-mortality studies and case reports-series or single-disease prevalence studies. The content and main findings of the morbidity-mortality studies were reviewed and the main limitations identified. The case reports-case series and single-disease prevalence studies were categorized and coded according to taxa, etiology, and body system. Subsequent analysis allowed the amount of literature coverage afforded to each category to be calculated and the main diseases and disorders reported within the literature to be identified. This review concludes that reports of idiopathic and infectious diseases along with disorders of the cardiovascular, respiratory, and gastrointestinal body systems were particularly prominent within the great ape literature during 1990-2014. However, recent and accurate prevalence figures are lacking and there are flaws in those reviews that do exist. There is

  17. Evolution of the auditory ossicles in extant hominids: metric variation in African apes and humans

    PubMed Central

    Quam, Rolf M; Coleman, Mark N; Martínez, Ignacio

    2014-01-01

    The auditory ossicles in primates have proven to be a reliable source of phylogenetic information. Nevertheless, to date, very little data have been published on the metric dimensions of the ear ossicles in African apes and humans. The present study relies on the largest samples of African ape ear ossicles studied to date to address questions of taxonomic differences and the evolutionary transformation of the ossicles in gorillas, chimpanzees and humans. Both African ape taxa show a malleus that is characterized by a long and slender manubrium and relatively short corpus, whereas humans show the opposite constellation of a short and thick manubrium and relatively long corpus. These changes in the manubrium are plausibly linked with changes in the size of the tympanic membrane. The main difference between the incus in African apes and humans seems to be related to changes in the functional length. Compared with chimpanzees, human incudes are larger in nearly all dimensions, except articular facet height, and show a more open angle between the axes. The gorilla incus resembles humans more closely in its metric dimensions, including functional length, perhaps as a result of the dramatically larger body size compared with chimpanzees. The differences between the stapedes of humans and African apes are primarily size-related, with humans being larger in nearly all dimensions. Nevertheless, some distinctions between the African apes were found in the obturator foramen and head height. Although correlations between metric variables in different ossicles were generally lower than those between variables in the same bone, variables of the malleus/incus complex appear to be more strongly correlated than those of the incus/stapes complex, perhaps reflecting the different embryological and evolutionary origins of the ossicles. The middle ear lever ratio for the African apes is similar to other haplorhines, but humans show the lowest lever ratio within primates. Very low levels

  18. Evolution of the auditory ossicles in extant hominids: metric variation in African apes and humans.

    PubMed

    Quam, Rolf M; Coleman, Mark N; Martínez, Ignacio

    2014-08-01

    The auditory ossicles in primates have proven to be a reliable source of phylogenetic information. Nevertheless, to date, very little data have been published on the metric dimensions of the ear ossicles in African apes and humans. The present study relies on the largest samples of African ape ear ossicles studied to date to address questions of taxonomic differences and the evolutionary transformation of the ossicles in gorillas, chimpanzees and humans. Both African ape taxa show a malleus that is characterized by a long and slender manubrium and relatively short corpus, whereas humans show the opposite constellation of a short and thick manubrium and relatively long corpus. These changes in the manubrium are plausibly linked with changes in the size of the tympanic membrane. The main difference between the incus in African apes and humans seems to be related to changes in the functional length. Compared with chimpanzees, human incudes are larger in nearly all dimensions, except articular facet height, and show a more open angle between the axes. The gorilla incus resembles humans more closely in its metric dimensions, including functional length, perhaps as a result of the dramatically larger body size compared with chimpanzees. The differences between the stapedes of humans and African apes are primarily size-related, with humans being larger in nearly all dimensions. Nevertheless, some distinctions between the African apes were found in the obturator foramen and head height. Although correlations between metric variables in different ossicles were generally lower than those between variables in the same bone, variables of the malleus/incus complex appear to be more strongly correlated than those of the incus/stapes complex, perhaps reflecting the different embryological and evolutionary origins of the ossicles. The middle ear lever ratio for the African apes is similar to other haplorhines, but humans show the lowest lever ratio within primates. Very low levels

  19. Inhibitors of the apurinic/apyrimidinic endonuclease 1 (APE1)/nucleophosmin (NPM1) interaction that display anti-tumor properties.

    PubMed

    Poletto, Mattia; Malfatti, Matilde C; Dorjsuren, Dorjbal; Scognamiglio, Pasqualina L; Marasco, Daniela; Vascotto, Carlo; Jadhav, Ajit; Maloney, David J; Wilson, David M; Simeonov, Anton; Tell, Gianluca

    2016-05-01

    The apurinic/apyrimidinic endonuclease 1 (APE1) is a protein central to the base excision DNA repair pathway and operates in the modulation of gene expression through redox-dependent and independent mechanisms. Aberrant expression and localization of APE1 in tumors are recurrent hallmarks of aggressiveness and resistance to therapy. We identified and characterized the molecular association between APE1 and nucleophosmin (NPM1), a multifunctional protein involved in the preservation of genome stability and rRNA maturation. This protein-protein interaction modulates subcellular localization and endonuclease activity of APE1. Moreover, we reported a correlation between APE1 and NPM1 expression levels in ovarian cancer, with NPM1 overexpression being a marker of poor prognosis. These observations suggest that tumors that display an augmented APE1/NPM1 association may exhibit increased aggressiveness and resistance. Therefore, targeting the APE1/NPM1 interaction might represent an innovative strategy for the development of anticancer drugs, as tumor cells relying on higher levels of APE1 and NPM1 for proliferation and survival may be more sensitive than untransformed cells. We set up a chemiluminescence-based high-throughput screening assay in order to find small molecules able to interfere with the APE1/NPM1 interaction. This screening led to the identification of a set of bioactive compounds that impair the APE1/NPM1 association in living cells. Interestingly, some of these molecules display anti-proliferative activity and sensitize cells to therapeutically relevant genotoxins. Given the prognostic significance of APE1 and NPM1, these compounds might prove effective in the treatment of tumors that show abundant levels of both proteins, such as ovarian or hepatic carcinomas. © 2015 Wiley Periodicals, Inc.

  20. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury.

    PubMed

    Stetler, R Anne; Gao, Yanqin; Leak, Rehana K; Weng, Zhongfang; Shi, Yejie; Zhang, Lili; Pu, Hongjian; Zhang, Feng; Hu, Xiaoming; Hassan, Sulaiman; Ferguson, Carolyn; Homanics, Gregg E; Cao, Guodong; Bennett, Michael V L; Chen, Jun

    2016-06-21

    A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury.

  1. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury

    PubMed Central

    Stetler, R. Anne; Gao, Yanqin; Leak, Rehana K.; Weng, Zhongfang; Zhang, Lili; Pu, Hongjian; Zhang, Feng; Hu, Xiaoming; Hassan, Sulaiman; Ferguson, Carolyn; Homanics, Gregg E.; Cao, Guodong; Bennett, Michael V. L.; Chen, Jun

    2016-01-01

    A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury. PMID:27274063

  2. Younger apes and human children plan their moves in a maze task.

    PubMed

    Völter, Christoph J; Call, Josep

    2014-02-01

    Planning defined as the predetermination of a sequence of actions towards some goal is crucial for complex problem solving. To shed light on the evolution of executive functions, we investigated the ontogenetic and phylogenetic origins of planning. Therefore, we presented all four great apes species (N=12) as well as 4- and 5-year-old human preschoolers (N=24) with a vertical maze task. To gain a reward placed on the uppermost level of the maze, subjects had to move the reward to the bottom through open gaps situated at each level of the maze. In total, there were ten gaps located over three of the maze's levels, and free passage through these gaps could be flexibly blocked using multiple traps. Due to the decision tree design of the maze, the subjects had to plan their actions depending on the trap configuration up to two steps ahead to successfully retrieve the reward. We found that (1) our measure of planning was negatively correlated with age in nonhuman apes, (2) younger apes as well as 5-year-old children planned their moves up to two steps ahead whereas 4-year-olds were limited to plan one step ahead, and (3) similar performance but different underlying limitations between apes and children. Namely, while all species of nonhuman apes were limited by a lack of motor control, human children exhibited a shortage in shifting their attention across a sequence of subgoals. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Monkeys perform as well as apes and humans in a size discrimination task.

    PubMed

    Schmitt, Vanessa; Kröger, Iris; Zinner, Dietmar; Call, Josep; Fischer, Julia

    2013-09-01

    Whether the cognitive competences of monkeys and apes are rather similar or whether the larger-brained apes outperform monkeys in cognitive experiments is a highly debated topic. Direct comparative analyses are therefore essential to examine similarities and differences among species. We here compared six primate species, including humans, chimpanzees, bonobos, gorillas (great apes), olive baboons, and long-tailed macaques (Old World monkeys) in a task on fine-grained size discrimination. Except for gorillas, subjects of all taxa (i.e. humans, apes, and monkeys) were able to discriminate three-dimensional cubes with a volume difference of only 10 % (i.e. cubes of 50 and 48 mm side length) and performed only slightly worse when the cubes were presented successively. The minimal size discriminated declined further with increasing time delay between presentations of the cubes, highlighting the difficulty to memorize exact size differences. The results suggest that differences in brain size, as a proxy for general cognitive abilities, did not account for variation in performance, but that differential socio-ecological pressures may better explain species differences. Our study highlights the fact that differences in cognitive abilities do not always map neatly onto phylogenetic relationships and that in a number of cognitive experiments monkeys do not fare significantly worse than apes, casting doubt on the assumption that larger brains per se confer an advantage in such kinds of tests.

  4. Sensitivity to Relational Similarity and Object Similarity in Apes and Children.

    PubMed

    Christie, Stella; Gentner, Dedre; Call, Josep; Haun, Daniel Benjamin Moritz

    2016-02-22

    Relational reasoning is a hallmark of sophisticated cognition in humans. Does it exist in other primates? Despite some affirmative answers, there appears to be a wide gap in relational ability between humans and other primates--even other apes. Here, we test one possible explanation for this gap, motivated by developmental research showing that young humans often fail at relational reasoning tasks because they focus on objects instead of relations. When asked, "duck:duckling is like tiger:?," preschool children choose another duckling (object match) rather than a cub. If other apes share this focus on concrete objects, it could undermine their relational reasoning in similar ways. To test this, we compared great apes and 3-year-old humans' relational reasoning on the same spatial mapping task, with and without competing object matches. Without competing object matches, both children and Pan species (chimpanzees and bonobos) spontaneously used relational similarity, albeit children more so. But when object matches were present, only children responded strongly to them. We conclude that the relational gap is not due to great apes' preference for concrete objects. In fact, young humans show greater object focus than nonhuman apes.

  5. Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk

    PubMed Central

    AlMutairi, Fatima; Ali Khan Pathan, Akbar; Alanazi, Mohammed; Shalaby, Manal; Alabdulkarim, Huda A.; Alamri, Abdullah; Al Naeem, Abdulrahman; Elrobh, Moammad; Shaik, Jilani P.; Khan, Wajahatullah; Khan, Zahid; Reddy Parine, Narasimha

    2015-01-01

    Objective. The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population. Methods. We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation. Results. Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk. Conclusion. Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population. PMID:26257461

  6. Structure of yeast Ape1 and its role in autophagic vesicle formation

    PubMed Central

    Su, Ming-Yuan; Peng, Wen-Hsin; Ho, Meng-Ru; Su, Shih-Chieh; Chang, Yuan-Chih; Chen, Guang-Chao; Chang, Chung-I

    2015-01-01

    In Saccharomyces cerevisiae, a constitutive biosynthetic transport pathway, termed the cytoplasm-to-vacuole targeting (Cvt) pathway, sequesters precursor aminopeptidase I (prApe1) dodecamers in the form of a large complex into a Cvt vesicle using autophagic machinery, targeting it into the vacuole (the yeast lysosome) where it is proteolytically processed into its mature form, Ape1, by removal of an amino-terminal 45-amino acid propeptide. prApe1 is thought to serve as a scaffolding cargo critical for the assembly of the Cvt vesicle by presenting the propeptide to mediate higher-ordered complex formation and autophagic receptor recognition. Here we report the X-ray crystal structure of Ape1 at 2.5 Å resolution and reveal its dodecameric architecture consisting of dimeric and trimeric units, which associate to form a large tetrahedron. The propeptide of prApe1 exhibits concentration-dependent oligomerization and forms a stable tetramer. Structure-based mutagenesis demonstrates that disruption of the inter-subunit interface prevents dodecameric assembly and vacuolar targeting in vivo despite the presence of the propeptide. Furthermore, by examining the vacuolar import of propeptide-fused exogenous protein assemblies with different quaternary structures, we found that 3-dimensional spatial distribution of propeptides presented by a scaffolding cargo is essential for the assembly of the Cvt vesicle for vacuolar delivery. This study describes a molecular framework for understanding the mechanism of Cvt or autophagosomal biogenesis in selective macroautophagy. PMID:26208681

  7. Young children spontaneously invent wild great apes' tool-use behaviours.

    PubMed

    Reindl, E; Beck, S R; Apperly, I A; Tennie, C

    2016-02-24

    The variety and complexity of human-made tools are unique in the animal kingdom. Research investigating why human tool use is special has focused on the role of social learning: while non-human great apes acquire tool-use behaviours mostly by individual (re-)inventions, modern humans use imitation and teaching to accumulate innovations over time. However, little is known about tool-use behaviours that humans can invent individually, i.e. without cultural knowledge. We presented 2- to 3.5-year-old children with 12 problem-solving tasks based on tool-use behaviours shown by great apes. Spontaneous tool use was observed in 11 tasks. Additionally, tasks which occurred more frequently in wild great apes were also solved more frequently by human children. Our results demonstrate great similarity in the spontaneous tool-use abilities of human children and great apes, indicating that the physical cognition underlying tool use shows large overlaps across the great ape species. This suggests that humans are neither born with special physical cognition skills, nor that these skills have degraded due to our species' long reliance of social learning in the tool-use domain.

  8. A reassessment of living hominoid postcranial variability: implications for ape evolution.

    PubMed

    Young, Nathan M

    2003-12-01

    In an analysis of hominoid postcranial variation, 'Evol. Anthrop. 6 (1998) 87' argued that many purportedly unique features of the hominoid postcranium are actually much more variable than previously reported and in many instances overlap with both suspensory (Ateles) and non-suspensory primates. Based on these results, it was concluded that parallelism in the living ape postcranium was a plausible and even likely possibility given the Miocene hominoid postcranial record. However, this analysis did not distinguish whether within-hominoid variability or overlap with non-hominoids involved one or all ape taxa, a distinction which has potentially important effects on the interpretation of results. To address this issue, primate postcranial morphometric data from the trunk and forelimb were reanalyzed using three techniques: cladistic analysis, principle components analysis, and cluster analysis. Results reveal that these postcranial characters distinguish not only suspensory and quadrupedal primates but also discriminate hominoids and Ateles from all other taxa, great apes from lesser apes and Ateles, cercopithecines from colobines, and cercopithecoids from platyrrhines. The majority of hominoid variability and overlap with Ateles occurs with Hylobates humeral head and shoulder joint characters related to brachiation. This suggests that Hylobates' specializations may skew analyses of hominoid postcranial uniqueness and variability, and that great apes are relatively similar in their postcranium.

  9. Spontaneous use of tools as straws in great apes.

    PubMed

    Manrique, Héctor Marín; Call, Josep

    2011-03-01

    Great apes can use multiple tools to extract food embedded in substrates and can invent new ways to exploit those resources. We tested five bonobos, five chimpanzees, and six orangutans in a task in which they had to use (and modify) a tool as a straw to drink the juice located inside a container. Experiment 1 showed that four orangutans and one chimpanzee invented the use of a piece of electric cable to get the juice. Experiment 2 investigated whether subjects could transform a non-functional hose into a functional one by removing blockages that impeded the free flow of juice. Orangutans outperformed chimpanzees and bonobos by differentially removing those blockages that prevented the flow of juice, often doing so before attempting to extract the juice. In Experiment 3, we presented chimpanzees and orangutans with four 3-tool sets (each tool set contained a single straw-like tool) and allowed them to select one tool. Unlike chimpanzees, orangutans succeeded in selecting the straw-like tool above chance levels without having to physically manipulate it. We suggest that orangutans' superior performance is related to their greater reliance on mouth actions during foraging. Experiment 4 investigated whether orangutans were also capable of selecting the suitable tool not by its appearance, but by the effects that it produced. After witnessing the experimenter blow bubbles or absorb liquid with a functional tool but fail to accomplish the same thing with the non-functional tool, orangutans failed to select the functional tool above chance levels. © Springer-Verlag 2010

  10. Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting.

    PubMed Central

    Jauch, A; Wienberg, J; Stanyon, R; Arnold, N; Tofanelli, S; Ishida, T; Cremer, T

    1992-01-01

    The homology between hylobatid chromosomes and other primates has long remained elusive. We used chromosomal in situ suppression hybridization of all human chromosome-specific DNA libraries to "paint" the chromosomes of primates and establish homologies between the human, great ape (chimpanzee, gorilla, and orangutan), and gibbon karyotypes (Hylobates lar species group, 2n = 44). The hybridization patterns unequivocally demonstrate the high degree of chromosomal homology and synteny of great ape and human chromosomes. Relative to human, no translocations were detected in great apes, except for the well-known fusion-origin of human chromosome 2 and a 5;17 translocation in the gorilla. In contrast, numerous translocations were detected that have led to the massive reorganization of the gibbon karyotype: the 22 autosomal human chromosomes have been divided into 51 elements to compose the 21 gibbon autosomes. Molecular cytogenetics promises to finally allow hylobatids to be integrated into the overall picture of chromosomal evolution in the primates. Images PMID:1528869

  11. Constraints on great apes' imitation: model and action selectivity in rehabilitant orangutan (Pongo pygmaeus) imitation.

    PubMed

    Russon, A E; Galdikas, B M

    1995-03-01

    We discuss selectivity in great ape imitation, on the basis of an observational study of spontaneous imitation in free-ranging rehabilitant orangutans (Pongo pygmaeus). Research on great ape imitation has neglected selectivity, although comparative evidence suggests it may be important. We observed orangutans in central Indonesian Borneo and assessed patterns in the models and actions they spontaneously imitated. The patterns we found resembled those reported in humans. Orangutans preferred models with whom they had positive affective relationships (e.g., important caregiver or older sibling) and actions that reflected their current competence, were receptively familiar, and were relevant to tasks that faced them. Both developmental and individual variability were found. We discuss the probable functions of imitation for great apes and the role of selectivity in directing it. We also make suggestions for more effective elicitation of imitation.

  12. Chimpanzee fauna isotopes provide new interpretations of fossil ape and hominin ecologies.

    PubMed

    Nelson, Sherry V

    2013-12-22

    Carbon and oxygen stable isotopes within modern and fossil tooth enamel record the aspects of an animal's diet and habitat use. This investigation reports the first isotopic analyses of enamel from a large chimpanzee community and associated fauna, thus providing a means of comparing fossil ape and early hominin palaeoecologies with those of a modern ape. Within Kibale National Park forest, oxygen isotopes differentiate primate niches, allowing for the first isotopic reconstructions of degree of frugivory versus folivory as well as use of arboreal versus terrestrial resources. In a comparison of modern and fossil community isotopic profiles, results indicate that Sivapithecus, a Miocene ape from Pakistan, fed in the forest canopy, as do chimpanzees, but inhabited a forest with less continuous canopy or fed more on leaves. Ardipithecus, an early hominin from Ethiopia, fed both arboreally and terrestrially in a more open habitat than inhabited by chimpanzees.

  13. Great apes distinguish true from false beliefs in an interactive helping task.

    PubMed

    Buttelmann, David; Buttelmann, Frances; Carpenter, Malinda; Call, Josep; Tomasello, Michael

    2017-01-01

    Understanding the behavior of others in a wide variety of circumstances requires an understanding of their psychological states. Humans' nearest primate relatives, the great apes, understand many psychological states of others, for example, perceptions, goals, and desires. However, so far there is little evidence that they possess the key marker of advanced human social cognition: an understanding of false beliefs. Here we demonstrate that in a nonverbal (implicit) false-belief test which is passed by human 1-year-old infants, great apes as a group, including chimpanzees (Pan troglodytes), bonobos (Pan paniscus), and orangutans (Pongo abelii), distinguish between true and false beliefs in their helping behavior. Great apes thus may possess at least some basic understanding that an agent's actions are based on her beliefs about reality. Hence, such understanding might not be the exclusive province of the human species.

  14. Brief communication: Swimming and diving behavior in apes (Pan troglodytes and Pongo pygmaeus): first documented report.

    PubMed

    Bender, Renato; Bender, Nicole

    2013-09-01

    Extant hominoids, including humans, are well known for their inability to swim instinctively. We report swimming and diving in two captive apes using visual observation and video recording. One common chimpanzee and one orangutan swam repeatedly at the water surface over a distance of 2-6 m; both individuals submerged repeatedly. We show that apes are able to overcome their negative buoyancy by deliberate swimming, using movements which deviate from the doggy-paddle pattern observed in other primates. We suggest that apes' poor swimming ability is due to behavioral, anatomical, and neuromotor changes related to an adaptation to arboreal life in their early phylogeny. This strong adaptive focus on arboreal life led to decreased opportunities to interact with water bodies and consequently to a reduction of selective pressure to maintain innate swimming behavior. As the doggy paddle is associated with quadrupedal walking, a deviation from terrestrial locomotion might have interfered with the fixed rhythmic action patterns responsible for innate swimming.

  15. Chimpanzee fauna isotopes provide new interpretations of fossil ape and hominin ecologies

    PubMed Central

    Nelson, Sherry V.

    2013-01-01

    Carbon and oxygen stable isotopes within modern and fossil tooth enamel record the aspects of an animal's diet and habitat use. This investigation reports the first isotopic analyses of enamel from a large chimpanzee community and associated fauna, thus providing a means of comparing fossil ape and early hominin palaeoecologies with those of a modern ape. Within Kibale National Park forest, oxygen isotopes differentiate primate niches, allowing for the first isotopic reconstructions of degree of frugivory versus folivory as well as use of arboreal versus terrestrial resources. In a comparison of modern and fossil community isotopic profiles, results indicate that Sivapithecus, a Miocene ape from Pakistan, fed in the forest canopy, as do chimpanzees, but inhabited a forest with less continuous canopy or fed more on leaves. Ardipithecus, an early hominin from Ethiopia, fed both arboreally and terrestrially in a more open habitat than inhabited by chimpanzees. PMID:24197413

  16. Differences in the nonverbal requests of great apes and human infants.

    PubMed

    van der Goot, Marloes H; Tomasello, Michael; Liszkowski, Ulf

    2014-01-01

    This study investigated how great apes and human infants use imperative pointing to request objects. In a series of three experiments (infants, N = 44; apes, N = 12), subjects were given the opportunity to either point to a desired object from a distance or else to approach closer and request it proximally. The apes always approached close to the object, signaling their request through instrumental actions. In contrast, the infants quite often stayed at a distance, directing the experimenters' attention to the desired object through index-finger pointing, even when the object was in the open and they could obtain it by themselves. Findings distinguish 12-month-olds' imperative pointing from ontogenetic and phylogenetic earlier forms of ritualized reaching. © 2013 The Authors. Child Development © 2013 Society for Research in Child Development, Inc.

  17. CXCR4 homologues of gibbon ape, African green monkey, squirrel monkey, and cotton-top marmoset.

    PubMed

    Zubair, S; Metzenberg, S

    2000-08-10

    CXCR4 gene homologues were isolated from an ape (gibbon), an Old World monkey (African green monkey), and two New World monkeys (squirrel monkey and cotton-top marmoset), and their DNA sequences determined. The squirrel monkey and cotton-top marmoset CXCR4 sequences more closely resemble homologues from apes than Old World monkeys, a pattern not seen for the related chemokine receptor CCR5. The African green monkey CXCR4 gene is similar to its homologue in baboon, a pattern that has also been seen among CCR5 homologues. The gibbon CXCR4 contains the first polymorphisms recognized in ape homologues, the human and chimpanzee CXCR4 proteins being identical, and two of these three differences are also observed in one or more Old World monkey homologues. While 18 positions within CXCR4 are now known to be polymorphic in primates, 7 of these polymorphisms have been observed in multiple examples and 11 have been observed only once.

  18. The role of socio-communicative rearing environments in the development of social and physical cognition in apes.

    PubMed

    Russell, Jamie L; Lyn, Heidi; Schaeffer, Jennifer A; Hopkins, William D

    2011-11-01

    The cultural intelligence hypothesis (CIH) claims that humans' advanced cognition is a direct result of human culture and that children are uniquely specialized to absorb and utilize this cultural experience (Tomasello, 2000). Comparative data demonstrating that 2.5-year-old human children outperform apes on measures of social cognition but not on measures of physical cognition support this claim (Herrmann et al., 2007). However, the previous study failed to control for rearing when comparing these two species. Specifically, the human children were raised in a human culture whereas the apes were raised in standard sanctuary settings. To further explore the CIH, here we compared the performance on multiple measures of social and physical cognition in a group of standard reared apes raised in conditions typical of zoo and biomedical laboratory settings to that of apes reared in an enculturated socio-communicatively rich environment. Overall, the enculturated apes significantly outperformed their standard reared counterparts on the cognitive tasks and this was particularly true for measures of communication. Furthermore, the performance of the enculturated apes was very similar to previously reported data from 2.5-year-old children. We conclude that apes who are reared in a human-like socio-communicatively rich environment develop superior communicative abilities compared to apes reared in standard laboratory settings, which supports some assumptions of the cultural intelligence hypothesis. 2011 Blackwell Publishing Ltd.

  19. The APE1 Asp/Asp genotype and the combination of APE1 Asp/Asp and hOGG1-Cys variants are associated with increased p53 mutation in non-small cell lung cancer.

    PubMed

    Lin, Chun-Hsuan; Chen, Po-Ming; Cheng, Ya-Wen; Chen, Chih-Yi; Yuan, Chiun-Jye; Lee, Huei

    2012-01-01

    The hOGG1 Ser326Cys polymorphism is associated with lung cancer risk, but there are limited data regarding an association between the APE1 Asp148Glu polymorphism and lung cancer. Biological evidence shows that the hOGG1-Cys allele results in less DNA repair activity; however, this is not associated with p53 mutation in lung cancer. Therefore, we investigated whether an interaction between hOGG1 and APE1 is associated with the frequency of p53 mutation in lung cancer. We studied 217 Taiwanese adults with primary lung cancer. DNA polymorphisms of hOGG1 and APE1 were determined by polymerase chain reaction (PCR)-based restriction fragment length polymorphism. Mutations in p53 exons 5-8 were detected by direct sequencing. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the risk of p53 mutation associated with polymorphisms of hOGG1 and APE1 in lung cancer. As expected, no association between hOGG1 polymorphism and p53 mutation was observed in this population. However, a higher risk of p53 mutation was found in participants with the APE1 Asp/Asp genotype than in those with the APE1-Glu allele (OR, 2.15; 95% CI, 1.19-3.87; P = 0.011). The risk of p53 mutation was also higher in participants with APE1 Asp/Asp plus hOGG1-Cys than in those with APE1-Glu plus hOGG1 Ser/Ser (OR, 3.72; 95% CI, 1.33-10.40; P = 0.012). These results suggest that the APE1 Asp/Asp genotype and the combination of the APE1 Asp/Asp and hOGG1-Cys variants are associated with increased risk of p53 mutation in non-small cell lung cancer.

  20. Size and scaling in the mandible of living and extinct apes.

    PubMed

    Ravosa, M J

    2000-01-01

    The purpose of this study is to fill a gap in our knowledge of dietary and allometric determinants of masticatory function and mandibular morphology in major catarrhine clades. To extend the implications of previous work on variation in mandibular form and function in other primates, a scaling analysis was performed on 20 extinct and 7 living non-cercopithecoid catarrhines or 'dental apes'. Results of allometric comparisons indicate that for a given jaw length, larger apes exhibit significantly more robust corpora and symphyses than smaller forms. This appears linked to size-related increases in dietary toughness and/or hardness, which in turn causes elevated mandibular loads and/or greater repetitive loading during unilateral mastication. Larger-bodied dental apes also display more curved symphyses, which also explains the positive allometry of symphysis width and height. In apes, proconsulids often evince more robust jaws while all hylobatids, Pan and Dryopithecus laietanus possess more gracile cross sections. In propliopithecids, Aegyptopithecus is always more robust than Propliopithecus. In proconsulids, Rangwapithecus and Micropithecus commonly exhibit more robust jaws whereas Dendropithecus and especially Simiolus are more gracile. Most of the larger taxa are folivorous and/or hard-object frugivorous pongids with relatively larger dentaries. Though apes have relatively wider corpora than cercopithecines due to greater axial twisting of the corpora during chewing, they are otherwise alike in robusticity levels. Smaller apes are similar to cercopithecines in evincing a relatively high degree of symphyseal curvature, while larger taxa are like colobines in having less curvature. Larger pongids resemble or even exceed colobine jaw proportions and thus appear to converge on colobines in terms of the mechanical properties of their diets.

  1. Cognitive inferences in fossil apes (Primates, Hominoidea): does encephalization reflect intelligence?

    PubMed

    Alba, David M

    2010-01-01

    Paleobiological inferences on general cognitive abilities (intelligence) in fossil hominoids strongly rely on relative brain size or encephalization, computed by means of allometric residuals, quotients or constants. Th is has been criticized on the basis that it presumably fails to reflect the higher intelligence of great apes, and absolute brain size has been favored instead. Many problems of encephalization metrics stem from the decrease of allometric slopes towards lower taxonomic level, thus making it difficult to determine at what level encephalization metrics have biological meaning. Here, the hypothesis that encephalization can be used as a good neuroanatomical proxy for intelligence is tested at two different taxonomic levels. A significant correlation is found between intelligence and encephalization only at a lower taxonomic level, i.e. on the basis of a low allometric slope, irrespective of whether species data or independent contrasts are employed. This indicates that higher-level slopes, resulting from encephalization grade shifts between subgroups (including hylobatids vs. great apes), do not reflect functional equivalence, whereas lower-level metrics can be employed as a paleobiological proxy for intelligence. Thus, in accordance to intelligence rankings, lower-level metrics indicate that great apes are more encephalized than both monkeys and hylobatids. Regarding fossil taxa, encephalization increased during hominin evolution (particularly in Homo), but during the Miocene a significant shift towards higher encephalization (and inferred enhanced cognitive abilities) must have been also involved in the emergence of the great-ape-and-human clade (Hominidae). This is confirmed by the modern great-ape-like degree of encephalization displayed by the fossil great ape Hispanopithecus, which contrasts with the rather hylobatid-like degree of the stem hominoid Proconsul. The similarly low encephalization of Oreopithecus might result from secondary reduction

  2. Thyroid autoantibodies are rare in nonhuman great apes and hypothyroidism cannot be attributed to thyroid autoimmunity.

    PubMed

    Aliesky, Holly; Courtney, Cynthia L; Rapoport, Basil; McLachlan, Sandra M

    2013-12-01

    The great apes include, in addition to Homo, the genera Pongo (orangutans), Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes (chimpanzees) and P. paniscus (bonobos). Adult-onset hypothyroidism was previously reported in 4 individual nonhuman great apes. However, there is scarce information on normal serum thyroid hormone levels and virtually no data for thyroid autoantibodies in these animals. Therefore, we examined thyroid hormone levels and TSH in all nonhuman great ape genera including adults, adolescents, and infants. Because hypothyroidism in humans is commonly the end result of thyroid autoimmunity, we also tested healthy and hypothyroid nonhuman great apes for antibodies to thyroglobulin (Tg), thyroid peroxidase (TPO), and the TSH receptor (TSHR). We established a thyroid hormone and TSH database in orangutans, gorillas, chimpanzees, and bonobos (447 individuals). The most striking differences are the greatly reduced free-T4 and free-T3 levels in orangutans and gorillas vs chimpanzees and bonobos, and conversely, elevated TSH levels in gorillas vs Pan species. Antibodies to Tg and TPO were detected in only 2.6% of adult animals vs approximately 10% in humans. No animals with Tg, TPO, or TSHR antibodies exhibited thyroid dysfunction. Conversely, hypothyroid nonhuman great apes lacked thyroid autoantibodies. Moreover, thyroid histology in necropsy tissues was similar in euthyroid and hypothyroid individuals, and lymphocytic infiltration was absent in 2 hypothyroid animals. In conclusion, free T4 and free T3 are lower in orangutans and gorillas vs chimpanzees and bonobos, the closest living human relatives. Moreover, thyroid autoantibodies are rare and hypothyroidism is unrelated to thyroid autoimmunity in nonhuman great apes.

  3. Great Apes Make Anticipatory Looks Based on Long-Term Memory of Single Events.

    PubMed

    Kano, Fumihiro; Hirata, Satoshi

    2015-10-05

    Everyday life poses a continuous challenge for individuals to encode ongoing events, retrieve past events, and predict impending events [1-4]. Attention and eye movements reflect such online cognitive and memory processes [5, 6], especially through "anticipatory looks" [7-10]. Previous studies have demonstrated the ability of nonhuman animals to retrieve detailed information about single events that happened in the distant past [11-20]. However, no study has tested whether nonhuman animals employ online memory processes, in which they encode ongoing movie-like events into long-term storage during single viewing experiences. Here, we developed a novel eye-tracking task to examine great apes' anticipatory looks to the events that they had encountered one time 24 hr earlier. Half-minute movie clips depicted novel and potentially alarming situations to the participant apes (six bonobos, six chimpanzees). In the experiment 1 clip, an aggressive ape-like character came out from one of two identical doors. While viewing the same movie again, apes anticipatorily looked at the door where the character would show up. In the experiment 2 clip, the human actor grabbed one of two objects and attacked the character with it. While viewing the same movie again but with object-location switched, apes anticipatorily looked at the object that the human would use, rather than the former location of the object. Our results thus show that great apes, just by watching the events once, encoded particular information (location and content) into long-term memory and later retrieved that information at a particular time in anticipation of the impending events. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Great apes and children infer causal relations from patterns of variation and covariation.

    PubMed

    Völter, Christoph J; Sentís, Inés; Call, Josep

    2016-10-01

    We investigated whether nonhuman great apes (N=23), 2.5-year-old (N=20), and 3-year-old children (N=40) infer causal relations from patterns of variation and covariation by adapting the blicket detector paradigm for apes. We presented chimpanzees (Pan troglodytes), bonobos (Pan paniscus), orangutans (Pongo abelii), gorillas (Gorilla gorilla), and children (Homo sapiens) with a novel reward dispenser, the blicket detector. The detector was activated by inserting specific (yet randomly determined) objects, the so-called blickets. Once activated a reward was released, accompanied by lights and a short tone. Participants were shown different patterns of variation and covariation between two different objects and the activation of the detector. When subsequently choosing between one of the two objects to activate the detector on their own all species, except gorillas (who failed the training), took these patterns of correlation into account. In particular, apes and 2.5-year-old children ignored objects whose effect on the detector completely depended on the presence of another object. Follow-up experiments explored whether the apes and children were also able to re-evaluate evidence retrospectively. Only children (3-year-olds in particular) were able to make such retrospective inferences about causal structures from observing the effects of the experimenter's actions. Apes succeeded here only when they observed the effects of their own interventions. Together, this study provides evidence that apes, like young children, accurately infer causal structures from patterns of (co)variation and that they use this information to inform their own interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Consequences of Non-Intervention for Infectious Disease in African Great Apes

    PubMed Central

    Ryan, Sadie J.; Walsh, Peter D.

    2011-01-01

    Infectious disease has recently joined poaching and habitat loss as a major threat to African apes. Both “naturally” occurring pathogens, such as Ebola and Simian Immunodeficiency Virus (SIV), and respiratory pathogens transmitted from humans, have been confirmed as important sources of mortality in wild gorillas and chimpanzees. While awareness of the threat has increased, interventions such as vaccination and treatment remain controversial. Here we explore both the risk of disease to African apes, and the status of potential responses. Through synthesis of published data, we summarize prior disease impact on African apes. We then use a simple demographic model to illustrate the resilience of a well-known gorilla population to disease, modeled on prior documented outbreaks. We found that the predicted recovery time for this specific gorilla population from a single outbreak ranged from 5 years for a low mortality (4%) respiratory outbreak, to 131 years for an Ebola outbreak that killed 96% of the population. This shows that mortality rates comparable to those recently reported for disease outbreaks in wild populations are not sustainable. This is particularly troubling given the rising pathogen risk created by increasing habituation of wild apes for tourism, and the growth of human populations surrounding protected areas. We assess potential future disease spillover risk in terms of vaccination rates amongst humans that may come into contact with wild apes, and the availability of vaccines against potentially threatening diseases. We discuss and evaluate non-interventionist responses such as limiting tourist access to apes, community health programs, and safety, logistic, and cost issues that constrain the potential of vaccination. PMID:22216162

  6. Thyroid Autoantibodies Are Rare in Nonhuman Great Apes and Hypothyroidism Cannot Be Attributed to Thyroid Autoimmunity

    PubMed Central

    Aliesky, Holly; Courtney, Cynthia L.; Rapoport, Basil

    2013-01-01

    The great apes include, in addition to Homo, the genera Pongo (orangutans), Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes (chimpanzees) and P. paniscus (bonobos). Adult-onset hypothyroidism was previously reported in 4 individual nonhuman great apes. However, there is scarce information on normal serum thyroid hormone levels and virtually no data for thyroid autoantibodies in these animals. Therefore, we examined thyroid hormone levels and TSH in all nonhuman great ape genera including adults, adolescents, and infants. Because hypothyroidism in humans is commonly the end result of thyroid autoimmunity, we also tested healthy and hypothyroid nonhuman great apes for antibodies to thyroglobulin (Tg), thyroid peroxidase (TPO), and the TSH receptor (TSHR). We established a thyroid hormone and TSH database in orangutans, gorillas, chimpanzees, and bonobos (447 individuals). The most striking differences are the greatly reduced free-T4 and free-T3 levels in orangutans and gorillas vs chimpanzees and bonobos, and conversely, elevated TSH levels in gorillas vs Pan species. Antibodies to Tg and TPO were detected in only 2.6% of adult animals vs approximately 10% in humans. No animals with Tg, TPO, or TSHR antibodies exhibited thyroid dysfunction. Conversely, hypothyroid nonhuman great apes lacked thyroid autoantibodies. Moreover, thyroid histology in necropsy tissues was similar in euthyroid and hypothyroid individuals, and lymphocytic infiltration was absent in 2 hypothyroid animals. In conclusion, free T4 and free T3 are lower in orangutans and gorillas vs chimpanzees and bonobos, the closest living human relatives. Moreover, thyroid autoantibodies are rare and hypothyroidism is unrelated to thyroid autoimmunity in nonhuman great apes. PMID:24092641

  7. Human Apurinic/Apyrimidinic Endonuclease (APE1) Is Acetylated at DNA Damage Sites in Chromatin, and Acetylation Modulates Its DNA Repair Activity

    PubMed Central

    Roychoudhury, Shrabasti; Nath, Somsubhra; Song, Heyu; Hegde, Muralidhar L.; Bellot, Larry J.; Mantha, Anil K.; Sengupta, Shiladitya; Ray, Sutapa; Natarajan, Amarnath

    2016-01-01

    ABSTRACT Apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome, inhibit transcription and block replication. The primary enzyme that repairs AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the base excision repair (BER) pathway. Although the mechanism by which APE1 repairs AP sites in vitro has been extensively investigated, it is largely unknown how APE1 repairs AP sites in cells. Here, we show that APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle. Positive charges of acetylable lysine residues in the N-terminal domain of APE1 are essential for chromatin association. Acetylation-mediated neutralization of the positive charges of the lysine residues in the N-terminal domain of APE1 induces a conformational change; this in turn enhances the AP endonuclease activity of APE1. In the absence of APE1 acetylation, cells accumulated AP sites in the genome and showed higher sensitivity to DNA-damaging agents. Thus, mammalian cells, unlike Saccharomyces cerevisiae or Escherichia coli cells, require acetylation of APE1 for the efficient repair of AP sites and base damage in the genome. Our study reveals that APE1 acetylation is an integral part of the BER pathway for maintaining genomic integrity. PMID:27994014

  8. Does early care affect joint attention in great apes (Pan troglodytes, Pan paniscus, Pongo abelii, Pongo pygmaeus, Gorilla gorilla)?

    PubMed

    Pitman, Caisie A; Shumaker, Robert W

    2009-08-01

    The ability to share attention with another is the foundation on which other theory of mind skills are formed. The quality of care received during infancy has been correlated with increased joint attention in humans. The purpose of this study was to assess the effects of care style (responsive or basic) and caregiver type (ape or human) during the first 6 months on joint attention in 4 great ape species (Pan troglodytes, Gorilla gorilla, Pongo spp., and Pan pansicus). Great apes engaged in joint attention with conspecifics and humans regardless of the style of early care they experienced from either a great ape mother or human caregiver. This finding suggests that joint attention is a robust ability in great apes that is resilient against at least some differences in early care. Future studies using additional measures of early care quality are recommended.

  9. Samuel Fernberger's rejected doctoral dissertation: a neglected resource for the history of ape research in America.

    PubMed

    Dewsbury, Donald A

    2009-02-01

    I summarize a never-completed 1911 doctoral dissertation on ape behavior by Samuel Fernberger of the University of Pennsylvania. Included are observations on many behavioral patterns including sensory and perceptual function, learning, memory, attention, imagination, personality, and emotion in an orangutan and two chimpanzees. There are examples of behavior resembling insight, conscience, tool use and imitation. Language comprehension was good but speech production was minimal. The document appears to contradict a brief published article on the project by William Furness in that punishment was frequently used. The document is important for understanding Fernberger's early career, for anticipations of later research, and for understanding the status of ape research at the time.

  10. The mentality of crows: convergent evolution of intelligence in corvids and apes.

    PubMed

    Emery, Nathan J; Clayton, Nicola S

    2004-12-10

    Discussions of the evolution of intelligence have focused on monkeys and apes because of their close evolutionary relationship to humans. Other large-brained social animals, such as corvids, also understand their physical and social worlds. Here we review recent studies of tool manufacture, mental time travel, and social cognition in corvids, and suggest that complex cognition depends on a "tool kit" consisting of causal reasoning, flexibility, imagination, and prospection. Because corvids and apes share these cognitive tools, we argue that complex cognitive abilities evolved multiple times in distantly related species with vastly different brain structures in order to solve similar socioecological problems.

  11. The role of "the aquatic" in human evolution: constraining the aquatic ape hypothesis.

    PubMed

    Foley, Robert; Lahr, Marta Mirazón

    2014-01-01

    Few things show the distinctiveness of human evolution research better than the Aquatic Ape Hypothesis (AAH). On one hand, we have "orthodox" research into human evolution, firmly based on land; on the other, we have the aquatic ape community, convinced not only that our ancestors went through an aquatic phase, but that the professional scientific community ignores their work and keeps it out of the mainstream. How many fields of science have two entirely parallel communities that essentially are hermetically sealed from each other?

  12. dAPE: a web server to detect homorepeats and follow their evolution.

    PubMed

    Mier, Pablo; Andrade-Navarro, Miguel A

    2017-04-15

    Homorepeats are low complexity regions consisting of repetitions of a single amino acid residue. There is no current consensus on the minimum number of residues needed to define a functional homorepeat, nor even if mismatches are allowed. Here we present dAPE, a web server that helps following the evolution of homorepeats based on orthology information, using a sensitive but tunable cutoff to help in the identification of emerging homorepeats. dAPE can be accessed from http://cbdm-01.zdv.uni-mainz.de/∼munoz/polyx . munoz@uni-mainz.de. Supplementary data are available at Bioinformatics online.

  13. Dyadic brain modelling, mirror systems and the ontogenetic ritualization of ape gesture

    PubMed Central

    Arbib, Michael; Ganesh, Varsha; Gasser, Brad

    2014-01-01

    The paper introduces dyadic brain modelling, offering both a framework for modelling the brains of interacting agents and a general framework for simulating and visualizing the interactions generated when the brains (and the two bodies) are each coded up in computational detail. It models selected neural mechanisms in ape brains supportive of social interactions, including putative mirror neuron systems inspired by macaque neurophysiology but augmented by increased access to proprioceptive state. Simulation results for a reduced version of the model show ritualized gesture emerging from interactions between a simulated child and mother ape. PMID:24778382

  14. The Aqua-Planet Experiment (APE): CONTROL SST Simulation

    NASA Technical Reports Server (NTRS)

    Blackburn, Michael; Williamson, David L.; Nakajima, Kensuke; Ohfuchi, Wataru; Takahashi, Yoshiyuki O.; Hayashi, Yoshi-Yuki; Nakamura, Hisashi; Ishiwatari, Masaki; Mcgregor, John L.; Borth, Hartmut; Wirth, Volkmar; Frank, Helmut; Bechtold, Peter; Wedi, Nils P.; Tomita, Hirofumi; Satoh, Masaki; Zhao, Ming; Held, Isaac M.; Suarez, Max J.; Lee, Myong-In; Watanabe, Masahiro; Kimoto, Masahide; Liu, Yimin; Wang, Zaizhi; Molod, Andrea M.; Rajendran, Kavirajan; Kotoh, Akio; Stratton, Rachel

    2013-01-01

    Climate simulations by 16 atmospheric general circulation models (AGCMs) are compared on an aqua-planet, a water-covered Earth with prescribed sea surface temperature varying only in latitude. The idealised configuration is designed to expose differences in the circulation simulated by different models. Basic features of the aqua-planet climate are characterised by comparison with Earth. The models display a wide range of behaviour. The balanced component of the tropospheric mean flow, and mid-latitude eddy covariances subject to budget constraints, vary relatively little among the models. In contrast, differences in damping in the dynamical core strongly influence transient eddy amplitudes. Historical uncertainty in modelled lower stratospheric temperatures persists in APE.Aspects of the circulation generated more directly by interactions between the resolved fluid dynamics and parameterized moist processes vary greatly. The tropical Hadley circulation forms either a single or double inter-tropical convergence zone (ITCZ) at the equator, with large variations in mean precipitation. The equatorial wave spectrum shows a wide range of precipitation intensity and propagation characteristics. Kelvin mode-like eastward propagation with remarkably constant phase speed dominates in most models. Westward propagation, less dispersive than the equatorial Rossby modes, dominates in a few models or occurs within an eastward propagating envelope in others. The mean structure of the ITCZ is related to precipitation variability, consistent with previous studies.The aqua-planet global energy balance is unknown but the models produce a surprisingly large range of top of atmosphere global net flux, dominated by differences in shortwave reflection by clouds. A number of newly developed models, not optimised for Earth climate, contribute to this. Possible reasons for differences in the optimised models are discussed.The aqua-planet configuration is intended as one component of an

  15. Prognostic Significance of Human Apurinic/Apyrimidinic Endonuclease (APE/Ref-1) Expression in Rectal Cancer Treated With Preoperative Radiochemotherapy

    SciTech Connect

    Kim, Jun-Sang; Kim, Jin-Man; Liang, Zhe Long; Jang, Ji Young; Kim, Sup; Huh, Gil Ja; Kim, Ki-Hwan; Cho, Moon-June

    2012-01-01

    Purpose: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+). Methods and Materials: APE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated. Results: APE/Ref-1 was expressed in 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046). Conclusions: APE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse

  16. High Seroprevalence of Enterovirus Infections in Apes and Old World Monkeys

    PubMed Central

    McIntyre, Chloe L.; Imai, Natsuko; Clasper, Lucy; Djoko, Cyrille F.; LeBreton, Matthew; Vermeulen, Marion; Saville, Andrew; Mutapi, Francisca; Tamoufé, Ubald; Kiyang, John; Biblia, Tafon G.; Midzi, Nicholas; Mduluza, Takafira; Pépin, Jacques; Njoum, Richard; Smura, Teemu; Fair, Joseph N.; Wolfe, Nathan D.; Roivainen, Merja; Simmonds, Peter

    2012-01-01

    To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates. PMID:22305156

  17. The distal tibia of Hispanopithecus laietanus: more evidence for mosaic evolution in Miocene apes.

    PubMed

    Tallman, Melissa; Almécija, Sergio; Reber, Samantha L; Alba, David M; Moyà-Solà, Salvador

    2013-05-01

    IPS18800 is a partial skeleton attributed to the fossil great ape Hispanopithecus laietanus, and dated to 9.6 Ma (millions of years ago). Previous studies on the postcranial anatomy of this taxon have shown that it displayed a derived, extant great ape-like orthograde body plan with suspensory adaptations, uniquely coupled with adaptations for above-branch pronograde locomotion. Here, for the first time, we describe and analyze in detail the distal tibia of the IPS18800 skeleton of Hispanopithecus with the aid of three-dimensional geometric morphometrics based on 53 landmarks and semilandmarks collected on a broad sample of extant catarrhines and fossil hominoids. Results of principal components and canonical variate analyses reveal that the distal tibia of Hispanopithecus occupies a unique position in the morphospace, similar in some respects to pronograde monkeys, and in other respects to extant apes. The IPS18800 distal tibia combines adaptations for above branch quadrupedalism, such as a keeled trochlear surface and strong intercollicular groove, with adaptations for vertical climbing, such as an anteroposteriorly flattened shaft, enlarged fibular facet and a tibial stop. These results on the distal tibia agree with those from other anatomical regions, indicating that this taxon displayed a locomotor repertoire unlike any extant ape, combining vertical climbing and clambering with above-branch quadrupedalism.

  18. APE-X (Appropriate Placement in English for a Variable, the Individual Goal of Each Student.)

    ERIC Educational Resources Information Center

    Custer County High School, Miles City, MT.

    APE-X, representing Appropriate Placement in English for X (a variable, the individual goal of each student), is designed to individualize instruction by giving students the material they need at the levels of difficulty most appropriate for them. The entire English curriculum is broken into four and one-half week units in five categories;…

  19. Inferences by exclusion in the great apes: the effect of age and species.

    PubMed

    Call, Josep

    2006-10-01

    This study investigated the ability of chimpanzees, gorillas, orangutans, and bonobos to make inferences by exclusion using the procedure pioneered by Premack and Premack (Cognition 50:347-362, 1994) with chimpanzees. Thirty apes were presented with two different food items (banana vs. grape) on a platform and covered with identical containers. One of the items was removed from the container and placed between the two containers so that subjects could see it. After discarding this item, subjects could select between the two containers. In Experiment 1, apes preferentially selected the container that held the item that the experimenter had not discarded, especially if subjects saw the experimenter remove the item from the container (but without seeing the container empty). Experiment 3 in which the food was removed from one of the containers behind a barrier confirmed these results. In contrast, subjects performed at chance levels when a stimulus (colored plastic chip: Exp. 1; food item: Exp. 2 and Exp. 3) designated the item that had been removed. These results indicated that apes made inferences, not just learned to use a discriminative cue to avoid the empty container. Apes perceived and treated the item discarded by the experimenter as if it were the very one that had been hidden under the container. Results suggested a positive relationship between age and inferential ability independent of memory ability but no species differences.

  20. On aspects of skull form in African apes and orangutans, with implications for hominoid evolution.

    PubMed

    Shea, B T

    1985-11-01

    The study of hominoid phylogeny is currently in a state of controversy and debate due to the discovery of new fossil material and reanalysis of the morphology of extant apes. An important key to the resolution of these debates lies in attaining a fuller understanding of the morphological differences in skull form between the African and Asian great apes. In this paper I have analyzed aspects of facial morphology and internal cranial anatomy in the great apes. Results from this study and previous ones suggest that Pongo is characterized by a marked dorsal deflection of the face relative to the basicranium. Many aspects of circumorbital, midfacial, palatal, and mandibular morphology in Pongo may be related to this airorynchous condition. This hypothesis is supported by Enlow's work on form and pattern in the primate and mammalian skull. The position of the face in known Sivapithecus appears to be similar to that seen in Pongo. Although Pongo may be specialized in its marked degree of airorynchy, it seems likely that an important derived feature linking African apes and hominids is a ventral rotation of the splanchnocranium on the neurocranium. The appearance of marked supraorbital tori and ethmofrontal sinuses are probably correlated developments. Additional implications of this work for debates about hominoid phylogeny are discussed.

  1. Antigenic characterization of type C RNA virus isolates of gibbon apes.

    PubMed Central

    Tronick, S R; Stephenson, J R; Aaronson, S A; Kawakami, T G

    1975-01-01

    Type C RNA viruses initially isolated from a lymphosarcoma of a gibbon ape and from a fibrosarcoma of a woolly monkey are very closely related immunologically. However, recent studies have shown that these viruses are distinguishable in a radioimmunoassay for the 12,000-molecular-weight polypeptide (p12) of the woolly monkey virus. In the present report, an immunoassay has been developed for the p12 polypeptide of the gibbon ape type C virus. This assay is shown to further distinguish the woolly monkey and gibbon ape viruses. In type-specific assays for the p12 polypeptides of these viruses, two new type C viruses isolated from gibbons in a second colony, characterized by high incidence of hemopoietic neoplasia, are immunologically distinguishable from the original gibbon ape virus. The p12 type-specific immunoassays described in the present report may be of importance in studying the natural history of these viruses and their relationship to tumors of primates. PMID:46280

  2. Overcoming Drug Resistant Prostate Cancer with APE1/Ref-1 Blockade

    DTIC Science & Technology

    2015-10-01

    1 (APE1/Ref- 1), survivin 3. OVERALL PROJECT SUMMARY: Summarize the progress during appropriate reporting period (single annual or comprehensive...Objectives, and a summary of Results, Progress and Accomplishments with Discussion. Key methodology used during the reporting period , including a description

  3. Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade

    DTIC Science & Technology

    2015-10-01

    1 (APE1/Ref- 1), survivin 3. OVERALL PROJECT SUMMARY: Summarize the progress during appropriate reporting period (single annual or comprehensive...Objectives, and a summary of Results, Progress and Accomplishments with Discussion. Key methodology used during the reporting period , including a description

  4. Functional adaptations in the forelimb muscles of non-human great apes

    PubMed Central

    Myatt, Julia P; Crompton, Robin H; Payne-Davis, Rachel C; Vereecke, Evie E; Isler, Karin; Savage, Russell; D'Août, Kristiaan; Günther, Michael M; Thorpe, Susannah K S

    2012-01-01

    The maximum capability of a muscle can be estimated from simple measurements of muscle architecture such as muscle belly mass, fascicle length and physiological cross-sectional area. While the hindlimb anatomy of the non-human apes has been studied in some detail, a comparative study of the forelimb architecture across a number of species has never been undertaken. Here we present data from chimpanzees, bonobos, gorillas and an orangutan to ascertain if, and where, there are functional differences relating to their different locomotor repertoires and habitat usage. We employed a combination of analyses including allometric scaling and ancovas to explore the data, as the sample size was relatively small and heterogeneous (specimens of different sizes, ages and sex). Overall, subject to possible unidentified, confounding factors such as age effects, it appears that the non-human great apes in this sample (the largest assembled to date) do not vary greatly across different muscle architecture parameters, even though they perform different locomotor behaviours at different frequencies. Therefore, it currently appears that the time spent performing a particular behaviour does not necessarily impose a dominating selective influence on the soft-tissue portion of the musculoskeletal system; rather, the overall consistency of muscle architectural properties both between and within the Asian and African apes strengthens the case for the hypothesis of a possible ancient shared evolutionary origin for orthogrady under compressive and/or suspensory loading in the great apes. PMID:22034995

  5. The great divides: Ardipithecus ramidus reveals the postcrania of our last common ancestors with African apes.

    PubMed

    Lovejoy, C Owen; Suwa, Gen; Simpson, Scott W; Matternes, Jay H; White, Tim D

    2009-10-02

    Genomic comparisons have established the chimpanzee and bonobo as our closest living relatives. However, the intricacies of gene regulation and expression caution against the use of these extant apes in deducing the anatomical structure of the last common ancestor that we shared with them. Evidence for this structure must therefore be sought from the fossil record. Until now, that record has provided few relevant data because available fossils were too recent or too incomplete. Evidence from Ardipithecus ramidus now suggests that the last common ancestor lacked the hand, foot, pelvic, vertebral, and limb structures and proportions specialized for suspension, vertical climbing, and knuckle-walking among extant African apes. If this hypothesis is correct, each extant African ape genus must have independently acquired these specializations from more generalized ancestors who still practiced careful arboreal climbing and bridging. African apes and hominids acquired advanced orthogrady in parallel. Hominoid spinal invagination is an embryogenetic mechanism that reoriented the shoulder girdle more laterally. It was unaccompanied by substantial lumbar spine abbreviation, an adaptation restricted to vertical climbing and/or suspension. The specialized locomotor anatomies and behaviors of chimpanzees and gorillas therefore constitute poor models for the origin and evolution of human bipedality.

  6. Genetic Differences Between Great Apes and Humans: Implications for Human Evolution

    SciTech Connect

    Varki, Ajit

    2004-03-17

    When considering protein sequences, humans are 99-100% identical to chimpanzees and bonobos, our closest evolutionary relatives. The evolution of humans (and the unique features of our species) from a common ancestor with these great apes involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of the differences. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly in relationship to a family of cell surface molecules called sialic acids. These differences have implications for the human condition, ranging from susceptibility or resistance to microbial pathogens; effects on endogenous receptors in the immune system; potential effects on placental signaling; the expression of oncofetal antigens in cancers; consequences of dietary intake of animal foods; and the development of the mammalian brain. This talk will provide an overview of these and other genetic differences between humans and great apes, with attention to differences potentially relevant to the evolution of humans.

  7. Functional adaptations in the forelimb muscles of non-human great apes.

    PubMed

    Myatt, Julia P; Crompton, Robin H; Payne-Davis, Rachel C; Vereecke, Evie E; Isler, Karin; Savage, Russell; D'Août, Kristiaan; Günther, Michael M; Thorpe, Susannah K S

    2012-01-01

    The maximum capability of a muscle can be estimated from simple measurements of muscle architecture such as muscle belly mass, fascicle length and physiological cross-sectional area. While the hindlimb anatomy of the non-human apes has been studied in some detail, a comparative study of the forelimb architecture across a number of species has never been undertaken. Here we present data from chimpanzees, bonobos, gorillas and an orangutan to ascertain if, and where, there are functional differences relating to their different locomotor repertoires and habitat usage. We employed a combination of analyses including allometric scaling and ancovas to explore the data, as the sample size was relatively small and heterogeneous (specimens of different sizes, ages and sex). Overall, subject to possible unidentified, confounding factors such as age effects, it appears that the non-human great apes in this sample (the largest assembled to date) do not vary greatly across different muscle architecture parameters, even though they perform different locomotor behaviours at different frequencies. Therefore, it currently appears that the time spent performing a particular behaviour does not necessarily impose a dominating selective influence on the soft-tissue portion of the musculoskeletal system; rather, the overall consistency of muscle architectural properties both between and within the Asian and African apes strengthens the case for the hypothesis of a possible ancient shared evolutionary origin for orthogrady under compressive and/or suspensory loading in the great apes. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

  8. The risk of tuberculosis transmission to free-ranging great apes.

    PubMed

    Wolf, Tiffany M; Sreevatsan, Srinand; Travis, Dominic; Mugisha, Lawrence; Singer, Randall S

    2014-01-01

    Pathogen exchange between humans and primates has been facilitated by anthropogenic disturbances, such as changing land use patterns, habitat destruction, and poaching, which decrease population sizes and increase levels of primate-human interaction. As a result, human and domestic animal diseases have become a recognized threat to endangered primate populations. Tuberculosis is a major global human and animal health concern, especially in equatorial Africa where many of the remaining free-living great ape populations exist in proximity with exposed and/or infected human populations and their domestic animals. Increased anthropogenic pressure creates an opportunity for the anthropozoonotic spread of this disease. This review examines current evidence of the risk of tuberculosis transmission to great apes, the benefits and limitations of current detection methods, the impact of current great ape conservation and management strategies on this risk, and the need for an ecosystem health-based approach to mitigating the risks of tuberculosis transmission to great apes. © 2013 Wiley Periodicals, Inc.

  9. Diversity, host switching and evolution of Plasmodium vivax infecting African great apes.

    PubMed

    Prugnolle, Franck; Rougeron, Virginie; Becquart, Pierre; Berry, Antoine; Makanga, Boris; Rahola, Nil; Arnathau, Céline; Ngoubangoye, Barthélémy; Menard, Sandie; Willaume, Eric; Ayala, Francisco J; Fontenille, Didier; Ollomo, Benjamin; Durand, Patrick; Paupy, Christophe; Renaud, François

    2013-05-14

    Plasmodium vivax is considered to be absent from Central and West Africa because of the protective effect of Duffy negativity. However, there are reports of persons returning from these areas infected with this parasite and observations suggesting the existence of transmission. Among the possible explanations for this apparent paradox, the existence of a zoonotic reservoir has been proposed. May great apes be this reservoir? We analyze the mitochondrial and nuclear genetic diversity of P. vivax parasites isolated from great apes in Africa and compare it to parasites isolated from travelers returning from these regions of Africa, as well as to human isolates distributed all over the world. We show that the P. vivax sequences from parasites of great apes form a clade genetically distinct from the parasites circulating in humans. We show that this clade's parasites can be infectious to humans by describing the case of a traveler returning from the Central African Republic infected with one of them. The relationship between this P. vivax clade in great apes and the human isolates is discussed.

  10. Palaeontological evidence for an Oligocene divergence between Old World monkeys and apes.

    PubMed

    Stevens, Nancy J; Seiffert, Erik R; O'Connor, Patrick M; Roberts, Eric M; Schmitz, Mark D; Krause, Cornelia; Gorscak, Eric; Ngasala, Sifa; Hieronymus, Tobin L; Temu, Joseph

    2013-05-30

    Apes and Old World monkeys are prominent components of modern African and Asian ecosystems, yet the earliest phases of their evolutionary history have remained largely undocumented. The absence of crown catarrhine fossils older than ∼20 million years (Myr) has stood in stark contrast to molecular divergence estimates of ∼25-30 Myr for the split between Cercopithecoidea (Old World monkeys) and Hominoidea (apes), implying long ghost lineages for both clades. Here we describe the oldest known fossil 'ape', represented by a partial mandible preserving dental features that place it with 'nyanzapithecine' stem hominoids. Additionally, we report the oldest stem member of the Old World monkey clade, represented by a lower third molar. Both specimens were recovered from a precisely dated 25.2-Myr-old stratum in the Rukwa Rift, a segment of the western branch of the East African Rift in Tanzania. These finds extend the fossil record of apes and Old World monkeys well into the Oligocene epoch of Africa, suggesting a possible link between diversification of crown catarrhines and changes in the African landscape brought about by previously unrecognized tectonic activity in the East African rift system.

  11. The magic cup: great apes and domestic dogs (Canis familiaris) individuate objects according to their properties.

    PubMed

    Bräuer, Juliane; Call, Josep

    2011-08-01

    Despite current interest in dog (Canis familiaris) cognition, very little is known about how dogs represent objects and how they compare with other species, such as the great apes. Therefore, we investigated how dogs and great apes (chimpanzees [Pan troglodytes], bonobos [Pan paniscus], orangutans [Pongo pygmaeus], gorillas [Gorilla gorilla]) individuate objects in a classical violation of expectation paradigm. We used a container (magic cup) with a double bottom that allowed us to change the type of food that subjects had seen being placed in the container. Using a 2 × 2 design, we varied whether subjects received a generally preferred food and whether the food was substituted (surprise trials) or not (baseline trials). Apes showed increased begging and looking behaviors and dogs showed increased smelling behavior. Both species stayed near the experimenter more frequently in the surprise trials compared with baseline trials. Both species reacted to positive (i.e., good food substituted for bad food) and negative (i.e., bad food substituted for good food) surprises. These results suggest that apes and dogs were able to individuate objects according to their properties or type in comparable ways. In addition, we looked for frustration and elation effects, but subjects' behaviors were not influenced by the food they saw and which they received in previous trials. PsycINFO Database Record (c) 2011 APA, all rights reserved.

  12. Fossil hominin shoulders support an African ape-like last common ancestor of humans and chimpanzees.

    PubMed

    Young, Nathan M; Capellini, Terence D; Roach, Neil T; Alemseged, Zeresenay

    2015-09-22

    Reconstructing the behavioral shifts that drove hominin evolution requires knowledge of the timing, magnitude, and direction of anatomical changes over the past ∼6-7 million years. These reconstructions depend on assumptions regarding the morphotype of the Homo-Pan last common ancestor (LCA). However, there is little consensus for the LCA, with proposed models ranging from African ape to orangutan or generalized Miocene ape-like. The ancestral state of the shoulder is of particular interest because it is functionally associated with important behavioral shifts in hominins, such as reduced arboreality, high-speed throwing, and tool use. However, previous morphometric analyses of both living and fossil taxa have yielded contradictory results. Here, we generated a 3D morphospace of ape and human scapular shape to plot evolutionary trajectories, predict ancestral morphologies, and directly test alternative evolutionary hypotheses using the hominin fossil evidence. We show that the most parsimonious model for the evolution of hominin shoulder shape starts with an African ape-like ancestral state. We propose that the shoulder evolved gradually along a single morphocline, achieving modern human-like configuration and function within the genus Homo. These data are consistent with a slow, progressive loss of arboreality and increased tool use throughout human evolution.

  13. Fossil hominin shoulders support an African ape-like last common ancestor of humans and chimpanzees

    PubMed Central

    Young, Nathan M.; Capellini, Terence D.; Roach, Neil T.; Alemseged, Zeresenay

    2015-01-01

    Reconstructing the behavioral shifts that drove hominin evolution requires knowledge of the timing, magnitude, and direction of anatomical changes over the past ∼6–7 million years. These reconstructions depend on assumptions regarding the morphotype of the Homo–Pan last common ancestor (LCA). However, there is little consensus for the LCA, with proposed models ranging from African ape to orangutan or generalized Miocene ape-like. The ancestral state of the shoulder is of particular interest because it is functionally associated with important behavioral shifts in hominins, such as reduced arboreality, high-speed throwing, and tool use. However, previous morphometric analyses of both living and fossil taxa have yielded contradictory results. Here, we generated a 3D morphospace of ape and human scapular shape to plot evolutionary trajectories, predict ancestral morphologies, and directly test alternative evolutionary hypotheses using the hominin fossil evidence. We show that the most parsimonious model for the evolution of hominin shoulder shape starts with an African ape-like ancestral state. We propose that the shoulder evolved gradually along a single morphocline, achieving modern human-like configuration and function within the genus Homo. These data are consistent with a slow, progressive loss of arboreality and increased tool use throughout human evolution. PMID:26351685

  14. Quantifying temporal bone morphology of great apes and humans: an approach using geometric morphometrics

    PubMed Central

    Lockwood, Charles A; Lynch, John M; Kimbel, William H

    2002-01-01

    The hominid temporal bone offers a complex array of morphology that is linked to several different functional systems. Its frequent preservation in the fossil record gives the temporal bone added significance in the study of human evolution, but its morphology has proven difficult to quantify. In this study we use techniques of 3D geometric morphometrics to quantify differences among humans and great apes and discuss the results in a phylogenetic context. Twenty-three landmarks on the ectocranial surface of the temporal bone provide a high level of anatomical detail. Generalized Procrustes analysis (GPA) is used to register (adjust for position, orientation and scale) landmark data from 405 adults representing Homo, Pan, Gorilla and Pongo. Principal components analysis of residuals from the GPA shows that the major source of variation is between humans and apes. Human characteristics such as a coronally orientated petrous axis, a deep mandibular fossa, a projecting mastoid process, and reduced lateral extension of the tympanic element strongly impact the analysis. In phenetic cluster analyses, gorillas and orangutans group together with respect to chimpanzees, and all apes group together with respect to humans. Thus, the analysis contradicts depictions of African apes as a single morphotype. Gorillas and orangutans lack the extensive preglenoid surface of chimpanzees, and their mastoid processes are less medially inflected. These and other characters shared by gorillas and orangutans are probably primitive for the African hominid clade. PMID:12489757

  15. Estimation of the ancestral effective population sizes of African great apes under different selection regimes.

    PubMed

    Schrago, Carlos G

    2014-08-01

    Reliable estimates of ancestral effective population sizes are necessary to unveil the population-level phenomena that shaped the phylogeny and molecular evolution of the African great apes. Although several methods have previously been applied to infer ancestral effective population sizes, an analysis of the influence of the selective regime on the estimates of ancestral demography has not been thoroughly conducted. In this study, three independent data sets under different selective regimes were used were composed to tackle this issue. The results showed that selection had a significant impact on the estimates of ancestral effective population sizes of the African great apes. The inference of the ancestral demography of African great apes was affected by the selection regime. The effects, however, were not homogeneous along the ancestral populations of great apes. The effective population size of the ancestor of humans and chimpanzees was more impacted by the selection regime when compared to the same parameter in the ancestor of humans, chimpanzees and gorillas. Because the selection regime influenced the estimates of ancestral effective population size, it is reasonable to assume that a portion of the discrepancy found in previous studies that inferred the ancestral effective population size may be attributable to the differential action of selection on the genes sampled.

  16. Apes finding ants: Predator-prey dynamics in a chimpanzee habitat in Nigeria.

    PubMed

    Pascual-Garrido, Alejandra; Umaru, Buba; Allon, Oliver; Sommer, Volker

    2013-12-01

    Some chimpanzee populations prey upon army ants, usually with stick tools. However, how their prey's subterranean nesting and nomadic lifestyle influence the apes' harvesting success is still poorly understood. This is particularly true for chimpanzees (Pan troglodytes ellioti) at Gashaka/Nigeria, which consume army ants (Dorylus rubellus) with much higher frequency than at other sites. We assessed various harvesting and search options theoretically available to the apes. For this, we reconstructed annual consumption patterns from feces and compared the physical characteristics of exploited ant nests with those that were not targeted. Repeated exploitation of a discovered nest is viable only in the short term, as disturbed colonies soon moved to a new site. Moreover, monitoring previously occupied nest cavities is uneconomical, as ants hardly ever re-used them. Thus, the apes have to detect new nests regularly, although colony density is relatively low (1 colony/1.3 ha). Surprisingly, visual search cues seem to be of limited importance because the probability of a nest being exploited was independent of its conspicuousness (presence of excavated soil piles, concealing leaf-litter or vegetation). However, chimpanzees preferentially targeted nests in forests or at the base of food trees, that is, where the apes spend relatively more time and/or where ant colony density is highest. Taken together, our findings suggest that, instead of employing a search strategy based on visual cues or spatial memory, chimpanzee predation on army ants contains a considerable opportunistic element.

  17. High seroprevalence of enterovirus infections in apes and old world monkeys.

    PubMed

    Harvala, Heli; McIntyre, Chloe L; Imai, Natsuko; Clasper, Lucy; Djoko, Cyrille F; LeBreton, Matthew; Vermeulen, Marion; Saville, Andrew; Mutapi, Francisca; Tamoufé, Ubald; Kiyang, John; Biblia, Tafon G; Midzi, Nicholas; Mduluza, Takafira; Pépin, Jacques; Njouom, Richard; Njoum, Richard; Smura, Teemu; Fair, Joseph N; Wolfe, Nathan D; Roivainen, Merja; Simmonds, Peter

    2012-02-01

    To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.

  18. Review and hypothesis: does Graves' disease develop in non-human great apes?

    PubMed

    McLachlan, Sandra M; Alpi, Kristine; Rapoport, Basil

    2011-12-01

    Graves' disease, caused by stimulatory thyrotropin receptor (TSHR) autoantibodies, has not been observed in animals. In contrast, Hashimoto's thyroiditis develops in chickens, rats, mice, dogs, and marmosets. Attempts to induce an immune response in mice to the luteinizing-hormone receptor suggested that autoantigen glycosylation was one parameter involved in breaking self-tolerance. Over evolution, TSHR glycosylation increased from three asparagine-linked-glycans (N-glycans) in fish to six N-glycans in humans and great apes. All other placental mammals lack one N-glycan in the shed TSHR A-subunit, the primary Graves' disease autoantigen. We hypothesized that (a) lesser TSHR A-subunit glycosylation reduces immunogenicity, accounting for the absence of Graves' disease in most placental mammals; (b) due to human-like A-subunit glycosylation, Graves' disease might arise in great apes. Here, we review and analyze the literature on this subject and report the results of a survey of veterinarians at primate centers and zoos in North America. Previous experimental data from induced TSHR antibodies in mice support a role for A-subunit glycosylation in breaking self-tolerance. An extensive search of the great-ape literature revealed five reports of noncongenital thyroid dysfunction, four with hypothyroidism and one with hyperthyroidism. The latter was a gorilla who was treated with anti-thyroid drugs but is now deceased. Neither serum nor thyroid tissue from this gorilla were available for analysis. The survey of veterinarians revealed that none of the 979 chimpanzees in primate research centers had a diagnosis of noncongenital thyroid dysfunction and among ∼1100 great apes (gorillas, orangutans, and chimpanzees) in U.S. zoos, only three were hypothyroid, and none were hyperthyroid. Graves' disease appears to be either very rare or does not occur in great apes based on the literature and a survey of veterinarians. Although the available data do not advance our hypothesis

  19. Hematocrit and Hemoglobin Levels of Nonhuman Apes at Moderate Altitudes: A Comparison with Humans.

    PubMed

    Mortola, Jacopo P; Wilfong, DeeAnn

    2016-12-01

    Mortola, Jacopo P. and DeeAnn Wilfong. Hematocrit and hemoglobin levels of nonhuman apes at moderate altitudes: a comparison with humans. High Alt Med Biol. 17:323-335, 2016.-We asked to what extent the hematologic response (increase in hematocrit [Hct] and in blood hemoglobin concentration [Hb]) of humans to altitude hypoxia was shared by our closest relatives, the nonhuman apes. Data were collected from 29 specimens of 7 species of apes at 2073 m altitude (barometric pressure Pb = 598 mm Hg); additional data originated from apes located at a lower altitude (1493 m, Pb = 639 mm Hg). The human altitude profiles of Hct and Hb between sea level and 3000 m were constructed from a compilation of literature sources that (all combined) comprised data sets of 10,000-12,000 subjects for each gender. These human data were binned for 0-250 m altitude (sea level) and for each 500 m of progressively higher altitudes. Values of Hb and Hct of both men and women were significantly higher than at sea level at the 1500 bin (1250-1750 m); hence, the altitude threshold for the human hematological responses must be between 1000 and 1500 m. In the nonhuman apes, no increase in Hct or Hb was apparent at 1500 m; at 2000 m, the increase was significant only for the Hb of females. At either altitude in the group of nonhuman apes, the increase in Hct was much less than in humans, and that of Hb was significantly less at 1500 m. We conclude that lack of, or minimal, hematopoietic response to moderate altitude can occur in mammalian species that are not genetically adapted to high altitudes. Polycythemia is not a common response to altitude hypoxia and, at least at moderate altitudes, the degree of the human response may represent the exception among apes rather than the rule.

  20. Review and Hypothesis: Does Graves' Disease Develop in Non-Human Great Apes?

    PubMed Central

    Alpi, Kristine; Rapoport, Basil

    2011-01-01

    Background Graves' disease, caused by stimulatory thyrotropin receptor (TSHR) autoantibodies, has not been observed in animals. In contrast, Hashimoto's thyroiditis develops in chickens, rats, mice, dogs, and marmosets. Attempts to induce an immune response in mice to the luteinizing-hormone receptor suggested that autoantigen glycosylation was one parameter involved in breaking self-tolerance. Over evolution, TSHR glycosylation increased from three asparagine-linked-glycans (N-glycans) in fish to six N-glycans in humans and great apes. All other placental mammals lack one N-glycan in the shed TSHR A-subunit, the primary Graves' disease autoantigen. We hypothesized that (a) lesser TSHR A-subunit glycosylation reduces immunogenicity, accounting for the absence of Graves' disease in most placental mammals; (b) due to human-like A-subunit glycosylation, Graves' disease might arise in great apes. Here, we review and analyze the literature on this subject and report the results of a survey of veterinarians at primate centers and zoos in North America. Summary Previous experimental data from induced TSHR antibodies in mice support a role for A-subunit glycosylation in breaking self-tolerance. An extensive search of the great-ape literature revealed five reports of noncongenital thyroid dysfunction, four with hypothyroidism and one with hyperthyroidism. The latter was a gorilla who was treated with anti-thyroid drugs but is now deceased. Neither serum nor thyroid tissue from this gorilla were available for analysis. The survey of veterinarians revealed that none of the 979 chimpanzees in primate research centers had a diagnosis of noncongenital thyroid dysfunction and among ∼1100 great apes (gorillas, orangutans, and chimpanzees) in U.S. zoos, only three were hypothyroid, and none were hyperthyroid. Conclusions Graves' disease appears to be either very rare or does not occur in great apes based on the literature and a survey of veterinarians. Although the available data

  1. Problem solving in great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, and Pongo abelii): the effect of visual feedback.

    PubMed

    Völter, Christoph J; Call, Josep

    2012-09-01

    What kind of information animals use when solving problems is a controversial topic. Previous research suggests that, in some situations, great apes prefer to use causally relevant cues over arbitrary ones. To further examine to what extent great apes are able to use information about causal relations, we presented three different puzzle box problems to the four nonhuman great ape species. Of primary interest here was a comparison between one group of apes that received visual access to the functional mechanisms of the puzzle boxes and one group that did not. Apes' performance in the first two, less complex puzzle boxes revealed that they are able to solve such problems by means of trial-and-error learning, requiring no information about the causal structure of the problem. However, visual inspection of the functional mechanisms of the puzzle boxes reduced the amount of time needed to solve the problems. In the case of the most complex problem, which required the use of a crank, visual feedback about what happened when the handle of the crank was turned was necessary for the apes to solve the task. Once the solution was acquired, however, visual feedback was no longer required. We conclude that visual feedback about the consequences of their actions helps great apes to solve complex problems. As the crank task matches the basic requirements of vertical string pulling in birds, the present results are discussed in light of recent findings with corvids.

  2. Rapid Categorization of Human and Ape Faces in 9-Month-Old Infants Revealed by Fast Periodic Visual Stimulation.

    PubMed

    Peykarjou, Stefanie; Hoehl, Stefanie; Pauen, Sabina; Rossion, Bruno

    2017-10-02

    This study investigates categorization of human and ape faces in 9-month-olds using a Fast Periodic Visual Stimulation (FPVS) paradigm while measuring EEG. Categorization responses are elicited only if infants discriminate between different categories and generalize across exemplars within each category. In study 1, human or ape faces were presented as standard and deviant stimuli in upright and inverted trials. Upright ape faces presented among humans elicited strong categorization responses, whereas responses for upright human faces and for inverted ape faces were smaller. Deviant inverted human faces did not elicit categorization. Data were best explained by a model with main effects of species and orientation. However, variance of low-level image characteristics was higher for the ape than the human category. Variance was matched to replicate this finding in an independent sample (study 2). Both human and ape faces elicited categorization in upright and inverted conditions, but upright ape faces elicited the strongest responses. Again, data were best explained by a model of two main effects. These experiments demonstrate that 9-month-olds rapidly categorize faces, and unfamiliar faces presented among human faces elicit increased categorization responses. This likely reflects habituation for the familiar standard category, and stronger release for the unfamiliar category deviants.

  3. APE1 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis.

    PubMed

    Yuan, Chun-Ling; He, Fan; Ye, Jia-Zhou; Wu, Hui-Ni; Zhang, Jin-Yan; Liu, Zhi-Hui; Li, Yong-Qiang; Luo, Xiao-Ling; Lin, Yan; Liang, Rong

    2017-08-29

    APE1 is known as a key mediator of DNA damage repair pathways, and its clinical significance in different types of cancer is well studied. Herein, we performed a meta-analysis to determine the association of APE1 expression and survival in different types of solid cancer. We searched all eligible publications in PubMed, Web of Science and Embase platforms from inception to January 2017 and found 15 relevant manuscripts. Overall survival (OS), 12- and 36-month survival rates, and hazard ratios (HRs) were extracted and analyzed. Heterogeneity and publication bias were also assessed. A subgroup analysis of the different subcellular locations of APE1 was also conducted. Patients with higher APE1 levels demonstrated lower 12- and 36-month survival rates than those with low APE1 levels (HR 2.00, 95% CI 1.33-3.00, P = 0.0009; HR 1.84, 95% CI 1.19-2.84, P = 0.006). Importantly, the pooled analysis showed that high levels of APE1 predict shorter OS (HR 1.44, 95% CI 1.13-1.83, P = 0.003). Subgroup analysis revealed that both nuclear and cytoplasmic expression levels of APE1 are important indicators of poor prognosis in solid tumors.

  4. Comparing ape densities and habitats in northern Congo: surveys of sympatric gorillas and chimpanzees in the Odzala and Ndoki regions.

    PubMed

    Devos, Céline; Sanz, Crickette; Morgan, David; Onononga, Jean-Robert; Laporte, Nadine; Huynen, Marie-Claude

    2008-05-01

    The conservation status of western lowland gorillas and central chimpanzees in western equatorial Africa remains largely speculative because many remote areas have never been surveyed and the impact of emergent diseases in the region has not been well documented. In this study, we compared ape densities and habitats in the Lokoué study area in Odzala National Park and the Goualougo Triangle in Nouabalé-Ndoki National Park in northern Republic of Congo. Both of these sites have long been considered strongholds for the conservation of chimpanzees and gorillas, but supposedly differ in vegetative composition and relative ape abundance. We compared habitats between these sites using conventional ground surveys and classified Landsat-7 ETM+ satellite images. We present density estimates via both standing-crop and marked-nest methods for the first time for sympatric apes of the Congo Basin. The marked-nest method was effective in depicting chimpanzee densities, but underestimated gorilla densities at both sites. Marked-nest surveys also revealed a dramatic decline in the ape population of Lokoué which coincided with a local Ebola epidemic. Normal baseline fluctuations in ape nest encounter rates during the repeated passages of marked-nest surveys were clearly distinguishable from a 80% decline in ape nest encounter rates at Lokoué. Our results showed that ape densities, habitat composition, and population dynamics differed between these populations in northern Congo. We emphasize the importance of intensifying monitoring efforts and further refinement of ape survey methods, as our results indicated that even the largest remaining ape populations in intact and protected forests are susceptible to sudden and dramatic declines.

  5. Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

    PubMed Central

    Dai, Nan; Guan, Wei; Shan, Jinlu; Yang, Xueqin; Zhong, Zhaoyang; Qing, Yi; Jin, Feng; Chen, Chuan; Yang, Yuxin; Wang, Hongyi; Baugh, Laura; Tell, Gianluca; Wilson, David M.; Li, Mengxia; Wang, Dong

    2016-01-01

    Purpose To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy. Results Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010). Experimental Design We measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control. Conclusions Our studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-naïve serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival. PMID:27813497

  6. Ontogenetic variation in the mandibular ramus of great apes and humans.

    PubMed

    Terhune, Claire E; Robinson, Chris A; Ritzman, Terrence B

    2014-06-01

    Considerable variation exists in mandibular ramus form among primates, particularly great apes and humans. Recent analyses of adult ramal morphology have suggested that features on the ramus, especially the coronoid process and sigmoid notch, can be treated as phylogenetic characters that can be used to reconstruct relationships among great ape and fossil hominin taxa. Others have contended that ramal morphology is more influenced by function than phylogeny. In addition, it remains unclear how ontogeny of the ramus contributes to adult variation in great apes and humans. Specifically, it is unclear whether differences among adults appear early and are maintained throughout ontogeny, or if these differences appear, or are enhanced, during later development. To address these questions, the present study examined a broad ontogenetic sample of great apes and humans using two-dimensional geometric morphometric analysis. Variation within and among species was summarized using principal component and thin plate spline analyses, and Procrustes distances and discriminant function analyses were used to statistically compare species and age classes. Results suggest that morphological differences among species in ramal morphology appear early in ontogeny and persist into adulthood. Morphological differences among adults are particularly pronounced in the height and angulation of the coronoid process, the depth and anteroposterior length of the sigmoid notch, and the inclination of the ramus. In all taxa, the ascending ramus of the youngest specimens is more posteriorly inclined in relation to the occlusal plane, shifting to become more upright in adults. These results suggest that, although there are likely functional influences over the form of the coronoid process and ramus, the morphology of this region can be profitably used to differentiate among great apes, modern humans, and fossil hominid taxa. Copyright © 2014 Wiley Periodicals, Inc.

  7. What’s Special about Human Imitation? A Comparison with Enculturated Apes

    PubMed Central

    Subiaul, Francys

    2016-01-01

    What, if anything, is special about human imitation? An evaluation of enculturated apes’ imitation skills, a “best case scenario” of non-human apes’ imitation performance, reveals important similarities and differences between this special population of apes and human children. Candidates for shared imitation mechanisms include the ability to imitate various familiar transitive responses and object–object actions that involve familiar tools. Candidates for uniquely derived imitation mechanisms include: imitating novel transitive actions and novel tool-using responses as well as imitating opaque or intransitive gestures, regardless of familiarity. While the evidence demonstrates that enculturated apes outperform non-enculturated apes and perform more like human children, all apes, regardless of rearing history, generally excel at imitating familiar, over-rehearsed responses and are poor, relative to human children, at imitating novel, opaque or intransitive responses. Given the similarities between the sensory and motor systems of preschool age human children and non-human apes, it is unlikely that differences in sensory input and/or motor-output alone explain the observed discontinuities in imitation performance. The special rearing history of enculturated apes—including imitation-specific training—further diminishes arguments suggesting that differences are experience-dependent. Here, it is argued that such differences are best explained by distinct, specialized mechanisms that have evolved for copying rules and responses in particular content domains. Uniquely derived social and imitation learning mechanisms may represent adaptations for learning novel communicative gestures and complex tool-use. Given our species’ dependence on both language and tools, mechanisms that accelerated learning in these domains are likely to have faced intense selective pressures, starting with the earliest of human ancestors. PMID:27399786

  8. Patterns of differences in brain morphology in humans as compared to extant apes

    PubMed Central

    Aldridge, Kristina

    2010-01-01

    Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. PMID:21056456

  9. Cloning and Characterization of a Wheat Homologue of Apurinic/Apyrimidinic Endonuclease Ape1L

    PubMed Central

    Grin, Inga R.; Zharkov, Dmitry O.; Ishenko, Alexander A.; Tudek, Barbara; Bissenbaev, Amangeldy K.; Saparbaev, Murat

    2014-01-01

    Background Apurinic/apyrimidinic (AP) endonucleases are key DNA repair enzymes involved in the base excision repair (BER) pathway. In BER, an AP endonuclease cleaves DNA at AP sites and 3′-blocking moieties generated by DNA glycosylases and/or oxidative damage. A Triticum aestivum cDNA encoding for a putative homologue of ExoIII family AP endonucleases which includes E. coli Xth, human APE1 and Arabidopsis thaliana AtApe1L has been isolated and its protein product purified and characterized. Methodology/Principal Findings We report that the putative wheat AP endonuclease, referred here as TaApe1L, contains AP endonuclease, 3′-repair phosphodiesterase, 3′-phosphatase and 3′→5′ exonuclease activities. Surprisingly, in contrast to bacterial and human AP endonucleases, addition of Mg2+ and Ca2+ (5–10 mM) to the reaction mixture inhibited TaApe1L whereas the presence of Mn2+, Co2+ and Fe2+ cations (0.1–1.0 mM) strongly stimulated all its DNA repair activities. Optimization of the reaction conditions revealed that the wheat enzyme requires low divalent cation concentration (0.1 mM), mildly acidic pH (6–7), low ionic strength (20 mM KCl) and has a temperature optimum at around 20°C. The steady-state kinetic parameters of enzymatic reactions indicate that TaApe1L removes 3′-blocking sugar-phosphate and 3′-phosphate groups with good efficiency (kcat/KM = 630 and 485 μM−1·min−1, respectively) but possesses a very weak AP endonuclease activity as compared to the human homologue, APE1. Conclusions/Significance Taken together, these data establish the DNA substrate specificity of the wheat AP endonuclease and suggest its possible role in the repair of DNA damage generated by endogenous and environmental factors. PMID:24667595

  10. Ape1/Ref-1 Induces Glial Cell-Derived Neurotropic Factor (GDNF) Responsiveness by Upregulating GDNF Receptor α1 Expression ▿ ‡

    PubMed Central

    Kim, Mi-Hwa; Kim, Hong-Beum; Acharya, Samudra; Sohn, Hong-Moon; Jun, Jae Yeoul; Chang, In-Youb; You, Ho Jin

    2009-01-01

    Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) dysregulation has been identified in several human tumors and in patients with a variety of neurodegenerative diseases. However, the function of Ape1/Ref-1 is unclear. We show here that Ape1/Ref-1 increases the expression of glial cell-derived neurotropic factor (GDNF) receptor α1 (GFRα1), a key receptor for GDNF. Expression of Ape1/Ref-1 led to an increase in the GDNF responsiveness in human fibroblast. Ape1/Ref-1 induced GFRα1 transcription through enhanced binding of NF-κB complexes to the GFRα1 promoter. GFRα1 levels correlate proportionally with Ape1/Ref-1 in cancer cells. The knockdown of endogenous Ape1/Ref-1 in pancreatic cancer cells markedly suppressed GFRα1 expression and invasion in response to GNDF, while overexpression of GFRα1 restored invasion. In neuronal cells, the Ape1/Ref-1-mediated increase in GDNF responsiveness not only stimulated neurite outgrowth but also protected the cells from β-amyloid peptide and oxidative stress. Our results show that Ape1/Ref-1 is a novel physiological regulator of GDNF responsiveness, and they also suggest that Ape1/Ref-1-induced GFRα1 expression may play important roles in pancreatic cancer progression and neuronal cell survival. PMID:19188437

  11. SY 17-1 DYNAMIC REGULATION OF REDOX REGULATING FACTOR APE1/REF-1 ON THE OXIDATIVE STRESS AND VASCULAR INFLAMMATION.

    PubMed

    Jeon, Byeong Hwa

    2016-09-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 is essential for cellular survival and embryonic lethal in knockout mouse models. Heterozygous APE1/Ref-1 mice showed impaired endothelium-dependent vasorelaxation, reduced vascular NO levels, and are hypertensive. APE1/Ref-1 reduces intracellular reactive oxygen species production by negatively regulating the activity of the NADPH oxidase. APE1/Ref-1 is predominantly localized in the nucleus; however, its subcellular localization is dynamically regulated. Recently, it was shown that APE1/Ref-1 is secreted in response to hyperacetylation at specific lysine residues. We investigated the functions of extracellular APE1/Ref-1 with respect to leading anti-inflammatory signaling in TNF-α-stimulated endothelial cells in response to acetylation. Trichostatin A (TSA), an inhibitor of histone deacetylase, considerably suppressed vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-stimulated endothelial cells. During TSA-mediated acetylation in culture, a time-dependent increase in secreted APE1/Ref-1 was confirmed. Recombinant human APE1/Ref-1 with reducing activity induced a conformational change in TNFR1 by thiol-disulfide exchange. Following treatment with the neutralizing anti-APE1/Ref-1 antibody, inflammatory signals via the binding of TNF-α to TNFR1 were remarkably recovered. Furthermore, rhAPE1/Ref-1 inhibited IL-1β-induced VCAM-1 expression in endothelial cells, and it inhibited iNOS or COX-2 expression in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. These results strongly indicate that anti-inflammatory effects of secreted APE1/Ref-1 and its property of secreted APE1/Ref-1 may be useful as a therapeutic biomolecule in cardiovascular disease.

  12. Nuclear depletion of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is an indicator of energy disruption in neurons.

    PubMed

    Singh, Shilpee; Englander, Ella W

    2012-11-01

    Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is a multifunctional protein critical for cellular survival. Its involvement in adaptive survival responses includes key roles in redox sensing, transcriptional regulation, and repair of DNA damage via the base excision repair (BER) pathway. Ape1 is abundant in most cell types and central in integrating the first BER step catalyzed by different DNA glycosylases. BER is the main process for removal of oxidative DNA lesions in postmitotic brain cells, and after ischemic brain injury preservation of Ape1 coincides with neuronal survival, while its loss has been associated with neuronal death. Here, we report that in cultured primary neurons, diminution of cellular ATP by either oligomycin or H(2)O(2) is accompanied by depletion of nuclear Ape1, while other BER proteins are unaffected and retain their nuclear localization under these conditions. Importantly, while H(2)O(2) induces γH2AX phosphorylation, indicative of chromatin rearrangements in response to DNA damage, oligomycin does not. Furthermore, despite comparable diminution of ATP content, H(2)O(2) and oligomycin differentially affect critical parameters of mitochondrial respiration that ultimately determine cellular ATP content. Taken together, our findings demonstrate that in neurons, nuclear compartmentalization of Ape1 depends on ATP and loss of nuclear Ape1 reflects disruption of neuronal energy homeostasis. Energy crisis is a hallmark of stroke and other ischemic/hypoxic brain injuries. In vivo studies have shown that Ape1 deficit precedes neuronal loss in injured brain regions. Thus, our findings bring to light the possibility that energy failure-induced Ape1 depletion triggers neuronal death in ischemic brain injuries.

  13. The repair function of the multifunctional DNA repair/redox protein APE1 is neuroprotective after ionizing radiation.

    PubMed

    Vasko, Michael R; Guo, Chunlu; Thompson, Eric L; Kelley, Mark R

    2011-09-05

    Although exposure to ionizing radiation (IR) can produce significant neurotoxicity, the mechanisms mediating this toxicity remain to be determined. Previous studies using neurons isolated from the central nervous system show that IR produces reactive oxygen species and oxidative DNA damage in those cells. Because the base excision DNA repair pathway repairs single-base modifications caused by ROS, we asked whether manipulating this pathway by altering APE1 expression would affect radiation-induced neurotoxicity. In cultures of adult hippocampal and sensory neurons, IR produces DNA damage as measured by phosphorylation of histone H2A.X and results in dose-dependent cell death. In isolated sensory neurons, we demonstrate for the first time that radiation decreases the capsaicin-evoked release of the neuropeptide CGRP. Reducing APE1 expression in cultured cells augments IR-induced neurotoxicity, whereas overexpressing APE1 is neuroprotective. Using lentiviral constructs with a neuronal specific promoter that selectively expresses APE1s different functions in neurons, we show that selective expression of the DNA repair competent (redox inactive) APE1 constructs in sensory neurons resurrects cell survival and neuronal function, whereas use of DNA-repair deficient (redox active) constructs is not protective. Use of an APE1 redox-specific inhibitor, APX3330, also facilitates neuronal protection against IR-induced toxicity. These results demonstrate for the first time that the repair function of APE1 is required to protect both hippocampal and DRG neuronal cultures--specifically neuronal cells--from IR-induced damage, while the redox activity of APE1 does not appear to be involved. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. The repair function of the multifunctional DNA repair/redox protein APE1 is neuroprotective after ionizing radiation

    PubMed Central

    Vasko, Michael R.; Guo, Chunlu; Thompson, Eric L.; Kelley, Mark R.

    2011-01-01

    Although exposure to ionizing radiation (IR) can produce significant neurotoxicity, the mechanisms mediating this toxicity remain to be determined. Previous studies using neurons isolated from the central nervous system show that IR produces reactive oxygen species and oxidative DNA damage in those cells. Because the base excision DNA repair pathway repairs single-base modifications caused by ROS, we asked whether manipulating this pathway by altering APE1 expression would affect radiation-induced neurotoxicity. In cultures of adult hippocampal and sensory neurons, IR produces DNA damage as measured by phosphorylation of histone H2A.X and results in dose-dependent cell death. In isolated sensory neurons, we demonstrate for the first time that radiation decreases the capsaicin-evoked release of the neuropeptide CGRP. Reducing APE1 expression in cultured cells augments IR-induced neurotoxicity, whereas overexpressing APE1 is neuroprotective. Using lentiviral constructs with a neuronal specific promoter that selectively expresses APE1’s different functions in neurons, we show that selective expression of the DNA repair competent (redox inactive) APE1 constructs in sensory neurons resurrects cell survival and neuronal function, whereas use of DNA-repair deficient (redox active) constructs is not protective. Use of an APE1 redox-specific inhibitor, APX3330, also facilitates neuronal protection against IR-induced toxicity. These results demonstrate for the first time that the repair function of APE1 is required to protect both hippocampal and DRG neuronal cultures—specifically neuronal cells—from IR-induced damage, while the redox activity of APE1 does not appear to be involved. PMID:21741887

  15. Mitochondrial genes support a common origin of rodent malaria parasites and Plasmodium falciparum's relatives infecting great apes.

    PubMed

    Blanquart, Samuel; Gascuel, Olivier

    2011-03-15

    Plasmodium falciparum is responsible for the most acute form of human malaria. Most recent studies demonstrate that it belongs to a monophyletic lineage specialized in the infection of great ape hosts. Several other Plasmodium species cause human malaria. They all belong to another distinct lineage of parasites which infect a wider range of primate species. All known mammalian malaria parasites appear to be monophyletic. Their clade includes the two previous distinct lineages of parasites of primates and great apes, one lineage of rodent parasites, and presumably Hepatocystis species. Plasmodium falciparum and great ape parasites are commonly thought to be the sister-group of all other mammal-infecting malaria parasites. However, some studies supported contradictory origins and found parasites of great apes to be closer to those of rodents, or to those of other primates. To distinguish between these mutually exclusive hypotheses on the origin of Plasmodium falciparum and its great ape infecting relatives, we performed a comprehensive phylogenetic analysis based on a data set of three mitochondrial genes from 33 to 84 malaria parasites. We showed that malarial mitochondrial genes have evolved slowly and are compositionally homogeneous. We estimated their phylogenetic relationships using Bayesian and maximum-likelihood methods. Inferred trees were checked for their robustness to the (i) site selection, (ii) assumptions of various probabilistic models, and (iii) taxon sampling. Our results robustly support a common ancestry of rodent parasites and Plasmodium falciparum's relatives infecting great apes. Our results refute the most common view of the origin of great ape malaria parasites, and instead demonstrate the robustness of a less well-established phylogenetic hypothesis, under which Plasmodium falciparum and its relatives infecting great apes are closely related to rodent parasites. This study sheds light on the evolutionary history of Plasmodium falciparum, a

  16. Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions.

    PubMed

    Fantini, Damiano; Vascotto, Carlo; Marasco, Daniela; D'Ambrosio, Chiara; Romanello, Milena; Vitagliano, Luigi; Pedone, Carlo; Poletto, Mattia; Cesaratto, Laura; Quadrifoglio, Franco; Scaloni, Andrea; Radicella, J Pablo; Tell, Gianluca

    2010-12-01

    Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is involved in base excision DNA repair (BER) and in regulation of gene expression, acting as a redox co-activator of several transcription factors. Recent findings highlight a novel role for APE1 in RNA metabolism, which is modulated by nucleophosmin (NPM1). The results reported in this article show that five lysine residues (K24, K25, K27, K31 and K32), located in the APE1 N-terminal unstructured domain, are involved in the interaction of APE1 with both RNA and NPM1, thus supporting a competitive binding mechanism. Data from kinetic experiments demonstrate that the APE1 N-terminal domain also serves as a device for fine regulation of protein catalytic activity on abasic DNA. Interestingly, some of these critical lysine residues undergo acetylation in vivo. These results suggest that protein-protein interactions and/or post-translational modifications involving APE1 N-terminal domain may play important in vivo roles, in better coordinating and fine-tuning protein BER activity and function on RNA metabolism.

  17. APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination.

    PubMed

    Xu, Jianliang; Husain, Afzal; Hu, Wenjun; Honjo, Tasuku; Kobayashi, Maki

    2014-12-02

    Activation-induced cytidine deaminase (AID) is essential for antibody diversification, namely somatic hypermutation (SHM) and class switch recombination (CSR). The deficiency of apurinic/apyrimidinic endonuclease 1 (Ape1) in CH12F3-2A B cells reduces CSR to ∼20% of wild-type cells, whereas the effect of APE1 loss on SHM has not been examined. Here we show that, although APE1's endonuclease activity is important for CSR, it is dispensable for SHM as well as IgH/c-myc translocation. Importantly, APE1 deficiency did not show any defect in AID-induced S-region break formation, but blocked both the recruitment of repair protein Ku80 to the S region and the synapse formation between Sμ and Sα. Knockdown of end-processing factors such as meiotic recombination 11 homolog (MRE11) and carboxy-terminal binding protein (CtBP)-interacting protein (CtIP) further reduced the remaining CSR in Ape1-null CH12F3-2A cells. Together, our results show that APE1 is dispensable for SHM and AID-induced DNA breaks and may function as a DNA end-processing enzyme to facilitate the joining of broken ends during CSR.

  18. APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination

    PubMed Central

    Xu, Jianliang; Husain, Afzal; Hu, Wenjun; Honjo, Tasuku; Kobayashi, Maki

    2014-01-01

    Activation-induced cytidine deaminase (AID) is essential for antibody diversification, namely somatic hypermutation (SHM) and class switch recombination (CSR). The deficiency of apurinic/apyrimidinic endonuclease 1 (Ape1) in CH12F3-2A B cells reduces CSR to ∼20% of wild-type cells, whereas the effect of APE1 loss on SHM has not been examined. Here we show that, although APE1’s endonuclease activity is important for CSR, it is dispensable for SHM as well as IgH/c-myc translocation. Importantly, APE1 deficiency did not show any defect in AID-induced S-region break formation, but blocked both the recruitment of repair protein Ku80 to the S region and the synapse formation between Sμ and Sα. Knockdown of end-processing factors such as meiotic recombination 11 homolog (MRE11) and carboxy-terminal binding protein (CtBP)-interacting protein (CtIP) further reduced the remaining CSR in Ape1-null CH12F3-2A cells. Together, our results show that APE1 is dispensable for SHM and AID-induced DNA breaks and may function as a DNA end-processing enzyme to facilitate the joining of broken ends during CSR. PMID:25404348

  19. Anopheles moucheti and Anopheles vinckei are candidate vectors of ape Plasmodium parasites, including Plasmodium praefalciparum in Gabon.

    PubMed

    Paupy, Christophe; Makanga, Boris; Ollomo, Benjamin; Rahola, Nil; Durand, Patrick; Magnus, Julie; Willaume, Eric; Renaud, François; Fontenille, Didier; Prugnolle, Franck

    2013-01-01

    During the last four years, knowledge about the diversity of Plasmodium species in African great apes has considerably increased. Several new species were described in chimpanzees and gorillas, and some species that were previously considered as strictly of human interest were found to be infecting African apes. The description in gorillas of P. praefalciparum, the closest relative of P. falciparum which is the main malignant agent of human malaria, definitively changed the way we understand the evolution and origin of P. falciparum. This parasite is now considered to have appeared recently, following a cross-species transfer from gorillas to humans. However, the Plasmodium vector mosquito species that have served as bridge between these two host species remain unknown. In order to identify the vectors that ensure ape Plasmodium transmission and evaluate the risk of transfer of these parasites to humans, we carried out a field study in Gabon to capture Anopheles in areas where wild and semi-wild ape populations live. We collected 1070 Anopheles females belonging to 15 species, among which An. carnevalei, An. moucheti and An. marshallii were the most common species. Using mtDNA-based PCR tools, we discovered that An. moucheti, a major human malaria vector in Central Africa, could also ensure the natural transmission of P. praefalciparum among great apes. We also showed that, together with An. vinckei, An. moucheti was infected with P. vivax-like parasites. An. moucheti constitutes, therefore, a major candidate for the transfer of Plasmodium parasites from apes to humans.

  20. European Miocene hominids and the origin of the African ape and human clade.

    PubMed

    Begun, David R; Nargolwalla, Mariam C; Kordos, László

    2012-01-01

    In 1871, Darwin famously opined, "In each great region of the world the living mammals are closely related to the extinct species of the same region. It is therefore probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man's nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere." Although this quote is frequently recalled today, Darwin's next line is rarely acknowledged: "But it is useless to speculate on this subject, for an ape nearly as large as a man, namely the Dryopithecus of Lartet, which was closely allied to the anthropomorphous Hylobates, existed in Europe during the Upper Miocene period; and since so remote a period the earth has certainly undergone many great revolutions, and there has been ample time for migration on the largest scale." Copyright © 2012 Wiley Periodicals, Inc.

  1. Great apes use landmark cues over spatial relations to find hidden food.

    PubMed

    Hribar, Alenka; Call, Josep

    2011-09-01

    We investigated whether chimpanzees, bonobos, and orangutans encoded the location of a reward hidden underneath one of three identical cups in relation to (1) the other cups in the array-i.e., the relative position of the baited cup within the array; or (2) the landmarks surrounding the cups-e.g., the edge of the table. Apes witnessed the hiding of a food reward under one of three cups forming a straight line on a platform. After 30 s, they were allowed to search for the reward. In three different experiments, we varied the distance of the cups to the edge of the platform and the distance between the cups. Results showed that both manipulated variables affected apes' retrieval accuracy. Subjects' retrieval accuracy was higher for the outer cups compared with the Middle cup, especially if the outer cups were located next to the platform's edge. Additionally, the larger the distance between the cups, the better performance became.

  2. Memory processing in great apes: the effect of time and sleep.

    PubMed

    Martin-Ordas, Gema; Call, Josep

    2011-12-23

    Following encoding, memory remains temporarily vulnerable to disruption. Consolidation refers to offline time-dependent processes that continue after encoding and stabilize, transform or enhance the memory trace. Memory consolidation resulting from sleep has been reported for declarative and non-declarative memories in humans. We first investigated the temporal course of memory retrieval in chimpanzees, bonobos and orangutans. We found that the amount of retrieved information was time dependent: apes' performance degraded after 1 and 2 h, stabilized after 4 h, started to increase after 8 and 12 h and fully recovered after 24 h. Second, we show that although memories during wakefulness were highly vulnerable to interference from events similar to those witnessed during the original encoding event, an intervening period of sleep not only stabilized apes' memories into more permanent ones but also protected them against interference.

  3. A plethora of Plasmodium species in wild apes: a source of human infection?

    PubMed Central

    Rayner, Julian C.; Liu, Weimin; Peeters, Martine; Sharp, Paul M.; Hahn, Beatrice H.

    2011-01-01

    Recent studies of captive and wild-living apes in Africa have uncovered evidence of numerous new Plasmodium species, one of which was identified as the immediate precursor of human Plasmodium falciparum. These findings raise the question whether wild apes could be a recurrent source of Plasmodium infections in humans. This question is not new, but was the subject of intense investigation by researchers in the first half of the last century. Re-examination of their work in the context of recent molecular findings provides a new framework to understand the diversity of Plasmodium species and to assess the risk of future cross-species transmissions to humans in the context of proposed malaria eradication programs. PMID:21354860

  4. Memory processing in great apes: the effect of time and sleep

    PubMed Central

    Martin-Ordas, Gema; Call, Josep

    2011-01-01

    Following encoding, memory remains temporarily vulnerable to disruption. Consolidation refers to offline time-dependent processes that continue after encoding and stabilize, transform or enhance the memory trace. Memory consolidation resulting from sleep has been reported for declarative and non-declarative memories in humans. We first investigated the temporal course of memory retrieval in chimpanzees, bonobos and orangutans. We found that the amount of retrieved information was time dependent: apes' performance degraded after 1 and 2 h, stabilized after 4 h, started to increase after 8 and 12 h and fully recovered after 24 h. Second, we show that although memories during wakefulness were highly vulnerable to interference from events similar to those witnessed during the original encoding event, an intervening period of sleep not only stabilized apes' memories into more permanent ones but also protected them against interference. PMID:21632621

  5. Detection of Termites and Other Insects Consumed by African Great Apes using Molecular Fecal Analysis

    PubMed Central

    Hamad, Ibrahim; Delaporte, Eric; Raoult, Didier; Bittar, Fadi

    2014-01-01

    The consumption of insects by apes has previously been reported based on direct observations and/or trail signs in feces. However, DNA-based diet analyses may have the potential to reveal trophic links for these wild species. Herein, we analyzed the insect-diet diversity of 9 feces obtained from three species of African great apes, gorilla (Gorilla gorilla gorilla), chimpanzee (Pan troglodytes) and bonobo (Pan paniscus), using two mitochondrial amplifications for arthropods. A total of 1056 clones were sequenced for Cyt-b and COI gene libraries, which contained 50 and 56 operational taxonomic units (OTUs), respectively. BLAST research revealed that the OTUs belonged to 32 families from 5 orders (Diptera, Isoptera, Lepidoptera, Coleoptera, and Orthoptera). While ants were not detected by this method, the consumption of flies, beetles, moths, mosquitoes and termites was evident in these samples. Our findings indicate that molecular techniques can be used to analyze insect food items in wild animals. PMID:24675424

  6. Detection of termites and other insects consumed by African great apes using molecular fecal analysis.

    PubMed

    Hamad, Ibrahim; Delaporte, Eric; Raoult, Didier; Bittar, Fadi

    2014-03-27

    The consumption of insects by apes has previously been reported based on direct observations and/or trail signs in feces. However, DNA-based diet analyses may have the potential to reveal trophic links for these wild species. Herein, we analyzed the insect-diet diversity of 9 feces obtained from three species of African great apes, gorilla (Gorilla gorilla gorilla), chimpanzee (Pan troglodytes) and bonobo (Pan paniscus), using two mitochondrial amplifications for arthropods. A total of 1056 clones were sequenced for Cyt-b and COI gene libraries, which contained 50 and 56 operational taxonomic units (OTUs), respectively. BLAST research revealed that the OTUs belonged to 32 families from 5 orders (Diptera, Isoptera, Lepidoptera, Coleoptera, and Orthoptera). While ants were not detected by this method, the consumption of flies, beetles, moths, mosquitoes and termites was evident in these samples. Our findings indicate that molecular techniques can be used to analyze insect food items in wild animals.

  7. Ravens parallel great apes in flexible planning for tool-use and bartering.

    PubMed

    Kabadayi, Can; Osvath, Mathias

    2017-07-14

    The ability to flexibly plan for events outside of the current sensory scope is at the core of being human and is crucial to our everyday lives and society. Studies on apes have shaped a belief that this ability evolved within the hominid lineage. Corvids, however, have shown evidence of planning their food hoarding, although this has been suggested to reflect a specific caching adaptation rather than domain-general planning. Here, we show that ravens plan for events unrelated to caching-tool-use and bartering-with delays of up to 17 hours, exert self-control, and consider temporal distance to future events. Their performance parallels that seen in apes and suggests that planning evolved independently in corvids, which opens new avenues for the study of cognitive evolution. Copyright © 2017, American Association for the Advancement of Science.

  8. APE1/Ref-1 knockdown in pancreatic ductal adenocarcinoma: Characterizing gene expression changes and identifying novel pathways using single-cell RNA sequencing.

    PubMed

    Shah, Fenil; Goossens, Emery; Atallah, Nadia M; Grimard, Michelle; Kelley, Mark R; Fishel, Melissa L

    2017-09-18

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer-related pathways. Because APE1 is essential for cell viability, generation of APE1 knockout cell lines and determining a comprehensive list of genes regulated by APE1 has not been possible. To circumvent this challenge, we utilized single-cell RNA Sequencing to identify differentially expressed genes in relation to APE1 protein levels within the cell. Using a straight forward yet novel statistical design, we identified 2,837 genes whose expression is significantly changed following APE1 knockdown. Using this gene expression profile, we identified multiple new pathways not previously linked to APE1, including the EIF2 signaling and mTOR pathways and a number of mitochondrial-related pathways. We demonstrate that APE1 has an effect on modifying gene expression up to a threshold of APE1 expression, demonstrating that it is not necessary to completely knockout APE1 in cells to accurately study APE1 function. We validated the findings using a selection of the differentially expressed genes along with siRNA knockdown and qRT-PCR. Testing additional patient-derived pancreatic cancer cells reveal particular genes (ITGA1, TNFAIP2, COMMD7, RAB3D) that respond to APE1 knockdown similarly across all the cell lines. Furthermore, we verified that the redox function of APE1 was responsible for driving gene expression of mitochondrial genes such as PRDX5 and genes that are important for proliferation such as SIPA1 and RAB3D by treating with APE1 redox specific inhibitor, APX3330. Our study identifies several novel genes and pathways affected by APE1, as well as tumor sub-type specificity. These findings will allow for hypothesis driven approaches to generate combination therapies using, for example, APE1 inhibitor APX3330 with other approved FDA drugs in an innovative manner for pancreatic and other cancer

  9. Dental development and life history in living African and Asian apes.

    PubMed

    Kelley, Jay; Schwartz, Gary T

    2010-01-19

    Life-history inference is an important aim of paleoprimatology, but life histories cannot be discerned directly from the fossil record. Among extant primates, the timing of many life-history attributes is correlated with the age at emergence of the first permanent molar (M1), which can therefore serve as a means to directly compare the life histories of fossil and extant species. To date, M1 emergence ages exist for only a small fraction of extant primate species and consist primarily of data from captive individuals, which may show accelerated dental eruption compared with free-living individuals. Data on M1 emergence ages in wild great apes exist for only a single chimpanzee individual, with data for gorillas and orangutans being anecdotal. This paucity of information limits our ability to make life-history inferences using the M1 emergence ages of extinct ape and hominin species. Here we report reliable ages at M1 emergence for the orangutan, Pongo pygmaeus (4.6 y), and the gorilla, Gorilla gorilla (3.8 y), obtained from the dental histology of wild-shot individuals in museum collections. These ages and the one reported age at M1 emergence in a free-living chimpanzee of approximately 4.0 y are highly concordant with the comparative life histories of these great apes. They are also consistent with the average age at M1 emergence in relation to the timing of life-history events in modern humans, thus confirming the utility of M1 emergence ages for life-history inference and providing a basis for making reliable life-history inferences for extinct apes and hominins.

  10. Oreopithecus was a bipedal ape after all: Evidence from the iliac cancellous architecture

    PubMed Central

    Rook, Lorenzo; Bondioli, Luca; Köhler, Meike; Moyà-Solà, Salvador; Macchiarelli, Roberto

    1999-01-01

    Textural properties and functional morphology of the hip bone cancellous network of Oreopithecus bambolii, a 9- to 7-million-year-old Late Miocene hominoid from Italy, provide insights into the postural and locomotor behavior of this fossil ape. Digital image processing of calibrated hip bone radiographs reveals the occurrence of trabecular features, which, in humans and fossil hominids, are related to vertical support of the body weight, i.e., to bipedality. PMID:10411955

  11. Senile cataract and genetic polymorphisms of APE1, XRCC1 and OGG1.

    PubMed

    Wang, Chen; Lai, Qiaohong; Zhang, Shu; Hu, Jun

    2015-01-01

    Polymorphisms of DNA repair enzymes which may influence their repair efficiency lead to diseases, for example, senile cataract. In this study, we aimed to analyze the association of single nucleotide polymorphisms in AP endonuclease-1 (APE1), 8-oxoguanine glycosylase-1 (OGG1) and X-ray repair cross-complementing-1 (XRCC1) genes with the risk of age-related cataract in a Chinese population. Genotyping was carried out by the polymerase chain reaction and DNA sequencing on 402 cataract patients and 813 controls in this study. Differences in the frequencies were estimated by the chi-square test, and risk was estimated using unconditional logistic regression after adjusting for age and gender. Our results demonstrated there was a significant difference between the case and control groups in the APE1-141 G/G genotype (P=0.002). This difference still existed after adjusting for age and gender (P*=0.003). The APE1-141 T/T genotype and T allele frequencies were significantly higher in cataract patients, while the G/G genotype and G allele frequencies in patients were significantly lower than in controls (P < 0.05). The APE1-141 G/G genotype (OR, 0.49; 95% CI, 0.31-0.77) seems to have a protective role against cataract, and the T allele seems to have a deleterious role in the development of cataract. In OGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.

  12. Functional Implications of Human-Specific Changes in Great Ape microRNAs

    PubMed Central

    García-Ramallo, Eva; Torruella-Loran, Ignasi; Fernández-Bellon, Hugo; Abelló, Teresa; Kondova, Ivanela; Bontrop, Ronald; Hvilsom, Christina; Navarro, Arcadi; Marquès-Bonet, Tomàs; Espinosa-Parrilla, Yolanda

    2016-01-01

    microRNAs are crucial post-transcriptional regulators of gene expression involved in a wide range of biological processes. Although microRNAs are highly conserved among species, the functional implications of existing lineage-specific changes and their role in determining differences between humans and other great apes have not been specifically addressed. We analyzed the recent evolutionary history of 1,595 human microRNAs by looking at their intra- and inter-species variation in great apes using high-coverage sequenced genomes of 82 individuals including gorillas, orangutans, bonobos, chimpanzees and humans. We explored the strength of purifying selection among microRNA regions and found that the seed and mature regions are under similar and stronger constraint than the precursor region. We further constructed a comprehensive catalogue of microRNA species-specific nucleotide substitutions among great apes and, for the first time, investigated the biological relevance that human-specific changes in microRNAs may have had in great ape evolution. Expression and functional analyses of four microRNAs (miR-299-3p, miR-503-3p, miR-508-3p and miR-541-3p) revealed that lineage-specific nucleotide substitutions and changes in the length of these microRNAs alter their expression as well as the repertoires of target genes and regulatory networks. We suggest that the studied molecular changes could have modified crucial microRNA functions shaping phenotypes that, ultimately, became human-specific. Our work provides a frame to study the impact that regulatory changes may have in the recent evolution of our species. PMID:27105073

  13. Lineage-Specific Changes in Biomarkers in Great Apes and Humans

    PubMed Central

    Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

    2015-01-01

    Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans. PMID:26247603

  14. Human and great ape red blood cells differ in plasmalogen levels and composition.

    PubMed

    Moser, Ann B; Steinberg, Steven J; Watkins, Paul A; Moser, Hugo W; Ramaswamy, Krishna; Siegmund, Kimberly D; Lee, D Rick; Ely, John J; Ryder, Oliver A; Hacia, Joseph G

    2011-06-17

    Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease. In a human and great ape cohort, we measured the red blood cell (RBC) levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the sn-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the sn-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues. We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and rodents with plasmalogen disorders, we propose that cross

  15. Lineage-Specific Changes in Biomarkers in Great Apes and Humans.

    PubMed

    Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

    2015-01-01

    Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.

  16. Humans and Great Apes Cohabiting the Forest Ecosystem in Central African Republic Harbour the Same Hookworms

    PubMed Central

    Hasegawa, Hideo; Modrý, David; Kitagawa, Masahiro; Shutt, Kathryn A.; Todd, Angelique; Kalousová, Barbora; Profousová, Ilona; Petrželková, Klára J.

    2014-01-01

    Background Hookworms are important pathogens of humans. To date, Necator americanus is the sole, known species of the genus Necator infecting humans. In contrast, several Necator species have been described in African great apes and other primates. It has not yet been determined whether primate-originating Necator species are also parasitic in humans. Methodology/Principal Findings The infective larvae of Necator spp. were developed using modified Harada-Mori filter-paper cultures from faeces of humans and great apes inhabiting Dzanga-Sangha Protected Areas, Central African Republic. The first and second internal transcribed spacers (ITS-1 and ITS-2) of nuclear ribosomal DNA and partial cytochrome c oxidase subunit 1 (cox1) gene of mtDNA obtained from the hookworm larvae were sequenced and compared. Three sequence types (I–III) were recognized in the ITS region, and 34 cox1 haplotypes represented three phylogenetic groups (A–C). The combinations determined were I-A, II-B, II-C, III-B and III-C. Combination I-A, corresponding to N. americanus, was demonstrated in humans and western lowland gorillas; II-B and II-C were observed in humans, western lowland gorillas and chimpanzees; III-B and III-C were found only in humans. Pairwise nucleotide difference in the cox1 haplotypes between the groups was more than 8%, while the difference within each group was less than 2.1%. Conclusions/Significance The distinctness of ITS sequence variants and high number of pairwise nucleotide differences among cox1 variants indicate the possible presence of several species of Necator in both humans and great apes. We conclude that Necator hookworms are shared by humans and great apes co-habiting the same tropical forest ecosystems. PMID:24651493

  17. The thumb of Miocene apes: new insights from Castell de Barberà (Catalonia, Spain).

    PubMed

    Almécija, Sergio; Alba, David M; Moyà-Solà, Salvador

    2012-07-01

    Primate hands display a major selective compromise between locomotion and manipulation. The thumb may or may not participate in locomotion, but it plays a central role in most manipulative activities. Understanding whether or not the last common ancestor of humans and Pan displayed extant-ape-like hand proportions (i.e., relatively long fingers and a short thumb) can be clarified by the analysis of Miocene ape hand remains. Here we describe new pollical remains-a complete proximal phalanx and a partial distal phalanx-from the middle/late Miocene site of Castell de Barberà (ca., 11.2-10.5 Ma, Vallès-Penedès Basin), and provide morphometric and qualitative comparisons with other available Miocene specimens as well as extant catarrhines (including humans). Our results show that all available Miocene taxa (Proconsul, Nacholapithecus, Afropithecus, Sivapithecus, Hispanopithecus, Oreopithecus, and the hominoid from Castell de Barberà) share a similar phalangeal thumb morphology: the phalanges are relatively long, and the proximal phalanges have a high degree of curvature, marked insertions for the flexor muscles, a palmarly bent trochlea and a low basal height. All these features suggest that these Miocene apes used their thumb with an emphasis on flexion, most of them to powerfully assist the fingers during above-branch, grasping arboreal locomotion. Moreover, in terms of relative proximal phalangeal length, the thumb of Miocene taxa is intermediate between the long-thumbed humans and the short-thumbed extant apes. Together with previous evidence, this suggests that a moderate-length hand with relatively long thumb-involved in locomotion-is the original hand morphotype for the Hominidae. Copyright © 2012 Wiley Periodicals, Inc.

  18. Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes.

    PubMed

    Dasmeh, Pouria; Kepp, Kasper P

    2017-08-01

    Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million years, significantly higher than in other primates and rodents, although these paradoxically generally evolve much faster. The high evolutionary rate was partly due to relaxation of some selection pressures and partly to distinct positive selection of SOD1 in great apes. We then show that higher stability and net charge and changes at the dimer interface were selectively introduced upon separation from old world monkeys and lesser apes (gibbons). Consequently, human, chimpanzee and gorilla SOD1s have a net charge of -6 at physiological pH, whereas the closely related gibbons and macaques have -3. These features consistently point towards selection against the malicious aggregation effects of elevated SOD1 levels in long-living great apes. The findings mirror the impact of human SOD1 mutations that reduce net charge and/or stability and cause ALS, a motor neuron disease characterized by oxidative stress and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging.

  19. Shared pattern of endocranial shape asymmetries among great apes, anatomically modern humans, and fossil hominins.

    PubMed

    Balzeau, Antoine; Gilissen, Emmanuel; Grimaud-Hervé, Dominique

    2011-01-01

    Anatomical asymmetries of the human brain are a topic of major interest because of their link with handedness and cognitive functions. Their emergence and occurrence have been extensively explored in human fossil records to document the evolution of brain capacities and behaviour. We quantified for the first time antero-posterior endocranial shape asymmetries in large samples of great apes, modern humans and fossil hominins through analysis of "virtual" 3D models of skull and endocranial cavity and we statistically test for departures from symmetry. Once based on continuous variables, we show that the analysis of these brain asymmetries gives original results that build upon previous analysis based on discrete traits. In particular, it emerges that the degree of petalial asymmetries differs between great apes and hominins without modification of their pattern. We indeed demonstrate the presence of shape asymmetries in great apes, with a pattern similar to modern humans but with a lower variation and a lower degree of fluctuating asymmetry. More importantly, variations in the position of the frontal and occipital poles on the right and left hemispheres would be expected to show some degree of antisymmetry when population distribution is considered, but the observed pattern of variation among the samples is related to fluctuating asymmetry for most of the components of the petalias. Moreover, the presence of a common pattern of significant directional asymmetry for two components of the petalias in hominids implicates that the observed traits were probably inherited from the last common ancestor of extant African great apes and Homo sapiens.These results also have important implications for the possible relationships between endocranial shape asymmetries and functional capacities in hominins. It emphasizes the uncoupling between lateralized activities, some of them well probably distinctive to Homo, and large-scale cerebral lateralization itself, which is not unique

  20. eulerAPE: Drawing Area-Proportional 3-Venn Diagrams Using Ellipses

    PubMed Central

    Micallef, Luana; Rodgers, Peter

    2014-01-01

    Venn diagrams with three curves are used extensively in various medical and scientific disciplines to visualize relationships between data sets and facilitate data analysis. The area of the regions formed by the overlapping curves is often directly proportional to the cardinality of the depicted set relation or any other related quantitative data. Drawing these diagrams manually is difficult and current automatic drawing methods do not always produce appropriate diagrams. Most methods depict the data sets as circles, as they perceptually pop out as complete distinct objects due to their smoothness and regularity. However, circles cannot draw accurate diagrams for most 3-set data and so the generated diagrams often have misleading region areas. Other methods use polygons to draw accurate diagrams. However, polygons are non-smooth and non-symmetric, so the curves are not easily distinguishable and the diagrams are difficult to comprehend. Ellipses are more flexible than circles and are similarly smooth, but none of the current automatic drawing methods use ellipses. We present eulerAPE as the first method and software that uses ellipses for automatically drawing accurate area-proportional Venn diagrams for 3-set data. We describe the drawing method adopted by eulerAPE and we discuss our evaluation of the effectiveness of eulerAPE and ellipses for drawing random 3-set data. We compare eulerAPE and various other methods that are currently available and we discuss differences between their generated diagrams in terms of accuracy and ease of understanding for real world data. PMID:25032825

  1. Dental development and life history in living African and Asian apes

    PubMed Central

    Kelley, Jay; Schwartz, Gary T.

    2009-01-01

    Life-history inference is an important aim of paleoprimatology, but life histories cannot be discerned directly from the fossil record. Among extant primates, the timing of many life-history attributes is correlated with the age at emergence of the first permanent molar (M1), which can therefore serve as a means to directly compare the life histories of fossil and extant species. To date, M1 emergence ages exist for only a small fraction of extant primate species and consist primarily of data from captive individuals, which may show accelerated dental eruption compared with free-living individuals. Data on M1 emergence ages in wild great apes exist for only a single chimpanzee individual, with data for gorillas and orangutans being anecdotal. This paucity of information limits our ability to make life-history inferences using the M1 emergence ages of extinct ape and hominin species. Here we report reliable ages at M1 emergence for the orangutan, Pongo pygmaeus (4.6 y), and the gorilla, Gorilla gorilla (3.8 y), obtained from the dental histology of wild-shot individuals in museum collections. These ages and the one reported age at M1 emergence in a free-living chimpanzee of approximately 4.0 y are highly concordant with the comparative life histories of these great apes. They are also consistent with the average age at M1 emergence in relation to the timing of life-history events in modern humans, thus confirming the utility of M1 emergence ages for life-history inference and providing a basis for making reliable life-history inferences for extinct apes and hominins. PMID:20080537

  2. Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan

    PubMed Central

    Lai, Ching-Yu; Hsieh, Ling-Ling; Tang, Reiping; Santella, Regina M; Chang-Chieh, Chung Rong; Yeh, Chih-Ching

    2016-01-01

    AIM: To evaluate the effects of OGG1 (Ser326Cys, 11657A/G, and Arg154His) and APE1 (Asp148Glu, and T-656G) polymorphisms on colorectal cancer (CRC) risk. METHODS: We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction. Unconditional logistic regressions were used for calculating ORs and 95%CIs to determine the association between the genetic polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE software. Moreover, stratification analyses on the basis of sex, age at diagnosis, and tumor subsite and stage were performed. RESULTS: The CRC risk was higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype (OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage III + IV cancer (OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype. In addition, OGG1 11657G allele carriers had a 41% reduced CRC risk among stage 0-II patients (OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher among females with the APE1 Glu allele (OR = 1.41, 95%CI: 1.02-1.96). The APE1 148Glu/-656G haplotype was also associated with a significant CRC risk in females (OR = 1.36, 95%CI: 1.03-1.78). CONCLUSION: OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC in the Taiwanese population. PMID:27022219

  3. Great apes can defer exchange: a replication with different results suggesting future oriented behavior.

    PubMed

    Osvath, Mathias; Persson, Tomas

    2013-01-01

    The topic of cognitive foresight in non-human animals has received considerable attention in the last decade. The main questions concern whether the animals can prepare for upcoming situations which are, to various degrees, contextually or sensorially detached from the situation in which the preparations are made. Studies on great apes have focused on tool-related tasks, e.g., the ability to select a tool which is functional only in the future. Dufour and Sterck (2008), however, investigated whether chimpanzees were also able to prepare for a future exchange with a human: an object exchanged for a food item. The study included extensive training on the exchangeable item, which is traditionally not compatible with methods for studying planning abilities, as associative learning cannot be precluded. Nevertheless, despite this training, the chimpanzees could not solve the deferred exchange task. Given that great apes can plan for tool use, these results are puzzling. In addition, claims that great ape foresight is highly limited has been based on this study (Suddendorf and Corballis, 2010). Here we partly replicated Dufour and Sterck's study to discern whether temporally deferred and spatially displaced exchange tasks are beyond the capabilities of great apes. In addition to chimpanzees we tested orangutans. One condition followed the one used by Dufour and Sterck, in which the exchange items, functional only in the future, are placed at a location that freely allows for selections by the subjects. In order to test the possibility that the choice set-up could explain the negative results in Dufour and Sterck's study, our second condition followed a method used in the planning study by Osvath and Osvath (2008), where the subjects make a forced one-item-choice from a tray. We found that it is within the capabilities of chimpanzees and orangutans to perform deferred exchange in both conditions.

  4. Great apes can defer exchange: a replication with different results suggesting future oriented behavior

    PubMed Central

    Osvath, Mathias; Persson, Tomas

    2013-01-01

    The topic of cognitive foresight in non-human animals has received considerable attention in the last decade. The main questions concern whether the animals can prepare for upcoming situations which are, to various degrees, contextually or sensorially detached from the situation in which the preparations are made. Studies on great apes have focused on tool-related tasks, e.g., the ability to select a tool which is functional only in the future. Dufour and Sterck (2008), however, investigated whether chimpanzees were also able to prepare for a future exchange with a human: an object exchanged for a food item. The study included extensive training on the exchangeable item, which is traditionally not compatible with methods for studying planning abilities, as associative learning cannot be precluded. Nevertheless, despite this training, the chimpanzees could not solve the deferred exchange task. Given that great apes can plan for tool use, these results are puzzling. In addition, claims that great ape foresight is highly limited has been based on this study (Suddendorf and Corballis, 2010). Here we partly replicated Dufour and Sterck's study to discern whether temporally deferred and spatially displaced exchange tasks are beyond the capabilities of great apes. In addition to chimpanzees we tested orangutans. One condition followed the one used by Dufour and Sterck, in which the exchange items, functional only in the future, are placed at a location that freely allows for selections by the subjects. In order to test the possibility that the choice set-up could explain the negative results in Dufour and Sterck's study, our second condition followed a method used in the planning study by Osvath and Osvath (2008), where the subjects make a forced one-item-choice from a tray. We found that it is within the capabilities of chimpanzees and orangutans to perform deferred exchange in both conditions. PMID:24106486

  5. Human and great ape red blood cells differ in plasmalogen levels and composition

    PubMed Central

    2011-01-01

    Background Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease. Results In a human and great ape cohort, we measured the red blood cell (RBC) levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the sn-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the sn-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues. Conclusion We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and rodents with plasmalogen

  6. Toward granting linguistic competence to apes: A review of Savage-Rumbaugh et al.'s Language Comprehension in Ape and Child1

    PubMed Central

    Sundberg, Mark L.

    1996-01-01

    Savage-Rumbaugh et al.'s (1993) monograph describes a study that compared the language comprehension of an 8-year-old ape (a bonobo named Kanzi) with that of a normal 2-year-old human (Alia). The primary purpose of the research was to see if Kanzi could comprehend novel and compound spoken English commands without imitative prompts, contrived reinforcement contingencies, or explicit training procedures. As it turned out, Kanzi acquired a complex comprehension repertoire in a pattern similar to the human child's and even performed better than the human child in many cases. Although this review describes these empirical results favorably, it questions the authors' claim that the subjects learned the repertoire on their own, without reinforcement or training. A close examination of the subjects' histories and of the procedures, transcripts, and videos suggested that the training and testing procedures involved a number of independent variables and processes that were not discussed by the authors, including conditioned reinforcement and punishment, verbal prompts, stimulus control, establishing operations, and extinction. Nonetheless, the methodological and empirical contributions to ape and human language research are substantial and deserve behavior analysts' attention and support. Behavior analysts could contribute to this kind of research by applying the analytic and conceptual tools of behavior analysis in general and the concepts from Verbal Behavior (Skinner, 1957) in particular.

  7. Onset and early use of gestural communication in nonhuman great apes.

    PubMed

    Schneider, Christel; Call, Josep; Liebal, Katja

    2012-02-01

    The early gesturing of six bonobos, eight chimpanzees, three gorillas, and eight orangutans was systematically documented using focal animal sampling. Apes' were observed during their first 20 months of life in an effort to investigate: (i) the onset of gesturing; (ii) the order in which signals of different sensory modalities appear; (iii) the extent to which infants make use of these modalities in their early signaling; and (iv) the behavioral contexts where signals are employed. Orangutans differed in important gestural characteristics to African ape species. Most notably, they showed the latest gestural onset and were more likely to use their early signals in food-related interactions. Tactile and visual signals appeared similarly early across all four species. In African apes, however, visual signaling gained prominence over time while tactile signaling decreased. These findings suggest that motor ability, which encourages independence from caregivers, is an important antecedent, among others, in gestural onset and development, a finding which warrants further investigation. © 2011 Wiley Periodicals, Inc.

  8. A Burst of Segmental Duplications in the African Great Ape Ancestor

    PubMed Central

    Marques-Bonet, Tomas; Kidd, Jeffrey M.; Ventura, Mario; Graves, Tina A.; Cheng, Ze; Hillier, LaDeanna W.; Jiang, Zhaoshi; Baker, Carl; Malfavon-Borja, Ray; Fulton, Lucinda A.; Alkan, Can; Aksay, Gozde; Girirajan, Santhosh; Siswara, Priscillia; Chen, Lin; Cardone, Maria Francesca; Navarro, Arcadi; Mardis, Elaine R.; Wilson, Richard K.; Eichler, Evan E.

    2009-01-01

    Wilson and King were among the first to recognize that the extent of phenotypic change between humans and great apes was dissonant with the rate of molecular change. Proteins are virtually identical1,2; cytogenetically there are few rearrangements that distinguish ape-human chromosomes3; rates of single-basepair change4-7 and retroposon activity8-10 have slowed particularly within hominid lineages when compared to rodents or monkeys. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orangutan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of basepairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage-specific rate estimates even after accounting for copy-number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene-containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single basepair mutations, there has been a genomic burst of duplication activity at this period during human evolution. PMID:19212409

  9. Differential resource utilization by extant great apes and australopithecines: towards solving the C4 conundrum.

    PubMed

    Sponheimer, Matt; Lee-Thorp, Julia A

    2003-09-01

    Morphological and biogeochemical evidence suggest that australopithecines had diets markedly different from those of extant great apes. Stable carbon isotope analysis, for example, has shown that significant amounts of the carbon consumed by australopithecines were derived from C(4) photosynthesis in plants. This means that australopithecines were eating large quantities of C(4) plants such as tropical grasses and sedges, or were eating animals that were themselves eating C(4) plants. In contrast, there is no evidence that modern apes consume appreciable amounts of any of these foods, even in the most arid extents of their ranges where these foods are most prevalent. Environmental reconstructions of early australopithecine environments overlap with modern chimpanzee habitats. This, in conjunction with the stable isotope evidence, suggests that australopithecines and great apes, even in similar environments, would utilize available resources differently. Thus, the desire or capacity to use C(4) foods may be a basal character of our lineage. We do not know, however, which of the nutritionally disparate C(4) foods were utilized by hominids. Here we discuss which C(4) resources were most likely consumed by australopithecines, as well as the potential nutritional, physiological, and social consequences of eating these foods.

  10. Morphological analysis of the hindlimb in apes and humans. I. Muscle architecture

    PubMed Central

    Payne, R C; Crompton, R H; Isler, K; Savage, R; Vereecke, E E; Günther, M M; Thorpe, S K S; D'Août, K

    2006-01-01

    We present quantitative data on the hindlimb musculature of Pan paniscus, Gorilla gorilla gorilla, Gorilla gorilla graueri, Pongo pygmaeus abelii and Hylobates lar and discuss the findings in relation to the locomotor habits of each. Muscle mass and fascicle length data were obtained for all major hindlimb muscles. Physiological cross-sectional area (PCSA) was estimated. Data were normalized assuming geometric similarity to allow for comparison of animals of different size/species. Muscle mass scaled closely to (body mass)1.0 and fascicle length scaled closely to (body mass)0.3 in most species. However, human hindlimb muscles were heavy and had short fascicles per unit body mass when compared with non-human apes. Gibbon hindlimb anatomy shared some features with human hindlimbs that were not observed in the non-human great apes: limb circumferences tapered from proximal-to-distal, fascicle lengths were short per unit body mass and tendons were relatively long. Non-human great ape hindlimb muscles were, by contrast, characterized by long fascicles arranged in parallel, with little/no tendon of insertion. Such an arrangement of muscle architecture would be useful for locomotion in a three dimensionally complex arboreal environment. PMID:16761973

  11. Wolfgang Köhler's The Mentality of Apes and the animal psychology of his time.

    PubMed

    Ruiz, Gabriel; Sánchez, Natividad

    2014-10-28

    In 1913, the Anthropoid Station for psychological and physiological research in chimpanzees and other apes was founded by the Royal Prussian Academy of Sciences (Berlin) near La Orotava, Tenerife. Eugene Teuber, its first director, began his work at the Station with several studies of anthropoid apes' natural behavior, particularly chimpanzee body language. In late 1913, the psychologist Wolfgang Köhler, the second and final director of the Station, arrived in Tenerife. During his stay in the Canary Islands, Köhler conducted a series of studies on intelligent behavior in chimpanzees that would become classics in the field of comparative psychology. Those experiments were at the core of his book Intelligenzprüfungen an Menschenaffen (The Mentality of Apes), published in 1921. This paper analyzes Köhler's experiments and notions of intelligent behavior in chimpanzees, emphasizing his distinctly descriptive approach to these issues. It also makes an effort to elucidate some of the theoretical ideas underpinning Köhler's work. The ultimate goal of this paper is to assess the historical significance of Köhler's book within the context of the animal psychology of his time.

  12. GAPforAPE: an augmented browsing system to improve Web 2.0 accessibility

    NASA Astrophysics Data System (ADS)

    Mirri, Silvia; Salomoni, Paola; Prandi, Catia; Muratori, Ludovico Antonio

    2012-09-01

    The Web 2.0 evolution has spread more interactive technologies which affected accessibility for users who navigate the Web by using assistive technologies. In particular, the partial download of new data, the continuous refreshing, and the massive use of scripting can represent significant barriers especially for people with visual impairments, who enjoy the Web by means of screen readers. On the other hand, such technologies can be an opportunity, because they can provide a new means of transcoding Web content, making the Web more accessible. In this article we present GAPforAPE, an augmented browsing system (based on Web browsers extensions) which offers a user's profiling system and transcodes Web content according to constrains declared by users: the same Web page is provided to any user, but GAPforAPE computes adequate customizations, by exploiting scripting technologies which usually affect Web pages accessibility. GAPforAPE imitates screen readers behavior: it applies a specific set of transcoding scripts devoted to a given Web site, when available, and a default set of transcoding operations otherwise. The continuous and quick evolution of the Web has shown that a crowdsourcing system is a desirable solution, letting the transcoding scripts evolve in the same way.

  13. Great Apes and Biodiversity Offset Projects in Africa: The Case for National Offset Strategies

    PubMed Central

    Kormos, Rebecca; Kormos, Cyril F.; Humle, Tatyana; Lanjouw, Annette; Rainer, Helga; Victurine, Ray; Mittermeier, Russell A.; Diallo, Mamadou S.; Rylands, Anthony B.; Williamson, Elizabeth A.

    2014-01-01

    The development and private sectors are increasingly considering “biodiversity offsets” as a strategy to compensate for their negative impacts on biodiversity, including impacts on great apes and their habitats in Africa. In the absence of national offset policies in sub-Saharan Africa, offset design and implementation are guided by company internal standards, lending bank standards or international best practice principles. We examine four projects in Africa that are seeking to compensate for their negative impacts on great ape populations. Our assessment of these projects reveals that not all apply or implement best practices, and that there is little standardization in the methods used to measure losses and gains in species numbers. Even if they were to follow currently accepted best-practice principles, we find that these actions may still fail to contribute to conservation objectives over the long term. We advocate for an alternative approach in which biodiversity offset and compensation projects are designed and implemented as part of a National Offset Strategy that (1) takes into account the cumulative impacts of development in individual countries, (2) identifies priority offset sites, (3) promotes aggregated offsets, and (4) integrates biodiversity offset and compensation projects with national biodiversity conservation objectives. We also propose supplementary principles necessary for biodiversity offsets to contribute to great ape conservation in Africa. Caution should still be exercised, however, with regard to offsets until further field-based evidence of their effectiveness is available. PMID:25372894

  14. Great apes and biodiversity offset projects in Africa: the case for national offset strategies.

    PubMed

    Kormos, Rebecca; Kormos, Cyril F; Humle, Tatyana; Lanjouw, Annette; Rainer, Helga; Victurine, Ray; Mittermeier, Russell A; Diallo, Mamadou S; Rylands, Anthony B; Williamson, Elizabeth A

    2014-01-01

    The development and private sectors are increasingly considering "biodiversity offsets" as a strategy to compensate for their negative impacts on biodiversity, including impacts on great apes and their habitats in Africa. In the absence of national offset policies in sub-Saharan Africa, offset design and implementation are guided by company internal standards, lending bank standards or international best practice principles. We examine four projects in Africa that are seeking to compensate for their negative impacts on great ape populations. Our assessment of these projects reveals that not all apply or implement best practices, and that there is little standardization in the methods used to measure losses and gains in species numbers. Even if they were to follow currently accepted best-practice principles, we find that these actions may still fail to contribute to conservation objectives over the long term. We advocate for an alternative approach in which biodiversity offset and compensation projects are designed and implemented as part of a National Offset Strategy that (1) takes into account the cumulative impacts of development in individual countries, (2) identifies priority offset sites, (3) promotes aggregated offsets, and (4) integrates biodiversity offset and compensation projects with national biodiversity conservation objectives. We also propose supplementary principles necessary for biodiversity offsets to contribute to great ape conservation in Africa. Caution should still be exercised, however, with regard to offsets until further field-based evidence of their effectiveness is available.

  15. Gestural and symbolic development among apes and humans: support for a multimodal theory of language evolution

    PubMed Central

    Gillespie-Lynch, Kristen; Greenfield, Patricia M.; Lyn, Heidi; Savage-Rumbaugh, Sue

    2014-01-01

    What are the implications of similarities and differences in the gestural and symbolic development of apes and humans?This focused review uses as a starting point our recent study that provided evidence that gesture supported the symbolic development of a chimpanzee, a bonobo, and a human child reared in language-enriched environments at comparable stages of communicative development. These three species constitute a complete clade, species possessing a common immediate ancestor. Communicative behaviors observed among all species in a clade are likely to have been present in the common ancestor. Similarities in the form and function of many gestures produced by the chimpanzee, bonobo, and human child suggest that shared non-verbal skills may underlie shared symbolic capacities. Indeed, an ontogenetic sequence from gesture to symbol was present across the clade but more pronounced in child than ape. Multimodal expressions of communicative intent (e.g., vocalization plus persistence or eye-contact) were normative for the child, but less common for the apes. These findings suggest that increasing multimodal expression of communicative intent may have supported the emergence of language among the ancestors of humans. Therefore, this focused review includes new studies, since our 2013 article, that support a multimodal theory of language evolution. PMID:25400607

  16. Bridging the gap: parkour athletes provide new insights into locomotion energetics of arboreal apes.

    PubMed

    Halsey, Lewis G; Coward, Samuel R L; Thorpe, Susannah K S

    2016-11-01

    The tree canopy is an energetically challenging environment to traverse. Along with compliant vegetation, gaps in the canopy can prove energetically costly if they force a route-extending detour. Arboreal apes exhibit diverse locomotion strategies, including for gap crossing. Which one they employ in any given scenario may be influenced by the energy costs to do so, which are affected by the details of the immediate environment in combination with their body size. Measuring energetics of arboreal apes is not tractable; thus our knowledge in this area is limited. We devised a novel, custom-made experimental set-up to record the energy expenditure of parkour athletes tree-swaying, jumping and vertical climbing. The latter strategy was vastly more expensive, indicating that when energy economy is the focus arboreal apes will prioritize routes that limit height changes. Whether tree-swaying or jumping was most economical for the athletes depended upon interactions between tree stiffness, the distance to cross, number of tree-sways required and their own mass. Updated analysis of previous interspecific correlations suggests that whether the relative costs to vertical climb are size-invariant across primate species is complicated by details of the climbing context. © 2016 The Author(s).

  17. Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans

    NASA Astrophysics Data System (ADS)

    Varki, Ajit

    2004-06-01

    At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.

  18. Skeletal development of hallucal tarsometatarsal joint curvature and angulation in extant apes and modern humans.

    PubMed

    Gill, Corey M; Bredella, Miriam A; DeSilva, Jeremy M

    2015-11-01

    The medial cuneiform, namely the curvature and angulation of its distal facet with metatarsal 1, is crucial as a stabilizer in bipedal locomotion and an axis upon which the great toe medially deviates during arboreal locomotion in extant apes. Previous work has shown that facet curvature and angulation in adult dry-bone specimens can distinguish African apes from Homo, and can even distinguish among species of Gorilla. This study provides the first ontogenetic assessment of medial cuneiform curvature and angulation in juvenile (n = 68) and adult specimens (n = 102) using computed tomography in humans and extant ape specimens, including Pongo. Our data find that modern human juveniles initially have a convex and slightly medially oriented osseous surface of the developing medial cuneiform distal facet that flattens and becomes more distally oriented with age. The same pattern (though of a different magnitude) occurs developmentally in the chimpanzee medial cuneiform, but not in Gorilla or Pongo, whose medial cuneiform facet angulation remains unchanged ontogenetically. These data suggest that the medial cuneiform ossifies in a distinguishable pattern between Pongo, Gorilla, Pan, and Homo, which may in part be due to subtle differences in the loading environment at the hallucal tarsometatarsal joint-a finding that has important implications for interpreting fossil medial cuneiforms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Fossil apes from the Vallès-Penedès Basin.

    PubMed

    Alba, David M

    2012-11-01

    Currently restricted to Southeast Asia and Africa, extant hominoids are the remnants of a group that was much more diverse during the Miocene. Apes initially diversified in Africa during the early Miocene, but by the middle Miocene they extended their geographical range into Eurasia, where they experienced an impressive evolutionary radiation. Understanding the role of Eurasian hominoids in the origin and evolution of the great-ape-and-human clade (Hominidae) is partly hampered by phylogenetic uncertainties, the scarcity and incompleteness of fossil remains, the current restricted diversity of the group, and pervasive homoplasy. Nevertheless, scientific knowledge of the Eurasian hominoid radiation has significantly improved during the last decade. In the case of Western Europe, this has been due to the discovery of new remains from the Vallès-Penedès Basin (Catalonia, Spain). Here, I review the fossil record of Vallès-Penedès apes and consider its implications. Although significant disagreements persist among scholars, some important lessons can be learned regarding the evolutionary history of the closest living relatives of humans. Copyright © 2012 Wiley Periodicals, Inc.

  20. BLOOD PRODUCT TRANSFUSIONS IN GREAT APES: A RETROSPECTIVE REVIEW OF 12 CASES.

    PubMed

    Hahn, Alicia; Sturgeon, Ginger; Rossi, Joseph

    2017-06-01

    Although the administration of blood and blood products can be lifesaving, transfusions in exotic species are less common because of the lack of knowledge of a species' blood groups, the availability of species-specific donors, and possible adverse effects. Recently, blood groups were elucidated in great apes; however, few reports have been published regarding actual transfusion situations in these species. This information is critical because poorly executed transfusions can compromise already weakened patients or result in the death of the recipient. In 2014, a retrospective survey of U.S. zoos housing great apes received 45 of 67 responses; from which, 12 transfusion cases in great apes were identified, including Sumatran orangutans ( Pongo pygmaeus sumatraensis, n = 4), chimpanzee ( Pan troglodytes , n = 1), and western lowland gorillas ( Gorilla gorilla gorilla, n = 7). These animals, ranging from birth to 31 yr, received intravenous transfusions of whole blood, packed red blood cells, or human albumin. Overall, animals that received transfusions for anemia because of chronic illness or blood loss survived, but those individuals with concurrent life-threatening issues did not survive. No adverse reactions related to the transfusion occurred, except in two orangutans given human albumin.

  1. Evaluation of effectiveness, safety and reliability of intramuscular medetomidine-ketamine for captive great apes.

    PubMed

    Adami, C; Wenker, C; Hoby, S; Bergadano, A

    2012-08-25

    Twenty great apes (six orangutans, eight chimpanzees and six gorillas) were anaesthetised prior to being transported for undergoing diagnostic and interventional procedures. Anaesthesia was induced with a combination of medetomidine and ketamine administered intramuscularly through a dart syringe. The onset of anaesthesia varied among apes: the mean (±sd) time from darting to recumbency was 12.13 (±1.9), 18.5 (±8.7) and 22.2 (±9.2) minutes in chimpanzees, orangutans and gorillas, respectively. The depth of anaesthesia was sufficient to allow safe removal of the animals from the enclosure, intravenous catheter placement and manipulation; however, the anaesthetic effect was short-acting (20 (±7) minutes in orangutans, 16 (±14) in gorillas, and 10 (±4) minutes in chimpanzees, respectively) and isoflurane administration was necessary in the majority of the apes to prolong the duration of anaesthesia, especially when lengthier procedures were performed. The sedative effect of medetomidine was reversed at the end of each procedure with atipamezole, and recovery was smooth and uneventful for all animals.

  2. Great apes use weight as a cue to find hidden food.

    PubMed

    Schrauf, Cornelia; Call, Josep

    2011-04-01

    Bonobos (Pan paniscus; n=5), orangutans (Pongo pygmaeus abelii; n=6), and a gorilla (Gorilla gorilla gorilla; n=1) were presented with two opaque cups, one empty and one baited (containing two bananas). Subjects had to independently gain weight information about the contents of the cups to find the hidden food. Six apes attained above chance level within a total of 16 trials. Successful subjects spontaneously adopted the method of successively lifting the cups and thus comparing their weight before making a choice. Prior to testing, these apes had participated in a weight discrimination task. To rule out that a subject's good performance was influenced by previous experience in weight experiments, we ran a second test in which the same task was presented to a group of chimpanzees (Pan troglodytes; n=9) who were naïve to weight experiments. These subjects also participated in an additional test condition in which the same problem was presented based on learning to associate arbitrary visual stimuli. The results show that experience did not affect performance because the nine naïve subjects were equally able to find the food when the task stimuli held a causal relation (i.e. weight indicates the hidden food). Interestingly, only one of the naïve subjects solved the task when the task elements held an arbitrary relation (i.e. certain visual pattern indicates food). Our results confirm previous findings that apes perform better in problems grounded on causal compared to arbitrary relations.

  3. Yerkes, Hamilton and the experimental study of the ape mind: from evolutionary psychiatry to eugenic politics.

    PubMed

    Thomas, Marion

    2006-06-01

    Robert Yerkes is a pivotal figure in American psychology and primatology in the first half of the twentieth century. As is well known, Yerkes first studied ape intelligence in 1915, on a visit to the private California laboratory of the psychiatrist Gilbert Hamilton, a former student. Less widely appreciated is how far the work done at the Hamilton lab, in its aims and ambitions as well as its techniques, served as a template for much of Yerkes's research thereafter. This paper uses the Hamilton-Yerkes relationship to re-examine Yerkes's career and, more generally, that of American psychology in the early twentieth century. Three points especially are emphasized: first, the role of Freudian psychoanalysis as a spur to Hamilton's experimental studies of ape intelligence; second, the importance of Hamilton's laboratory, with its semi-wild population of monkeys and ape, as a model for Yerkes's efforts to create a laboratory of his own; and third, the influence on Yerkes of Hamilton's optimism about experimental psychological studies of nonhuman primates as a source of lessons beneficial to a troubled human world.

  4. Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure.

    PubMed

    Ma, Huaxian; Wang, Jianling; Abdel-Rahman, Sherif Z; Boor, Paul J; Khan, M Firoze

    2013-03-15

    Mechanisms by which aniline exposure elicits splenotoxicity, especially a tumorigenic response, are not well-understood. Earlier, we have shown that aniline exposure leads to oxidative DNA damage and up-regulation of OGG1 and NEIL1/2 DNA glycosylases in rat spleen. However, the contribution of endonuclease III homolog 1 (NTH1) and apurinic/apyrimidinic endonuclease 1 (APE1) in the repair of aniline-induced oxidative DNA damage in the spleen is not known. This study was, therefore, focused on examining whether NTH1 and APE1 contribute to the repair of oxidative DNA lesions in the spleen, in an experimental condition preceding tumorigenesis. To achieve this, male SD rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. By quantitating the cleavage products, the activities of NTH1 and APE1 were assayed using substrates containing thymine glycol (Tg) and tetrahydrofuran, respectively. Aniline treatment led to significant increases in NTH1- and APE1-mediated BER activity in the nuclear extracts of spleen of aniline-treated rats compared to the controls. NTH1 and APE1 mRNA expression in the spleen showed 2.9- and 3.2-fold increases, respectively, in aniline-treated rats compared to the controls. Likewise, Western blot analysis showed that protein expression of NTH1 and APE1 in the nuclear extracts of spleen from aniline-treated rats was 1.9- and 2.7-fold higher than the controls, respectively. Immunohistochemistry indicated that aniline treatment also led to stronger immunoreactivity for both NTH1 and APE1 in the spleens, confined to the red pulp areas. These results, thus, show that aniline exposure is associated with induction of NTH1 and APE1 in the spleen. The increased repair activity of NTH1 and APE1 could be an important mechanism for the removal of oxidative DNA lesions. These findings thus identify a novel mechanism through which NTH1 and APE1 may regulate the repair of

  5. Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer

    PubMed Central

    Qing, Yi; Li, Qing; Ren, Tao; Xia, Wei; Peng, Yu; Liu, Gao-Lei; Luo, Hao; Yang, Yu-Xin; Dai, Xiao-Yan; Zhou, Shu-Feng; Wang, Dong

    2015-01-01

    Introduction Gastric cancer is a fatal malignancy with a rising incidence rate. Effective methods for early diagnosis, monitoring metastasis, and prognosis are currently unavailable for gastric cancer. In this study, we examined the association of programmed death ligand-1 (PD-L1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with the prognosis of gastric cancer. Methods The expressions of PD-L1 and APE1 were detected by immunohistochemistry in 107 cases of human gastric carcinoma. The correlation of PD-L1 and APE1 expression with the clinicopathologic features of gastric carcinoma was analyzed by SPSS version 19.0. Results The positive expression rates of PD-L1 and APE1 in gastric cancer tissues were 50.5% (54/107) and 86.9% (93/107), respectively. PD-L1 and APE1 positive expressions were significantly associated with depth of invasion, lymph node metastasis, pathological type, overall survival, and higher T stage. Furthermore, the expression of PD-L1 in highly differentiated gastric cancers was higher than that in poorly differentiated cancers (P=0.008). Moreover, the expression of APE1 and PD-L1 in gastric cancers was positively correlated (r=0.336, P<0.01). Multivariate analysis showed that the depth of invasion was a significant prognostic factor (risk ratio 19.91; P=0.000), but there was no significant relationship with PD-L1, APE1, prognosis, and other characteristics. Conclusion The deregulation of PD-L1 and APE1 might contribute to the development and the poor prognosis of gastric cancer. Our findings suggest that high expression of PD-L1 and APE1 is a risk factor of gastric cancer and a new biomarker to predict the prognosis of gastric cancer. Furthermore, our findings suggest that targeting the PD-L1 and APE1 signaling pathways may be a new strategy for cancer immune therapy and targeted therapy for gastric cancer, especially in patients with deep invasion and lymph node metastasis. PMID:25733810

  6. Induction of base excision repair enzymes NTH1 and APE1 in rat spleen following aniline exposure

    PubMed Central

    Ma, Huaxian; Wang, Jianling; Abdel-Rahman, Sherif Z.; Boor, Paul J.; Khan, M. Firoze

    2013-01-01

    Mechanisms by which aniline exposure elicits splenotoxicity, especially a tumorigenic response, are not well-understood. Earlier, we have shown that aniline exposure leads to oxidative DNA damage and up-regulation of OGG1 and NEIL1/2 DNA glycosylases in rat spleen. However, the contribution of endonuclease III homolog 1 (NTH1) and apurinic/apyrimidinic endonuclease 1 (APE1) in the repair of aniline-induced oxidative DNA damage in the spleen is not known. This study was, therefore, focused on examining whether NTH1 and APE1 contribute to the repair of oxidative DNA lesions in the spleen, in an experimental condition preceding tumorigenesis. To achieve this, male SD rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. By quantitating the cleavage products, the activities of NTH1 and APE1 were assayed using substrates containing thymine glycol (Tg) and tetrahydrofuran, respectively. Aniline treatment led to significant increases in NTH1- and APE1-mediated BER activity in the nuclear extracts of spleen of aniline-treated rats compared to the controls. NTH1 and APE1 mRNA expression in the spleen showed 2.9- and 3.2-fold increases, respectively, in aniline-treated rats compared to controls. Likewise, Western blot analysis showed that protein expression of NTH1 and APE1 in the nuclear extracts of spleen from aniline-treated rats was 1.9- and 2.7-fold higher than controls, respectively. Immunohistochemistry indicated that aniline treatment also led to stronger immunoreactivity for both NTH1 and APE1 in the spleens, confined to the red pulp areas. These results, thus, show that aniline exposure is associated with induction of NTH1 and APE1 in the spleen. The increased repair activity of NTH1 and APE1 could be an important mechanism for the removal of oxidative DNA lesions. These findings thus identify a novel mechanism through which NTH1 and APE1 may regulate the repair of oxidative DNA

  7. Reconsidering great ape imitation and pantomime. Comment on "Towards a Computational Comparative Neuroprimatology: framing the language-ready brain" by Michael A. Arbib

    NASA Astrophysics Data System (ADS)

    Russon, Anne E.

    2016-03-01

    Like previous commentators, I see Arbib's reconstruction of the mirror neuron system's contribution to language evolution [1] as valuable but in need of revision [2,3]. My concerns focus on his proposed behavioral pathway to language - complex imitation to pantomime to protosign - as it concerns great apes. Arbib portrays these abilities as unique to the human lineage, despite evidence that great apes are capable of all three. I suggest great ape findings worth reconsidering.

  8. African great apes are naturally infected with roseoloviruses closely related to human herpesvirus 7.

    PubMed

    Lavergne, Anne; Donato, Damien; Gessain, Antoine; Niphuis, Henk; Nerrienet, Eric; Verschoor, Ernst J; Lacoste, Vincent

    2014-11-01

    Primates are naturally infected with herpesviruses. During the last 15 years, the search for homologues of human herpesviruses in nonhuman primates allowed the identification of numerous viruses belonging to the different herpesvirus subfamilies and genera. No simian homologue of human herpesvirus 7 (HHV7) has been reported to date. To investigate the putative existence of HHV7-like viruses in African great apes, we applied the consensus-degenerate hybrid oligonucleotide primers (CODEHOP) program-mediated PCR strategy to blood DNA samples from the four common chimpanzee subspecies (Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii), pygmy chimpanzees (Pan paniscus), as well as lowland gorillas (Gorilla gorilla gorilla). This study led to the discovery of a novel roseolovirus close to HHV7 in each of these nonhuman primate species and subspecies. Generation of the partial glycoprotein B (1,111-bp) and full-length DNA polymerase (3,036/3,042-bp) gene sequences allowed the deciphering of their evolutionary relationships. Phylogenetic analyses revealed that HHV7 and its African great ape homologues formed well-supported monophyletic lineages whose topological resemblance to the host phylogeny is suggestive of virus-host codivergence. Notably, the evolutionary branching points that separate HHV7 from African great ape herpesvirus 7 are remarkably congruent with the dates of divergence of their hosts. Our study shows that African great apes are hosts of human herpesvirus homologues, including HHV7 homologues, and that the latter, like other DNA viruses that establish persistent infections, have cospeciated with their hosts. Human herpesviruses are known to possess simian homologues. However, surprisingly, none has been identified to date for human herpesvirus 7 (HHV7). This study is the first to describe simian homologues of HHV7. The extensive search performed on almost all African great ape species and subspecies, i.e., common

  9. GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated measures study

    PubMed Central

    Breton, Carrie V; Kile, Molly L; Catalano, Paul J; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Christiani, David C

    2007-01-01

    Background Chronic arsenic exposure is associated with an increased risk of skin, bladder and lung cancers. Generation of oxidative stress may contribute to arsenic carcinogenesis. Methods To investigate the association between arsenic exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was evaluated in a cohort of 97 women recruited from an arsenic-endemic region of Bangladesh in 2003. Arsenic exposure was measured in urine, toenails, and drinking water. Drinking water and urine samples were collected on three consecutive days. Susceptibility to oxidative stress was evaluated by genotyping relevant polymorphisms in glutathione-s transferase mu (GSTM1), human 8-oxoguanine glycosylase (hOGG1) and apurinic/apyrimidinic endonuclease (APE1) genes using the Taqman method. Data were analyzed using random effects Tobit regression to account for repeated measures and 8-OHdG values below the detection limit. Results A consistent negative effect for APE1 was observed across water, toenail and urinary arsenic models. APE1 148 glu/glu + asp/glu genotype was associated with a decrease in logged 8-OHdG of 0.40 (95%CI -0.73, -0.07) compared to APE1 148 asp/asp. An association between total urinary arsenic and 8-OHdG was observed among women with the GSTM1 null genotype but not in women with GSTM1 positive. Among women with GSTM1 null, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in a 0.84 increase (95% CI 0.27, 1.42), a 0.98 increase (95% CI 033, 1.66) and a 0.85 increase (95% CI 0.27, 1.44) in logged 8-OHdG, respectively. No effects between 8-OHdG and toenail arsenic or drinking water arsenic were observed. Conclusion These results suggest the APE1 variant genotype decreases repair of 8-OHdG and that arsenic exposure is associated with oxidative stress in women who lack a functional GSTM1 detoxification enzyme. PMID:18053222

  10. Gravity and solidity in four great ape species (Gorilla gorilla, Pongo pygmaeus, Pan troglodytes, Pan paniscus): vertical and horizontal variations of the table task.

    PubMed

    Cacchione, Trix; Call, Josep; Zingg, Robert

    2009-05-01

    Three experiments modeled after infant studies were run on four great ape species (Gorilla gorilla, Pongo pygmaeus, Pan troglodytes, Pan paniscus) to investigate their reasoning about solidity and gravity constraints. The aims were: (a) to find out if great apes are subject to gravity biased search or display sensitivity for object solidity, (b) to check for species differences, and (c) to assess if a gravity hypothesis or more parsimonious explanations best account for failures observed. Results indicate that great apes, unlike monkeys, show no reliable gravity bias, that ape species slightly differ in terms of their performance, and that the errors made are best explained by a gravity account.

  11. Apurinic/apyrimidinic endonuclease1/redox factor-1 (Ape1/Ref-1) is essential for IL-21-induced signal transduction through ERK1/2 pathway

    SciTech Connect

    Juliana, Farha M.; Nara, Hidetoshi; Onoda, Tadashi; Rahman, Mizanur; Araki, Akemi; Jin, Lianjin; Fujii, Hodaka; Tanaka, Nobuyuki; Hoshino, Tomoaki; Asao, Hironobu

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer IL-21 induces nuclear accumulation of Ape1/Ref-1 protein. Black-Right-Pointing-Pointer Ape1/Ref-1 is indispensable in IL-21-induced cell proliferation and survival signal. Black-Right-Pointing-Pointer Ape1/Ref-1 is required for IL-21-induced ERK1/2 activation. -- Abstract: IL-21 is a pleiotropic cytokine that regulates T-cell and B-cell differentiation, NK-cell activation, and dendritic cell functions. IL-21 activates the JAK-STAT, ERK, and PI3K pathways. We report here that Ape1/Ref-1 has an essential role in IL-21-induced cell growth signal transduction. Overexpression of Ape1/Ref-1 enhances IL-21-induced cell proliferation, but it is suppressed by overexpressing an N-terminal deletion mutant of Ape1/Ref-1 that lacks the redox domain. Furthermore, knockdown of the Ape1/Ref-1 mRNA dramatically compromises IL-21-induced ERK1/2 activation and cell proliferation with increasing cell death. These impaired activities are recovered by the re-expression of Ape1/Ref-1 in the knockdown cells. Our findings are the first demonstration that Ape1/Ref-1 is an indispensable molecule for the IL-21-mediated signal transduction through ERK1/2 activation.

  12. APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans.

    PubMed

    Zhang, Shi-Heng; Wang, Lin-Ang; Li, Zheng; Peng, Yu; Cun, Yan-Ping; Dai, Nan; Cheng, Yi; Xiao, He; Xiong, Yan-Li; Wang, Dong

    2014-07-14

    To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population. Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ(2) tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility. The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m(2) (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter

  13. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions.

    PubMed

    Watkins, Paul A; Moser, Ann B; Toomer, Cicely B; Steinberg, Steven J; Moser, Hugo W; Karaman, Mazen W; Ramaswamy, Krishna; Siegmund, Kimberly D; Lee, D Rick; Ely, John J; Ryder, Oliver A; Hacia, Joseph G

    2010-10-08

    It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.

  14. Secreted APE1/Ref-1 inhibits TNF-α-stimulated endothelial inflammation via thiol-disulfide exchange in TNF receptor.

    PubMed

    Park, Myoung Soo; Choi, Sunga; Lee, Yu Ran; Joo, Hee Kyoung; Kang, Gun; Kim, Cuk-Seong; Kim, Soo Jin; Lee, Sang Do; Jeon, Byeong Hwa

    2016-03-11

    Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) is a multifunctional protein with redox activity and is proved to be secreted from stimulated cells. The aim of this study was to evaluate the functions of extracellular APE1/Ref-1 with respect to leading anti-inflammatory signaling in TNF-α-stimulated endothelial cells in response to acetylation. Treatment of TNF-α-stimulated endothelial cells with an inhibitor of deacetylase that causes intracellular acetylation, considerably suppressed vascular cell adhesion molecule-1 (VCAM-1). During TSA-mediated acetylation in culture, a time-dependent increase in secreted APE1/Ref-1 was confirmed. The acetyl moiety of acetylated-APE1/Ref-1 was rapidly removed based on the removal kinetics. Additionally, recombinant human (rh) APE1/Ref-1 with reducing activity induced a conformational change in rh TNF-α receptor 1 (TNFR1) by thiol-disulfide exchange. Following treatment with the neutralizing anti-APE1/Ref-1 antibody, inflammatory signals via the binding of TNF-α to TNFR1 were remarkably recovered, leading to up-regulation of reactive oxygen species generation and VCAM-1, in accordance with the activation of p66(shc) and p38 MAPK. These results strongly indicate that anti-inflammatory effects in TNF-α-stimulated endothelial cells by acetylation are tightly linked to secreted APE1/Ref-1, which inhibits TNF-α binding to TNFR1 by reductive conformational change, with suggestion as an endogenous inhibitor of vascular inflammation.

  15. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

    PubMed Central

    2010-01-01

    Background It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems. PMID:20932325

  16. The redox function of APE1 is involved in the differentiation process of stem cells toward a neuronal cell fate.

    PubMed

    Domenis, Rossana; Bergamin, Natascha; Gianfranceschi, Giuseppe; Vascotto, Carlo; Romanello, Milena; Rigo, Silvia; Vagnarelli, Giovanna; Faggiani, Massimo; Parodi, Piercamillo; Kelley, Mark R; Beltrami, Carlo Alberto; Cesselli, Daniela; Tell, Gianluca; Beltrami, Antonio Paolo

    2014-01-01

    Low-to-moderate levels of reactive oxygen species (ROS) govern different steps of neurogenesis via molecular pathways that have been decrypted only partially. Although it has been postulated that redox-sensitive molecules are involved in neuronal differentiation, the molecular bases for this process have not been elucidated yet. The aim of this work was therefore to study the role played by the redox-sensitive, multifunctional protein APE1/Ref-1 (APE1) in the differentiation process of human adipose tissue-derived multipotent adult stem cells (hAT-MASC) and embryonic carcinoma stem cells (EC) towards a neuronal phenotype. Applying a definite protocol, hAT-MASC can adopt a neural fate. During this maturation process, differentiating cells significantly increase their intracellular Reactive Oxygen Species (ROS) levels and increase the APE1 nuclear fraction bound to chromatin. This latter event is paralleled by the increase of nuclear NF-κB, a transcription factor regulated by APE1 in a redox-dependent fashion. Importantly, the addition of the antioxidant N-acetyl cysteine (NAC) to the differentiation medium partially prevents the nuclear accumulation of APE1, increasing the neuronal differentiation of hAT-MASC. To investigate the involvement of APE1 in the differentiation process, we employed E3330, a specific inhibitor of the APE1 redox function. The addition of E3330, either to the neurogenic embryonic carcinoma cell line NT2-D1or to hAT-MASC, increases the differentiation of stem cells towards a neural phenotype, biasing the differentiation towards specific subtypes, such as dopaminergic cells. In conclusion, during the differentiation process of stem cells towards a neuroectodermic phenotype, APE1 is recruited, in a ROS-dependent manner, to the chromatin. This event is associated with an inhibitory effect of APE1 on neurogenesis that may be reversed by E3330. Therefore, E3330 may be employed both to boost neural differentiation and to bias the differentiation

  17. Eye tracking uncovered great apes' ability to anticipate that other individuals will act according to false beliefs.

    PubMed

    Kano, Fumihiro; Krupenye, Christopher; Hirata, Satoshi; Call, Josep

    2017-01-01

    Using a novel eye-tracking test, we recently showed that great apes anticipate that other individuals will act according to false beliefs. This finding suggests that, like humans, great apes understand others' false beliefs, at least in an implicit way. One key question raised by our study is why apes have passed our tests but not previous ones. In this article, we consider this question by detailing the development of our task. We considered 3 major differences in our task compared with the previous ones. First, we monitored apes' eye movements, and specifically their anticipatory looks, to measure their predictions about how agents will behave. Second, we adapted our design from an anticipatory-looking false belief test originally developed for human infants. Third, we developed novel test scenarios that were specifically designed to capture the attention of our ape participants. We then discuss how each difference may help explain differences in performance on our task and previous ones, and finally propose some directions for future studies.

  18. Reaching around barriers: the performance of the great apes and 3-5-year-old children.

    PubMed

    Vlamings, Petra H J M; Hare, Brian; Call, Josep

    2010-03-01

    Inhibitory control has been suggested as a key predictive measure of problem-solving skills in human and nonhuman animals. However, there has yet to be a direct comparison of the inhibitory skills of the nonhuman apes and their development in human children. We compared the inhibitory skills of all great ape species, including 3-5-year-old children in a detour-reaching task, which required subjects to avoid reaching directly for food and instead use an indirect reaching method to successfully obtain the food. We tested 22 chimpanzees, 18 bonobos, 18 orangutans, 6 gorillas and 42 children. Our sample included chimpanzees, bonobos and orangutans housed in zoos (N = 27) and others housed in sanctuaries in their native habitats (N = 37). Overall, orangutans were the most skilful apes, including human children. As expected older children outperformed younger children. Sanctuary chimpanzees and bonobos outperformed their zoo counterparts whereas there was no difference between the two orangutan samples. Most zoo chimpanzees and bonobos failed to solve the original task, but improved their performance with additional training, although the training method determined to a considerable extent the level of success that the apes achieved in a transfer phase. In general, the performance of the older children was far from perfect and comparable to some of the nonhuman apes tested.

  19. Processing of abasic site damaged lesions by APE1 enzyme on DNA adsorbed over normal and organomodified clay.

    PubMed

    Kumari, Bhavini; Banerjee, Shib Shankar; Singh, Vandana; Das, Prolay; Bhowmick, Anil K

    2014-10-01

    The efficiency of the apurinic/apyrimidinic endonuclease (APE1) DNA repair enzyme in the processing of abasic site DNA damage lesions at precise location in DNA oligomer duplexes that are adsorbed on clay surfaces was evaluated. Three different forms of clay namely montmorillonite, quaternary ammonium salt modified montmorillonite and its boiled counterpart i.e. partially devoid of organic moiety were used for a comparative study of adsorption, desorption and DNA repair efficiency on their surfaces. The interaction between the DNA and the clay was analysed by X-ray diffraction, Atomic force microscopy, UV-Vis spectroscopy and Infrared spectroscopy. The abasic site cleavage efficiency of APE1 enzyme was quantitatively evaluated by polyacrylamide gel electrophoresis. Apart from the difference in the DNA adsorption or desorption capacity of the various forms of clay, substantial variation in the repair efficiency of abasic sites initiated by the APE1 enzyme on the clay surfaces was observed. The incision efficiency of APE1 enzyme at abasic sites was found to be greatly diminished, when the DNA was adsorbed over organomodified montmorillonite. The reduced repair activity indicates an important role of the pendant surfactant groups on the clay surfaces in directing APE1 mediated cleavage of abasic site DNA damage lesions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements

    PubMed Central

    Antoniali, Giulia; Lirussi, Lisa; D'Ambrosio, Chiara; Dal Piaz, Fabrizio; Vascotto, Carlo; Casarano, Elena; Marasco, Daniela; Scaloni, Andrea; Fogolari, Federico; Tell, Gianluca

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein contributing to genome stability via repair of DNA lesions via the base excision repair pathway. It also plays a role in gene expression regulation and RNA metabolism. Another, poorly characterized function is its ability to bind to negative calcium responsive elements (nCaRE) of some gene promoters. The presence of many functional nCaRE sequences regulating gene transcription can be envisioned, given their conservation within ALU repeats. To look for functional nCaRE sequences within the human genome, we performed bioinformatic analyses and identified 57 genes potentially regulated by APE1. We focused on sirtuin-1 (SIRT1) deacetylase due to its involvement in cell stress, including senescence, apoptosis, and tumorigenesis, and its role in the deacetylation of APE1 after genotoxic stress. The human SIRT1 promoter presents two nCaRE elements stably bound by APE1 through its N-terminus. We demonstrate that APE1 is part of a multiprotein complex including hOGG1, Ku70, and RNA Pol II, which is recruited on SIRT1 promoter to regulate SIRT1 gene functions during early response to oxidative stress. These findings provide new insights into the role of nCaRE sequences in the transcriptional regulation of mammalian genes. PMID:24356447

  1. Eye tracking uncovered great apes' ability to anticipate that other individuals will act according to false beliefs

    PubMed Central

    Kano, Fumihiro; Krupenye, Christopher; Hirata, Satoshi; Call, Josep

    2017-01-01

    ABSTRACT Using a novel eye-tracking test, we recently showed that great apes anticipate that other individuals will act according to false beliefs. This finding suggests that, like humans, great apes understand others' false beliefs, at least in an implicit way. One key question raised by our study is why apes have passed our tests but not previous ones. In this article, we consider this question by detailing the development of our task. We considered 3 major differences in our task compared with the previous ones. First, we monitored apes' eye movements, and specifically their anticipatory looks, to measure their predictions about how agents will behave. Second, we adapted our design from an anticipatory-looking false belief test originally developed for human infants. Third, we developed novel test scenarios that were specifically designed to capture the attention of our ape participants. We then discuss how each difference may help explain differences in performance on our task and previous ones, and finally propose some directions for future studies. PMID:28451059

  2. Metacarpal torsion in apes, humans, and early Australopithecus: implications for manipulatory abilities.

    PubMed

    Drapeau, Michelle S M

    2015-01-01

    Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown that Australopithecus afarensis and Au. africanus display some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals of Au. afarensis are very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon. Au. africanus present a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than in Au. afarensis. Overall, this study supports previous studies on Au. afarensis and Au. africanus that these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predated Homo.

  3. Identification and Characterization of Inhibitors of Human Apurinic/apyrimidinic Endonuclease APE1

    PubMed Central

    Simeonov, Anton; Kulkarni, Avanti; Dorjsuren, Dorjbal; Jadhav, Ajit; Shen, Min; McNeill, Daniel R.; Austin, Christopher P.; Wilson, David M.

    2009-01-01

    APE1 is the major nuclease for excising abasic (AP) sites and particular 3′-obstructive termini from DNA, and is an integral participant in the base excision repair (BER) pathway. BER capacity plays a prominent role in dictating responsiveness to agents that generate oxidative or alkylation DNA damage, as well as certain chain-terminating nucleoside analogs and 5-fluorouracil. We describe within the development of a robust, 1536-well automated screening assay that employs a deoxyoligonucleotide substrate operating in the red-shifted fluorescence spectral region to identify APE1 endonuclease inhibitors. This AP site incision assay was used in a titration-based high-throughput screen of the Library of Pharmacologically Active Compounds (LOPAC1280), a collection of well-characterized, drug-like molecules representing all major target classes. Prioritized hits were authenticated and characterized via two high-throughput screening assays – a Thiazole Orange fluorophore-DNA displacement test and an E. coli endonuclease IV counterscreen – and a conventional, gel-based radiotracer incision assay. The top, validated compounds, i.e. 6-hydroxy-DL-DOPA, Reactive Blue 2 and myricetin, were shown to inhibit AP site cleavage activity of whole cell protein extracts from HEK 293T and HeLa cell lines, and to enhance the cytotoxic and genotoxic potency of the alkylating agent methylmethane sulfonate. The studies herein report on the identification of novel, small molecule APE1-targeted bioactive inhibitor probes, which represent initial chemotypes towards the development of potential pharmaceuticals. PMID:19484131

  4. Keeping track of time: evidence for episodic-like memory in great apes.

    PubMed

    Martin-Ordas, Gema; Haun, Daniel; Colmenares, Fernando; Call, Josep

    2010-03-01

    Episodic memory, as defined by Tulving, can be described in terms of behavioural elements (what, where and when information) but it is also accompanied by an awareness of one's past (chronesthesia) and a subjective conscious experience (autonoetic awareness). Recent experiments have shown that corvids and rodents recall the where, what and when of an event. This capability has been called episodic-like memory because it only fulfils the behavioural criteria for episodic memory. We tested seven chimpanzees, three orangutans and two bonobos of various ages by adapting two paradigms, originally developed by Clayton and colleagues to test scrub jays. In Experiment 1, subjects were fed preferred but perishable food (frozen juice) and less preferred but non-perishable food (grape). After the food items were hidden, subjects could choose one of them either after 5 min or 1 h. The frozen juice was still available after 5 min but melted after 1 h and became unobtainable. Apes chose the frozen juice significantly more after 5 min and the grape after 1 h. In Experiment 2, subjects faced two baiting events happening at different times, yet they formed an integrated memory for the location and time of the baiting event for particular food items. We also included a memory task that required no temporal encoding. Our results showed that apes remember in an integrated fashion what, where and when (i.e., how long ago) an event happened; that is, apes distinguished between different events in which the same food items were hidden in different places at different times. The temporal control of their choices was not dependent on the familiarity of the platforms where the food was hidden. Chimpanzees' and bonobos' performance in the temporal encoding task was age-dependent, following an inverted U-shaped distribution. The age had no effect on the performance of the subjects in the task that required no temporal encoding.

  5. Old world monkeys compare to apes in the primate cognition test battery.

    PubMed

    Schmitt, Vanessa; Pankau, Birte; Fischer, Julia

    2012-01-01

    Understanding the evolution of intelligence rests on comparative analyses of brain sizes as well as the assessment of cognitive skills of different species in relation to potential selective pressures such as environmental conditions and social organization. Because of the strong interest in human cognition, much previous work has focused on the comparison of the cognitive skills of human toddlers to those of our closest living relatives, i.e. apes. Such analyses revealed that apes and children have relatively similar competencies in the physical domain, while human children excel in the socio-cognitive domain; in particular in terms of attention sharing, cooperation, and mental state attribution. To develop a full understanding of the evolutionary dynamics of primate intelligence, however, comparative data for monkeys are needed. We tested 18 Old World monkeys (long-tailed macaques and olive baboons) in the so-called Primate Cognition Test Battery (PCTB) (Herrmann et al. 2007, Science). Surprisingly, our tests revealed largely comparable results between Old World monkeys and the Great apes. Single comparisons showed that chimpanzees performed only better than the macaques in experiments on spatial understanding and tool use, but in none of the socio-cognitive tasks. These results question the clear-cut relationship between cognitive performance and brain size and--prima facie--support the view of an accelerated evolution of social intelligence in humans. One limitation, however, is that the initial experiments were devised to tap into human specific skills in the first place, thus potentially underestimating both true nonhuman primate competencies as well as species differences.

  6. Metacarpal torsion in apes, humans, and early Australopithecus: implications for manipulatory abilities

    PubMed Central

    2015-01-01

    Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown that Australopithecus afarensis and Au. africanus display some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals of Au. afarensis are very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon. Au. africanus present a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than in Au. afarensis. Overall, this study supports previous studies on Au. afarensis and Au. africanus that these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predated Homo. PMID:26500820

  7. Enamel biorhythms of humans and great apes: the Havers-Halberg Oscillation hypothesis reconsidered.

    PubMed

    Mahoney, Patrick; Miszkiewicz, Justyna J; Pitfield, Rosie; Deter, Chris; Guatelli-Steinberg, Debbie

    2017-02-01

    The Havers-Halberg Oscillation (HHO) hypothesis links evidence for the timing of a biorhythm retained in permanent tooth enamel (Retzius periodicity) to adult body mass and life history traits across mammals. Potentially, these links provide a way to access life history of fossil species from teeth. Recently we assessed intra-specific predictions of the HHO on human children. We reported Retzius periodicity (RP) corresponded with enamel thickness, and cusp formation time, when calculated from isolated deciduous teeth. We proposed the biorhythm might not remain constant within an individual. Here, we test our findings. RP is compared between deciduous second and permanent first molars within the maxillae of four human children. Following this, we report the first RPs for deciduous teeth from modern great apes (n = 4), and compare these with new data for permanent teeth (n = 18) from these species, as well as with previously published values. We also explore RP in teeth that retain hypoplastic defects. Results show RP changed within the maxilla of each child, from thinner to thicker enameled molars, and from one side of a hypoplastic defect to the other. When considered alongside correlations between RP and cusp formation time, these observations provide further evidence that RP is associated with enamel growth processes and does not always remain constant within an individual. RP of 5 days for great ape deciduous teeth lay below the lowermost range of those from permanent teeth of modern orangutan and gorilla, and within the lowermost range of RPs from chimpanzee permanent teeth. Our data suggest associations between RP and enamel growth processes of humans might extend to great apes. These findings provide a new framework from which to develop the HHO hypothesis, which can incorporate enamel growth along with other physiological systems. Applications of the HHO to fossil teeth should avoid transferring RP between deciduous and permanent enamel, or including

  8. Great ape skeletal collections: making the most of scarce and irreplaceable resources in the digital age.

    PubMed

    Gordon, Adam D; Marcus, Emily; Wood, Bernard

    2013-12-01

    Information about primate genomes has re-emphasized the importance of the great apes (Pan, Gorilla, and Pongo) as, for most purposes, the appropriate comparators when generating hypotheses about the most recent common ancestor of the hominins and panins, or the most recent common ancestor of the hominin clade. Great ape skeletal collections are thus an important and irreplaceable resource for researchers conducting these types of comparative analyses, yet the integrity of these collections is threatened by unnecessary use and their availability is threatened by financial pressures on the institutions in which the collections reside. We discuss the general history of great ape skeletal collections, and in order to get a better sense of the utility and potential of these important sources of data we assemble the equivalent of a biography of the Powell-Cotton Collection. We explore the history of how this collection of chimpanzee and gorilla skeletons was accumulated, how it came to be recognized as a potentially important source of comparative information, who has made use of it, and what types of data have been collected. We present a protocol for collecting information about each individual animal (e.g., which bones are preserved, their condition, etc.) and have made that information about the Powell-Cotton Collection freely available in an online relational database (Human Origins Database, www.humanoriginsdatabase.org). As an illustration of the practical application of these data, we developed a tabular summary of ontogenetic information about each individual (see Appendices A and B). Collections like the Powell-Cotton are irreplaceable sources of material regarding the hard-tissue evidence and recent history of the closest living relatives of modern humans. We end this contribution by suggesting ways that curators and the researchers who use and rely on these reference collections could work together to help preserve and protect them so that future generations

  9. Scapular shape of extant hominoids and the African ape/modern human last common ancestor.

    PubMed

    Green, David J; Spiewak, Ted A; Seitelman, Brielle; Gunz, Philipp

    2016-05-01

    Newly discovered early hominin fossil scapulae have bolstered investigations of scapular shape, which have long been used to interpret behavioral variation among primates. However, unexpected similarities between Pongo and Homo - particularly in scapular spine orientation - have raised questions about the functional utility of scapular morphology and its phylogenetic context in the hominin lineage. Not surprisingly, significant disagreement surrounds disparate morphological reconstructions of the modern human/African ape last common ancestor (LCA). Our study utilizes geometric morphometric (GM) approaches - two employing homologous, anatomical landmarks and a "spine-free" alternative using 98 sliding semilandmarks along the boundary of the subscapular fossa. The landmark-based "wireframe" GM analysis principally sorted groups by spine orientation: Homo and Pongo were similar to one another with more transversely-oriented spines as compared to Hylobates and the African apes. In contrast, Homo and Gorilla clustered together in our semilandmark analysis with superoinferiorly broad blades. Pan scapulae were similar, but had more mediolaterally compressed blades and laterally-positioned superior angles. Hylobates was superoinferiorly narrow, yet obliquely expanded relative to the vertebral border. Pongo scapulae were unique among hominoids in being nearly as broad as they were long. Previously documented 'convergence' of Homo and Pongo scapulae appears to be principally driven by similarities in spine orientation, rather than overall blade shape. Therefore, we contend that it is more parsimonious to reconstruct the African ape/Homo LCA scapula as being Gorilla-like, especially in light of similar characterizations of certain fossil hominin scapulae. Accordingly, the evolution of Pan (highly oblique spine and laterally-situated superior angle) and Homo (transversely-oriented spine) scapular morphology would have involved relatively minor shifts from this ancestral

  10. N-Body Classical Systems and Neural Networks on a 3d SIMD Massive Parallel Processor:. APE100/QUADRICS

    NASA Astrophysics Data System (ADS)

    Paolucci, P. S.

    A number of physical systems (e.g., N body Newtonian, Coulombian or Lennard-Jones systems) can be described by N2 interaction terms. Completely connected neural networks are characterised by the same kind of connections: Each neuron sends signals to all the other neurons via synapses. The APE100/Quadricsmassive parallel architecture, with processing power in excess of 100 Gigaflops and a central memory of 8 Gigabytes seems to have processing power and memory adequate to simulate systems formed by more than 1 billion synapses or interaction terms. On the other hand the processing nodes of APE100/Quadrics are organised in a tridimensional cubic lattice; each processing node has a direct communication path only toward the first neighboring nodes. Here we describe a convenient way to map systems with global connectivity onto the first-neighbors connectivity of the APE100/Quadrics architecture. Some numeric criteria, which are useful for matching SIMD tridimensional architectures with globally connected simulations, are introduced.

  11. Hand preferences for coordinated bimanual actions in 777 great apes: implications for the evolution of handedness in hominins.

    PubMed

    Hopkins, William D; Phillips, Kimberley A; Bania, Amanda; Calcutt, Sarah E; Gardner, Molly; Russell, Jamie; Schaeffer, Jennifer; Lonsdorf, Elizabeth V; Ross, Stephen R; Schapiro, Steven J

    2011-05-01

    Whether or not nonhuman primates exhibit population-level handedness remains a topic of considerable scientific debate. Here, we examined handedness for coordinated bimanual actions in a sample of 777 great apes including chimpanzees, bonobos, gorillas, and orangutans. We found population-level right-handedness in chimpanzees, bonobos and gorillas, but left-handedness in orangutans. Directional biases in handedness were consistent across independent samples of apes within each genus. We suggest that, contrary to previous claims, population-level handedness is evident in great apes but differs among species as a result of ecological adaptations associated with posture and locomotion. We further suggest that historical views of nonhuman primate handedness have been too anthropocentric, and we advocate for a larger evolutionary framework for the consideration of handedness and other aspects of hemispheric specialization among primates. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo abelii) follow visual trails to locate hidden food.

    PubMed

    Völter, Christoph J; Call, Josep

    2014-05-01

    Whether nonhuman primates understand causal relations beyond mere associations is still a matter of debate. We presented all four species of nonhuman great apes (N = 36) with a choice between 2 opaque, upside down cups after displacing them out of sight from their starting positions. Crucially, 1 of them had left a yogurt trail behind it. Great apes spontaneously used the trail to select the yogurt baited cup. Follow-up experiments demonstrated that chimpanzees distinguished trails based on the temporal order of cause and effect by ignoring trails that were already present before the reward was hidden. Additionally, chimpanzees did not select cups based on the amount of yogurt near them but instead preferred cups that signaled the endpoint of the trail. We conclude that apes' choices reveal sensitivity to a causal relation between cause (reward) and effect (trail) including their temporal order.

  13. Hand Preferences for Coordinated Bimanual Actions in 777 Great Apes: Implications for the Evolution of Handedness in Hominins

    PubMed Central

    Hopkins, William D.; Phillips, Kimberley A.; Bania, Amanda; Calcutt, Sarah E.; Gardner, Molly; Russell, Jamie; Schaeffer, Jennifer; Lonsdorf, Elizabeth V.; Ross, Stephen R.; Schapiro, Steven J.

    2011-01-01

    Whether or not nonhuman primates exhibit population-level handedness remains a topic of considerable scientific debate. Here, we examined handedness for coordinated bimanual actions in a sample of 777 great apes including chimpanzees, bonobos, gorillas, and orangutans. We found population-level right-handedness in chimpanzees, bonobos and gorillas, but left-handedness in orangutans. Directional biases in handedness were consistent across independent samples of apes within each genus. We suggest that, contrary to previous claims, population-level handedness is evident in great apes but differs among species as a result of ecological adaptations associated with posture and locomotion. We further suggest that historical views of nonhuman primate handedness have been too anthropocentric, and we advocate for a larger evolutionary framework for the consideration of handedness and other aspects of hemispheric specialization among primates. PMID:21334723

  14. Comparative psychology and the great apes - Their competence in learning, language, and numbers

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.

    1990-01-01

    An overview of comparative studies conducted for the past three decades is presented. These studies have led to the establishment of the Language Research Center that provides facilities for research into questions of primate behavior and cognition. Several experiments conducted among chimpanzees are discussed and comparative analyses with the lesser apes, monkeys, and humans are offered. Among the primates, brain complexity varies widely and the evidence is strong that encephalization and enhanced brain complexity facilitate the learning of concepts, the transfer of learning to an advantage, and mediational and observational learning.

  15. Femur ontogeny in humans and great apes: heterochronic implications for hominid évolution

    NASA Astrophysics Data System (ADS)

    Tardieu, Christine

    1997-12-01

    Did the first hominids have a short developmental period similar to that of the great apes, or a longer period closer to that of modern humans? Some morphological modifications undergone by the human femur during growth are shown to be excellent markers of different developmental stages. The femur of the first hominids ( Australopithecus afarensis) shows only features of infantile growth, whereas characters of both infantile and adolescent growth are typical of later hominids ( Homo). In the first australopithecines the period of peripubertal growth would have still been short. The prolongation of the adolescent period appears to be a characteristic of Homo.

  16. The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans.

    PubMed

    Allman, John M; Tetreault, Nicole A; Hakeem, Atiya Y; Manaye, Kebreten F; Semendeferi, Katerina; Erwin, Joseph M; Park, Soyoung; Goubert, Virginie; Hof, Patrick R

    2010-06-01

    The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation

  17. Detection of two distinct forms of apoC-I in great apes.

    PubMed

    Puppione, Donald L; Ryan, Christopher M; Bassilian, Sara; Souda, Puneet; Xiao, Xinshu; Ryder, Oliver A; Whitelegge, Julian P

    2010-03-01

    ApoC-I, the smallest of the soluble apolipoproteins, associates with both TG-rich lipoproteins and HDL. Mass spectral analyses of human apoC-I previously had demonstrated that in the circulation there are two forms, either a 57 amino acid protein or a 55 amino acid protein, due to the loss of two amino acids from the N-terminus. In our analyses of the apolipoproteins of the other great apes by mass spectrometry, four forms of apoC-I were detected. Two of these showed a high degree of identity to the mature and truncated forms of human apoC-I. The other two were homologous to the virtual protein and its truncated form that are encoded by a human pseudogene. In humans, the genes for apoC-I and its pseudogene are located on chromosome 19, the pseudogene being 2.5 kb downstream from the apoC-I gene. Based on the similarity between the apoC-I gene and the pseudogene, it has been concluded that the latter arose from the former as a result of gene duplication approximately 35 million years ago. Interestingly, the virtual protein encoded by the pseudogene is acidic, not basic like apoC-I. In the chimpanzee, there also are two genes for apoC-I, the one upstream encodes a basic protein and the downstream gene, rather than being a pseudogene, encodes an acidic protein (P86336). In addition to reporting on the molecular masses of great ape apoC-I, we were able to clearly demonstrate by "Top-down" sequencing that the acidic form arose from a separate gene. In our analyses, we have measured the molecular masses of apoC-I associated with the HDL of the following great apes: bonobo (Pan paniscus), chimpanzee (Pan troglodytes), and the Sumatran orangutan (Pongo abelii). Genomic variations in chromosome 19 among great apes, baboons and macaques as they relate to both genes for apoC-I and the pseudogene are compared and discussed.

  18. Opal phytoliths found on the teeth of the extinct ape Gigantopithecus blacki: implications for paleodietary studies.

    PubMed

    Ciochon, R L; Piperno, D R; Thompson, R G

    1990-10-01

    Identification of opal phytoliths bonded to the enamel surface of the teeth of Gigantopithecus blacki indicates that this extinct ape had a varied diet of grasses and fruits. By using the scanning electron microscope at magnifications of 2000-6000x specific opal phytoliths were observed and photographed on the fossilized teeth of an extinct species. Since opal phytoliths represent the inorganic remains of once-living plant cells, their documentation on the teeth of Gigantopithecus introduces a promising technique for the determination of diet in extinct mammalian species which should find numerous applications in the field of paleoanthropology as well as vertebrate paleontology.

  19. Comparative psychology and the great apes - Their competence in learning, language, and numbers

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.

    1990-01-01

    An overview of comparative studies conducted for the past three decades is presented. These studies have led to the establishment of the Language Research Center that provides facilities for research into questions of primate behavior and cognition. Several experiments conducted among chimpanzees are discussed and comparative analyses with the lesser apes, monkeys, and humans are offered. Among the primates, brain complexity varies widely and the evidence is strong that encephalization and enhanced brain complexity facilitate the learning of concepts, the transfer of learning to an advantage, and mediational and observational learning.

  20. Barking up the wrong ape--australopiths and the quest for chimpanzee characters in hominid fossils.

    PubMed

    Schwartz, Jeffrey H

    2004-01-01

    With the shift during the 1980s from a human-great ape ultimately to an orangutan-(gorilla-(human-chimp)) theory of relatedness, the search for chimpanzee-like features in early hominids intensified. Reconstructions of early hominids became caricatures of chimpanzees, not only in soft tissue features (e.g. the nasal region), but in supposed bony structures (e.g. an anteriorly and especially superiorly protruding a supraorbital torus with a distinct posttoral sulcus behind). In spite of rampant >Panophilia,< actual morphologies of the majority of early hominid specimens are those cited as uniting an orangutan clade. Those specimens that are >chimpanzee-like< are probably not cladistically hominid.

  1. Diverse small molecule inhibitors of human apurinic/apyrimidinic endonuclease APE1 identified from a screen of a large public collection.

    PubMed

    Dorjsuren, Dorjbal; Kim, Daemyung; Vyjayanti, Vaddadi N; Maloney, David J; Jadhav, Ajit; Wilson, David M; Simeonov, Anton

    2012-01-01

    The major human apurinic/apyrimidinic endonuclease APE1 plays a pivotal role in the repair of base damage via participation in the DNA base excision repair (BER) pathway. Increased activity of APE1, often observed in tumor cells, is thought to contribute to resistance to various anticancer drugs, whereas down-regulation of APE1 sensitizes cells to DNA damaging agents. Thus, inhibiting APE1 repair endonuclease function in cancer cells is considered a promising strategy to overcome therapeutic agent resistance. Despite ongoing efforts, inhibitors of APE1 with adequate drug-like properties have yet to be discovered. Using a kinetic fluorescence assay, we conducted a fully-automated high-throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR), as well as additional public collections, with each compound tested as a 7-concentration series in a 4 µL reaction volume. Actives identified from the screen were subjected to a panel of confirmatory and counterscreen tests. Several active molecules were identified that inhibited APE1 in two independent assay formats and exhibited potentiation of the genotoxic effect of methyl methanesulfonate with a concomitant increase in AP sites, a hallmark of intracellular APE1 inhibition; a number of these chemotypes could be good starting points for further medicinal chemistry optimization. To our knowledge, this represents the largest-scale HTS to identify inhibitors of APE1, and provides a key first step in the development of novel agents targeting BER for cancer treatment.

  2. Diverse Small Molecule Inhibitors of Human Apurinic/Apyrimidinic Endonuclease APE1 Identified from a Screen of a Large Public Collection

    PubMed Central

    Dorjsuren, Dorjbal; Kim, Daemyung; Vyjayanti, Vaddadi N.; Maloney, David J.; Jadhav, Ajit; Wilson, David M.; Simeonov, Anton

    2012-01-01

    The major human apurinic/apyrimidinic endonuclease APE1 plays a pivotal role in the repair of base damage via participation in the DNA base excision repair (BER) pathway. Increased activity of APE1, often observed in tumor cells, is thought to contribute to resistance to various anticancer drugs, whereas down-regulation of APE1 sensitizes cells to DNA damaging agents. Thus, inhibiting APE1 repair endonuclease function in cancer cells is considered a promising strategy to overcome therapeutic agent resistance. Despite ongoing efforts, inhibitors of APE1 with adequate drug-like properties have yet to be discovered. Using a kinetic fluorescence assay, we conducted a fully-automated high-throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR), as well as additional public collections, with each compound tested as a 7-concentration series in a 4 µL reaction volume. Actives identified from the screen were subjected to a panel of confirmatory and counterscreen tests. Several active molecules were identified that inhibited APE1 in two independent assay formats and exhibited potentiation of the genotoxic effect of methyl methanesulfonate with a concomitant increase in AP sites, a hallmark of intracellular APE1 inhibition; a number of these chemotypes could be good starting points for further medicinal chemistry optimization. To our knowledge, this represents the largest-scale HTS to identify inhibitors of APE1, and provides a key first step in the development of novel agents targeting BER for cancer treatment. PMID:23110144

  3. Comparing humans and nonhuman great apes in the broken cloth problem: Is their knowledge causal or perceptual?

    PubMed

    Albiach-Serrano, Anna; Sebastián-Enesco, Carla; Seed, Amanda; Colmenares, Fernando; Call, Josep

    2015-11-01

    When presented with the broken cloth problem, both human children and nonhuman great apes prefer to pull a continuous cloth over a discontinuous cloth in order to obtain a desired object resting on top. This has been interpreted as evidence that they preferentially attend to the functionally relevant cues of the task (e.g., presence or absence of a gap along the cloth). However, there is controversy regarding whether great apes' behavior is underpinned by causal knowledge, involving abstract concepts (e.g., support, connection), or by perceptual knowledge, based on percepts (e.g., contact, continuity). We presented chimpanzees, orangutans, and 2-, 3-, and 4-year-old children with two versions of the broken cloth problem. The Real condition, made with paper strips, could be solved based on either perceptual cues or causal knowledge. The Painted condition, which looked very similar, could be solved only by attending to perceptual cues. All groups mastered the Real condition, in line with previous results. Older children (3- and 4-year-olds) performed significantly better in this condition than all other groups, but the performance of apes and children did not differ sharply, with 2-year-olds and apes obtaining similar results. In contrast, only 4-year-olds solved the Painted condition. We propose causal knowledge to explain the general good performance of apes and humans in the Real condition compared with the Painted condition. In addition, we suggest that symbolic knowledge might account for 4-year-olds' performance in the Painted condition. Our findings add to the growing literature supporting the idea that learning from arbitrary cues is not a good explanation for the performance of apes and humans on some kinds of physical task.

  4. Impact of cadmium on hOGG1 and APE1 as a function of the cellular p53 status.

    PubMed

    Hamann, Ingrit; König, Charlotte; Richter, Constanze; Jahnke, Gunnar; Hartwig, Andrea

    2012-08-01

    The tumor suppressor protein p53, often called the guardian of the genome, is involved in important cellular processes, such as cell cycle control, apoptosis and DNA repair. With respect to BER, p53 might physically interact with and affect the transcription of different BER proteins such as hOGG1, APE1 or Polβ. In studies in HCT116 p53(-/-) cells previously published, activity and mRNA expression of hOGG1 were found to be significantly decreased, while down-regulation of APE1 mRNA and protein levels in response to genotoxic stress were only described in HCT116 p53(+/+) cells, but not in the isogenic p53 knockout cell line. The predominantly indirect genotoxic carcinogen cadmium inhibits the BER pathway and potentially interferes with zinc binding proteins such as p53. Therefore, this study was accomplished to investigate whether p53 is involved in the cadmium-induced inhibition of BER activity. To address this issue we applied a non-radioactive cleavage test system based on a Cy5-labeled oligonucleotide. We present evidence that p53 is not essential for hOGG1 and APE1 gene expression as well as OGG and APE activity in unstressed HCT116 cells; however, it plays an important role in the cellular response to cadmium treatment. Here, a direct involvement of p53 was only observed with respect to APE1 gene expression contributing to an altered APE activity, while OGG activity was presumably affected indirectly due to a stronger accumulation of cadmium in HCT116 p53(+/+) cells. In summary, p53 indeed affects the BER pathway directly and indirectly in response to cadmium treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Apurinic/Apyrimidinic Endonuclease/Redox Effector Factor-1(APE/Ref-1): A Unique Target for the Prevention and Treatment of Human Melanoma

    PubMed Central

    Yang, Sun

    2009-01-01

    Abstract Management of melanoma is a growing and challenging public health issue requiring novel and multidisciplinary approaches to achieve more efficient prevention and therapeutic benefits. The aim of this article is to show the critical role of APE/Ref-1 on melanomagenesis and progression. APE/Ref-1 serves as a redox-sensitive node of convergence of various signals as well as a DNA-repair enzyme, and its activation protects melanocytes and melanoma cells from chronic oxidative stress and promotes cell survival via mediation of downstream pathways. APE/Ref-1 is a strong candidate as a potential drug-treatable target for the prevention and treatment of human melanoma. Lead compounds exhibiting inhibitory effects on APE/Ref-1 are also reviewed. We anticipate potential clinical benefit in the future through inhibition of APE/Ref-1 and/or Ref-1-mediated signaling. Antioxid. Redox Signal. 11, 639–650. PMID:18715151

  6. Experimental study enhancing the chemosensitivity of multiple myeloma to melphalan by using a tissue-specific APE1-silencing RNA expression vector.

    PubMed

    Yang, Zhen-Zhou; Chen, Xing-Hua; Wang, Dong

    2007-01-01

    Because of a developing resistance to chemotherapy agents, multiple myeloma (MM) has been an incurable disease until now. As a means to overcome MM tumor cell resistance and/or sensitize tumor cells to chemotherapeutic treatments currently used, we examined the role of human apurinic/apyrimidinic endonuclease 1 (APE1) in resistance and prognosis in patients with MM. Multiple myeloma cells were analyzed by using bone marrow specimens from 32 patients with MM and 10 normal volunteers. The positive rate of APE1 protein expression was 65.6% in the bone marrow specimens of patients with MM with known clinical outcome. Positive rate of APE1 expression beyond grade 2 in the relapsed/refractory group was significantly higher than that in the untreated group. No positive results of grade > 2 were detected in bone marrow specimens from patients with noncancerous disease. It was also confirmed that the amount of APE1 protein in KM3 cells was positively correlated with the dose and action time of melphalan. Because APE1 was overexpressed in refractory/relapsed MM cells, siRNA-targeted technology was used to decrease APE1 levels in KM3 cells, with protein levels deceasing to 80%-90% within 24 hours and continuing to decease for 72 hours. The best dose and time of inhibiting expression of APE1 protein were 3 mug and 2 days long. A decrease in APE1 levels in siRNA-treated KM3 cells led to enhanced cell sensitization to melphalan. The findings herein present prognostic and therapeutic implications for treating relapsed/refractory MM. The APE1-silencing RNA results demonstrate the feasibility of the therapeutic modulation of APE1 using a variety of molecules and approaches.

  7. Transcriptional Up-Regulation of APE1/Ref-1 in Hepatic Tumor: Role in Hepatocytes Resistance to Oxidative Stress and Apoptosis

    PubMed Central

    Di Maso, Vittorio; Mediavilla, María Gabriela; Vascotto, Carlo; Lupo, Francesco; Baccarani, Umberto; Avellini, Claudio; Tell, Gianluca; Tiribelli, Claudio; Crocè, Lory Saveria

    2015-01-01

    Objective Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. Design In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. Results APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. Conclusion APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment. PMID:26624999

  8. 17β-estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia.

    PubMed

    Dietrich, Alicia K; Humphreys, Gwendolyn I; Nardulli, Ann M

    2013-11-01

    While it is well established that 17β-estradiol (E2) protects the rodent brain from ischemia-induced damage, it has been unclear how this neuroprotective effect is mediated. Interestingly, convincing evidence has also demonstrated that maintaining or increasing the expression of the oxidative stress response and DNA repair protein apurinic endonuclease 1 (Ape1) is instrumental in reducing ischemia-induced damage in the brain. Since E2 increases expression of the oxidative stress response proteins Cu/Zn superoxide dismutase and thioredoxin in the brain, we hypothesized that E2 may also increase Ape1 expression and that this E2-induced expression of Ape1 may help to mediate the neuroprotective effects of E2 in the brain. To test this hypothesis, we utilized three model systems including primary cortical neurons, brain slice cultures, and whole animals. Although estrogen receptor α and Ape1 were expressed in primary cortical neurons, E2 did not alter Ape1 expression in these cells. However, immunofluorescent staining and quantitative Western blot analysis demonstrated that estrogen receptor α and Ape1 were expressed in the nuclei of cortical neurons in brain slice cultures and that E2 increased Ape1 expression in the cerebral cortex of these cultures. Furthermore, Ape1 expression was increased and oxidative DNA damage was decreased in the cerebral cortices of ovariectomized female C57Bl/6J mice that had been treated with E2 and exposed to hypoxia. Taken together, our studies demonstrate that the neuronal microenvironment may be required for increased Ape1 expression and that E2 enhances expression of Ape1 and reduces oxidative DNA damage, which may in turn help to reduce ischemia-induced damage in the cerebral cortex and mediate the neuroprotective effects of E2.

  9. Enamel thickness in the Middle Miocene great apes Anoiapithecus, Pierolapithecus and Dryopithecus

    PubMed Central

    Alba, D. M.; Fortuny, J.; Moyà-Solà, S.

    2010-01-01

    On the basis of industrial computed tomography, relative enamel thickness (RET) is computed in three Middle Miocene (ca 11.9–11.8 Ma) hominoids from Abocador de Can Mata (Vallès-Penedès Basin, Catalonia, Spain): Pierolapithecus catalaunicus from BCV1 and Anoiapithecus brevirostris from C3-Aj, interpreted as stem hominids; and Dryopithecus fontani from C3-Ae of uncertain phylogenetic affinities. Pierolapithecus displays an average RET value of 19.5, Anoiapithecus of 18.6 and Dryopithecus of 10.6. The thick-enamelled condition of Pierolapithecus and Anoiapithecus is also characteristic of afropithecids, including the more derived kenyapithecins from the early Middle Miocene of Eurasia (Griphopithecus and Kenyapithecus). Given the presence of other dentognathic and craniofacial similarities, thick enamel may be interpreted as a symplesiomorphy of the Hominidae (the great ape and human clade), which would have been later independently modified along several lineages. Given the correlation between thick enamel and hard-object feeding, our results suggest that thick enamel might have been the fundamental adaptation that enabled the out-of-Africa dispersal of great-ape ancestors and their subsequent initial radiation throughout Eurasia. The much thinner enamel of Dryopithecus is difficult to interpret given phylogenetic uncertainties, being either a hominine synapomorphy or a convergently developed feature. PMID:20335211

  10. Rational versus anti-rational interpretations of science: an ape-language case-study.

    PubMed

    Farrell, Robert P

    2006-03-01

    Robert Nola (2003) has argued that anti-rationalist interpretations of science fail to adequately explain the process of science, since objective reasons can be causal factors in belief formation. While I agree with Nola that objective reasons can be a cause of belief, in this paper I present a version of the strong programme in the sociology of knowledge, the Interests Thesis, and argue that the Interests Thesis provides a plausible explanation of an episode in the history of ape-language research. Specifically, I examine Terrace, Petitto, Sandess, & Bever (1979, 1980) illegitimate comparison of the signing of their chimpanzee, Nim, with data from human early childhood language development, and argue that Terrace et al.'s interests played a causal role in determining their sceptical beliefs concerning ape linguistic abilities. However, I go on to argue that Terrace et al.'s interests are not the only causal factors in determining their beliefs: objective reasons, associated with the institution of new methodologies, were also causally determinative of Terrace et al.'s sceptical beliefs. Consequently, I argue that belief formation in science is a multi-factorial affair wherein both interests and objective reasons have causal roles. I finish the paper with two conjectures concerning the proper locus of scientific rationality.

  11. Common Visual Preference for Curved Contours in Humans and Great Apes

    PubMed Central

    2015-01-01

    Among the visual preferences that guide many everyday activities and decisions, from consumer choices to social judgment, preference for curved over sharp-angled contours is commonly thought to have played an adaptive role throughout human evolution, favoring the avoidance of potentially harmful objects. However, because nonhuman primates also exhibit preferences for certain visual qualities, it is conceivable that humans’ preference for curved contours is grounded on perceptual and cognitive mechanisms shared with extant nonhuman primate species. Here we aimed to determine whether nonhuman great apes and humans share a visual preference for curved over sharp-angled contours using a 2-alternative forced choice experimental paradigm under comparable conditions. Our results revealed that the human group and the great ape group indeed share a common preference for curved over sharp-angled contours, but that they differ in the manner and magnitude with which this preference is expressed behaviorally. These results suggest that humans’ visual preference for curved objects evolved from earlier primate species’ visual preferences, and that during this process it became stronger, but also more susceptible to the influence of higher cognitive processes and preference for other visual features. PMID:26558754

  12. Lithium concentration profiles in APE:LiNbO3 optical waveguides

    NASA Astrophysics Data System (ADS)

    Nekvindova, Pavla; Spirkova-Hradilova, Jarmila; Vacik, Jiri; Cervena, Jarmila; Schroefel, Josef

    1999-12-01

    Lithium concentration depth profiles of proton exchanged (PE) and annealed proton exchanged (APE) lithium niobate optical waveguides were monitored by neutron depth profiling (NDP) for a large variety of the samples. Results of the measurements are related to the corresponding ne depth profiles as measure by the standard prisms coupling method. It was found that cLi depth profiles of the PE waveguides fabricated in X- and Z-cuts using the same fabrication conditions are almost identical indicating thus very similar extend of H+ $ARLR Li+ exchange reaction. The maximal depths of the exchanged layers were 3 micrometers . The following annealing causes a massive transport of lithium atoms towards the exchanged regions of the as- exchanged samples which is differs in the both types of the cuts. The Li-transport in the X-cuts seems to be hampered by a barrier formed by the larger amount of in-diffused interstitial hydrogen in the X-cuts, which results in a more-less step-like profiles of the X-cuts parameters. A formula relating nc to CLi values for the APE waveguides is also presented.

  13. Evidence that the rate of strong selective sweeps increases with population size in the great apes.

    PubMed

    Nam, Kiwoong; Munch, Kasper; Mailund, Thomas; Nater, Alexander; Greminger, Maja Patricia; Krützen, Michael; Marquès-Bonet, Tomàs; Schierup, Mikkel Heide

    2017-02-14

    Quantifying the number of selective sweeps and their combined effects on genomic diversity in humans and other great apes is notoriously difficult. Here we address the question using a comparative approach to contrast diversity patterns according to the distance from genes in all great ape taxa. The extent of diversity reduction near genes compared with the rest of intergenic sequences is greater in a species with larger effective population size. Also, the maximum distance from genes at which the diversity reduction is observed is larger in species with large effective population size. In Sumatran orangutans, the overall genomic diversity is ∼30% smaller than diversity levels far from genes, whereas this reduction is only 9% in humans. We show by simulation that selection against deleterious mutations in the form of background selection is not expected to cause these differences in diversity among species. Instead, selective sweeps caused by positive selection can reduce diversity level more severely in a large population if there is a higher number of selective sweeps per unit time. We discuss what can cause such a correlation, including the possibility that more frequent sweeps in larger populations are due to a shorter waiting time for the right mutations to arise.

  14. APES: Acute Precipitating Electron Spectrometer -- A high time resolution monodirectional magnetic deflection electron spectrometer

    NASA Astrophysics Data System (ADS)

    Michell, R. G.; Samara, M.; Grubbs, G.; Ogasawara, K.; Miller, G.; Trevino, J. A.; Webster, J.; Stange, J.

    2016-06-01

    We present a description of the Acute Precipitating Electron Spectrometer (APES) that was designed and built for the Ground-to-Rocket Electron Electrodynamics Correlative Experiment (GREECE) auroral sounding rocket mission. The purpose was to measure the precipitating electron spectrum with high time resolution, on the order of milliseconds. The trade-off made in order to achieve high time resolution was to limit the aperture to only one look direction. The energy selection was done by using a permanent magnet to separate the incoming electrons, such that the different energies would fall onto different regions of the microchannel plate and therefore be detected by different anodes. A rectangular microchannel plate (MCP) was used (15 mm × 100 mm), and there was a total of 50 discrete anodes under the MCP, each one 15 mm × 1.5 mm, with a 0.5 mm spacing between anodes. The target energy range of APES was 200 eV to 30 keV.

  15. Predicting the Vulnerability of Great Apes to Disease: The Role of Superspreaders and Their Potential Vaccination

    PubMed Central

    Carne, Charlotte; Semple, Stuart; Morrogh-Bernard, Helen; Zuberbühler, Klaus; Lehmann, Julia

    2013-01-01

    Disease is a major concern for the conservation of great apes, and one that is likely to become increasingly relevant as deforestation and the rise of ecotourism bring humans and apes into ever closer proximity. Consequently, it is imperative that preventative measures are explored to ensure that future epidemics do not wipe out the remaining populations of these animals. In this paper, social network analysis was used to investigate vulnerability to disease in a population of wild orang-utans and a community of wild chimpanzees. Potential ‘superspreaders’ of disease - individuals with disproportionately central positions in the community or population - were identified, and the efficacy of vaccinating these individuals assessed using simulations. Three resident female orang-utans were identified as potential superspreaders, and females and unflanged males were predicted to be more influential in disease spread than flanged males. By contrast, no superspreaders were identified in the chimpanzee network, although males were significantly more central than females. In both species, simulating the vaccination of the most central individuals in the network caused a greater reduction in potential disease pathways than removing random individuals, but this effect was considerably more pronounced for orang-utans. This suggests that targeted vaccinations would have a greater impact on reducing disease spread among orang-utans than chimpanzees. Overall, these results have important implications for orang-utan and chimpanzee conservation and highlight the role that certain individuals may play in the spread of disease and its prevention by vaccination. PMID:24386405

  16. Retrospective Serology Study of Respiratory Virus Infections in Captive Great Apes

    PubMed Central

    Buitendijk, Hester; Fagrouch, Zahra; Niphuis, Henk; Bogers, Willy M.; Warren, Kristin S.; Verschoor, Ernst J.

    2014-01-01

    Great apes are extremely sensitive to infections with human respiratory viruses. In this study, we retrospectively analyzed sera from captive chimpanzees, gorillas and orang-utans. More than 1000 sera (403 chimpanzee, 77 gorilla, and 535 orang-utan sera) were analyzed for antibodies to the human respiratory viruses RSV (respiratory syncytial virus, hMPV (human metapneumovirus), H1N1 and H3N2 influenza A viruses, and influenza B virus. In all ape species high seroprevalences were found for RSV, hMPV, and influenza B virus. A high percentage of captive chimpanzees also showed evidence of influenza A H1N1 infections, and had low levels of H3N2 antibodies, while in sera from gorillas and orang-utans antibody levels to influenza A and B viruses were much lower or practically absent. Transmission of respiratory viruses was examined in longitudinal sera of young chimpanzees, and in chimpanzee sera taken during health checks. In young animals isolated cases of influenza infections were monitored, but evidence was found for single introductions followed by a rapid dissemination of RSV and hMPV within the group. Implementation of strict guidelines for handling and housing of nonhuman primates was shown to be an efficient method to reduce the introduction of respiratory infections in colonies of captive animals. RSV seroprevalence rates of chimpanzees remained high, probably due to circulating virus in the chimpanzee colony. PMID:24662675

  17. Are apes inequity averse? New data on the token-exchange paradigm.

    PubMed

    Bräuer, Juliane; Call, Josep; Tomasello, Michael

    2009-02-01

    Recent studies have produced mixed evidence about inequity aversion in nonhuman primates. Brosnan et al. [Proceedings of the Royal Society of London. Series B. Biological Sciences 272:253-258, 2005] found inequity aversion in chimpanzees and argued that effort is crucial, if subjects are to evaluate how they are rewarded in comparison to a competitor for an identical performance. In this study we investigated inequity aversion with chimpanzees, bonobos and orangutans, using the method of Brosnan et al. [Proceedings of the Royal Society of London. Series B. Biological Sciences 272:253-258, 2005] after introducing some methodological improvements. Subjects always received a less-preferred food in exchange for a token, whereas the competitor received either the same type of food for their token (equity) or a more favored food for it (inequity). Apes did not refuse more of the less-preferred food when a competitor had received the more favored food. Thus, with an improved methodology we failed to reproduce the findings of Brosnan et al. [Proceedings of the Royal Society of London. Series B. Biological Sciences 272:253-258, 2005] that apes show inequity aversion. (c) 2008 Wiley-Liss, Inc.

  18. Common Visual Preference for Curved Contours in Humans and Great Apes.

    PubMed

    Munar, Enric; Gómez-Puerto, Gerardo; Call, Josep; Nadal, Marcos

    2015-01-01

    Among the visual preferences that guide many everyday activities and decisions, from consumer choices to social judgment, preference for curved over sharp-angled contours is commonly thought to have played an adaptive role throughout human evolution, favoring the avoidance of potentially harmful objects. However, because nonhuman primates also exhibit preferences for certain visual qualities, it is conceivable that humans' preference for curved contours is grounded on perceptual and cognitive mechanisms shared with extant nonhuman primate species. Here we aimed to determine whether nonhuman great apes and humans share a visual preference for curved over sharp-angled contours using a 2-alternative forced choice experimental paradigm under comparable conditions. Our results revealed that the human group and the great ape group indeed share a common preference for curved over sharp-angled contours, but that they differ in the manner and magnitude with which this preference is expressed behaviorally. These results suggest that humans' visual preference for curved objects evolved from earlier primate species' visual preferences, and that during this process it became stronger, but also more susceptible to the influence of higher cognitive processes and preference for other visual features.

  19. Social organization and the evolution of cumulative technology in apes and hominins.

    PubMed

    Pradhan, Gauri R; Tennie, Claudio; van Schaik, Carel P

    2012-07-01

    Culturally supported accumulation (or ratcheting) of technological complexity is widely seen as characterizing hominin technology relative to that of the extant great apes, and thus as representing a threshold in cultural evolution. To explain this divide, we modeled the process of cultural accumulation of technology, which we defined as adding new actions to existing ones to create new functional combinations, based on a model for great ape tool use. The model shows that intraspecific and interspecific variation in the presence of simple and cumulative technology among extant orangutans and chimpanzees is largely due to variation in sociability, and hence opportunities for social learning. The model also suggests that the adoption of extensive allomaternal care (cooperative breeding) in early Pleistocene Homo, which led to an increase in sociability and to teaching, and hence increased efficiency of social learning, was enough to facilitate technological ratcheting. Hence, socioecological changes, rather than advances in cognitive abilities, can account for the cumulative cultural changes seen until the origin of the Acheulean. The consequent increase in the reliance on technology could have served as the pacemaker for increased cognitive abilities. Our results also suggest that a more important watershed in cultural evolution was the rise of donated culture (technology or concepts), in which technology or concepts was transferred to naïve individuals, allowing them to skip many learning steps, and specialization arose, which allowed individuals to learn only a subset of the population's skills. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Rapid evolution of the cerebellum in humans and other great apes.

    PubMed

    Barton, Robert A; Venditti, Chris

    2014-10-20

    Humans' unique cognitive abilities are usually attributed to a greatly expanded neocortex, which has been described as "the crowning achievement of evolution and the biological substrate of human mental prowess". The human cerebellum, however, contains four times more neurons than the neocortex and is attracting increasing attention for its wide range of cognitive functions. Using a method for detecting evolutionary rate changes along the branches of phylogenetic trees, we show that the cerebellum underwent rapid size increase throughout the evolution of apes, including humans, expanding significantly faster than predicted by the change in neocortex size. As a result, humans and other apes deviated significantly from the general evolutionary trend for neocortex and cerebellum to change in tandem, having significantly larger cerebella relative to neocortex size than other anthropoid primates. These results suggest that cerebellar specialization was a far more important component of human brain evolution than hitherto recognized and that technical intelligence was likely to have been at least as important as social intelligence in human cognitive evolution. Given the role of the cerebellum in sensory-motor control and in learning complex action sequences, cerebellar specialization is likely to have underpinned the evolution of humans' advanced technological capacities, which in turn may have been a preadaptation for language. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Children conform to the behavior of peers; other great apes stick with what they know.

    PubMed

    Haun, Daniel B M; Rekers, Yvonne; Tomasello, Michael

    2014-12-01

    All primates learn things from conspecifics socially, but it is not clear whether they conform to the behavior of these conspecifics--if conformity is defined as overriding individually acquired behavioral tendencies in order to copy peers' behavior. In the current study, chimpanzees, orangutans, and 2-year-old human children individually acquired a problem-solving strategy. They then watched several conspecific peers demonstrate an alternative strategy. The children switched to this new, socially demonstrated strategy in roughly half of all instances, whereas the other two great-ape species almost never adjusted their behavior to the majority's. In a follow-up study, children switched much more when the peer demonstrators were still present than when they were absent, which suggests that their conformity arose at least in part from social motivations. These results demonstrate an important difference between the social learning of humans and great apes, a difference that might help to account for differences in human and nonhuman cultures. © The Author(s) 2014.

  2. Comparative population genomics of the ejaculate in humans and the great apes.

    PubMed

    Good, Jeffrey M; Wiebe, Victor; Albert, Frank W; Burbano, Hernán A; Kircher, Martin; Green, Richard E; Halbwax, Michel; André, Claudine; Atencia, Rebeca; Fischer, Anne; Pääbo, Svante

    2013-04-01

    The rapid molecular evolution of reproductive genes is nearly ubiquitous across animals, yet the selective forces and functional targets underlying this divergence remain poorly understood. Humans and closely related species of great apes show strongly divergent mating systems, providing a powerful system to investigate the influence of sperm competition on the evolution of reproductive genes. This is complemented by detailed information on male reproductive biology and unparalleled genomic resources in humans. Here, we have used custom microarrays to capture and sequence 285 genes encoding proteins present in the ejaculate as well as 101 randomly selected control genes in 21 gorillas, 20 chimpanzees, 20 bonobos, and 20 humans. In total, we have generated >25× average genomic coverage per individual for over 1 million target base pairs. Our analyses indicate high levels of evolutionary constraint across much of the ejaculate combined with more rapid evolution of genes involved in immune defense and proteolysis. We do not find evidence for appreciably more positive selection along the lineage leading to bonobos and chimpanzees, although this would be predicted given more intense sperm competition in these species. Rather, the extent of positive and negative selection depended more on the effective population sizes of the species. Thus, general patterns of male reproductive protein evolution among apes and humans depend strongly on gene function but not on inferred differences in the intensity of sperm competition among extant species.

  3. APES: Acute Precipitating Electron Spectrometer - A High Time Resolution Monodirectional Magnetic Deflection Electron Spectrometer

    NASA Technical Reports Server (NTRS)

    Michell, R. G.; Samara, M.; Grubbs, G., II; Ogasawara, K.; Miller, G.; Trevino, J. A.; Webster, J.; Stange, J.

    2016-01-01

    We present a description of the Acute Precipitating Electron Spectrometer (APES) that was designed and built for the Ground-to-Rocket Electron Electrodynamics Correlative Experiment (GREECE) auroral sounding rocket mission. The purpose was to measure the precipitating electron spectrum with high time resolution, on the order of milliseconds. The trade-off made in order to achieve high time resolution was to limit the aperture to only one look direction. The energy selection was done by using a permanent magnet to separate the incoming electrons, such that the different energies would fall onto different regions of the microchannel plate and therefore be detected by different anodes. A rectangular microchannel plate (MCP) was used (15 mm x 100 mm), and there was a total of 50 discrete anodes under the MCP, each one 15 mm x 1.5 mm, with a 0.5 mm spacing between anodes. The target energy range of APES was 200 eV to 30 keV.

  4. Evidence that the rate of strong selective sweeps increases with population size in the great apes

    PubMed Central

    Nam, Kiwoong; Munch, Kasper; Mailund, Thomas; Nater, Alexander; Greminger, Maja Patricia; Krützen, Michael; Marquès-Bonet, Tomàs; Schierup, Mikkel Heide

    2017-01-01

    Quantifying the number of selective sweeps and their combined effects on genomic diversity in humans and other great apes is notoriously difficult. Here we address the question using a comparative approach to contrast diversity patterns according to the distance from genes in all great ape taxa. The extent of diversity reduction near genes compared with the rest of intergenic sequences is greater in a species with larger effective population size. Also, the maximum distance from genes at which the diversity reduction is observed is larger in species with large effective population size. In Sumatran orangutans, the overall genomic diversity is ∼30% smaller than diversity levels far from genes, whereas this reduction is only 9% in humans. We show by simulation that selection against deleterious mutations in the form of background selection is not expected to cause these differences in diversity among species. Instead, selective sweeps caused by positive selection can reduce diversity level more severely in a large population if there is a higher number of selective sweeps per unit time. We discuss what can cause such a correlation, including the possibility that more frequent sweeps in larger populations are due to a shorter waiting time for the right mutations to arise. PMID:28137852

  5. Recently recovered Kenyapithecus mandible and its implications for great ape and human origins.

    PubMed Central

    McCrossin, M L; Benefit, B R

    1993-01-01

    We report here a Kenyapithecus africanus juvenile mandible recovered from middle Miocene (ca. 14-16 million years) deposits of Maboko Island (Lake Victoria), Kenya. Symphyseal and dental attributes of the mandible distinguish K. africanus, a species widely regarded as the earliest known member of the great ape and human clade, from other Miocene large-bodied hominoids. The Maboko Island mandible exhibits a markedly proclined symphyseal axis, massive inferior transverse torus, mesiodistally narrow, high-crowned, and strongly procumbent lateral incisor, and molars with cingula restricted to the median buccal cleft. Although the presence of some of these conditions in Kenyapithecus was suggested earlier, the fragmentary and ill-preserved nature of previously known specimens led certain authorities to doubt their validity. Our assessment of mandibular and dental morphology indicates that K. africanus diverged after Proconsul and Griphopithecus but prior to the last common ancestor of Sivapithecus, extant great apes, and humans. The robustly constructed mandibular symphysis and anterior dentition suggest that incisal biting played as important a role as thick molar enamel in the dietary adaptations of K. africanus. Images Fig. 1 Fig. 2 PMID:8446615

  6. The choice to access outdoor areas affects the behavior of great apes.

    PubMed

    Kurtycz, Laura M; Wagner, Katherine E; Ross, Stephen R

    2014-01-01

    Outdoor access is often cited as a critical component of appropriate housing for great apes in captivity, and although studies have shown that offering primates choices can improve welfare, choice to access specific areas has been empirically neglected. Behavioral data were collected on chimpanzees and gorillas housed in naturalistic enclosures while (a) restricted to an indoor enclosure and (b) permitted free access to an adjacent outdoor area. To isolate the factor of choice, only the sessions in which apes remained indoors were compared. With choice, chimpanzees showed more frequent social, F(1, 5) = 20.526, p = .006, and self-directed behaviors, F(1, 5) = 13.507, p = .014, and lower inactivity levels, F(1, 5) = 9.239, p = .029. Gorillas were more frequently inactive, F(1, 8) = 22.259, p = .002, and produced lower levels of object manipulation, F(1, 8) = 8.243, p = .021, and feeding, F(1, 8) = 5.407, p = .049. Results are consistent with an association between choice and the expression of species-typical and arousal behaviors in chimpanzees. The effects are less evident in gorillas, but this outcome may be buffered by the species' lower motivation to utilize the outdoor spaces. Findings highlight species-specific reactions to access to choice that may offer insight for enclosure design, management, and nonhuman animal welfare.

  7. Culture extends the scope of evolutionary biology in the great apes

    PubMed Central

    2017-01-01

    Discoveries about the cultures and cultural capacities of the great apes have played a leading role in the recognition emerging in recent decades that cultural inheritance can be a significant factor in the lives not only of humans but also of nonhuman animals. This prominence derives in part from these primates being those with whom we share the most recent common ancestry, thus offering clues to the origins of our own thoroughgoing reliance on cumulative cultural achievements. In addition, the intense research focus on these species has spawned an unprecedented diversity of complementary methodological approaches, the results of which suggest that cultural phenomena pervade the lives of these apes, with potentially major implications for their broader evolutionary biology. Here I review what this extremely broad array of observational and experimental methodologies has taught us about the cultural lives of chimpanzees, gorillas, and orangutans and consider the ways in which this knowledge extends our wider understanding of primate biology and the processes of adaptation and evolution that shape it. I address these issues first by evaluating the extent to which the results of cultural inheritance echo a suite of core principles that underlie organic Darwinian evolution but also extend them in new ways and then by assessing the principal causal interactions between the primary, genetically based organic processes of evolution and the secondary system of cultural inheritance that is based on social learning from others. PMID:28739927

  8. Retrospective serology study of respiratory virus infections in captive great apes.

    PubMed

    Buitendijk, Hester; Fagrouch, Zahra; Niphuis, Henk; Bogers, Willy M; Warren, Kristin S; Verschoor, Ernst J

    2014-03-24

    Great apes are extremely sensitive to infections with human respiratory viruses. In this study, we retrospectively analyzed sera from captive chimpanzees, gorillas and orang-utans. More than 1000 sera (403 chimpanzee, 77 gorilla, and 535 orang-utan sera) were analyzed for antibodies to the human respiratory viruses RSV (respiratory syncytial virus, hMPV (human metapneumovirus), H1N1 and H3N2 influenza A viruses, and influenza B virus. In all ape species high seroprevalences were found for RSV, hMPV, and influenza B virus. A high percentage of captive chimpanzees also showed evidence of influenza A H1N1 infections, and had low levels of H3N2 antibodies, while in sera from gorillas and orangutans antibody levels to influenza A and B viruses were much lower or practically absent. Transmission of respiratory viruses was examined in longitudinal sera of young chimpanzees, and in chimpanzee sera taken during health checks. In young animals isolated cases of influenza infections were monitored, but evidence was found for single introductions followed by a rapid dissemination of RSV and hMPV within the group. Implementation of strict guidelines for handling and housing of nonhuman primates was shown to be an efficient method to reduce the introduction of respiratory infections in colonies of captive animals. RSV seroprevalence rates of chimpanzees remained high, probably due to circulating virus in the chimpanzee colony.

  9. Femoral morphology and femoropelvic musculoskeletal anatomy of humans and great apes: a comparative virtopsy study.

    PubMed

    Morimoto, Naoki; Ponce de León, Marcia S; Nishimura, Takeshi; Zollikofer, Christoph P E

    2011-09-01

    The proximal femoral morphology of fossil hominins is routinely interpreted in terms of muscular topography and associated locomotor modes. However, the detailed correspondence between hard and soft tissue structures in the proximal femoral region of extant great apes is relatively unknown, because dissection protocols typically do not comprise in-depth osteological descriptions. Here, we use computed tomography and virtopsy (virtual dissection) for non-invasive examination of the femoropelvic musculoskeletal anatomy in Pan troglodytes, P. paniscus, Gorilla gorilla, Pongo pygmaeus, and Homo sapiens. Specifically, we analyze the topographic relationship between muscle attachment sites and surface structures of the proximal femoral shaft such as the lateral spiral pilaster. Our results show that the origin of the vastus lateralis muscle is anterior to the insertion of gluteus maximus in all examined great ape specimens and humans. In gorillas and orangutans, the insertion of gluteus maximus is on the inferior (anterolateral) side of the lateral spiral pilaster. In chimpanzees, however, the maximus insertion is on its superior (posteromedial) side, similar to the situation in modern humans. These findings support the hypothesis that chimpanzees and humans exhibit a shared-derived musculoskeletal topography of the proximal femoral region, irrespective of their different locomotor modes, whereas gorillas and orangutans represent the primitive condition. Caution is thus warranted when inferring locomotor behavior from the surface topography of the proximal femur of fossil hominins, as the morphology of this region may contain a strong phyletic signal that tends to blur locomotor adaptation.

  10. Predicting the vulnerability of great apes to disease: the role of superspreaders and their potential vaccination.

    PubMed

    Carne, Charlotte; Semple, Stuart; Morrogh-Bernard, Helen; Zuberbühler, Klaus; Lehmann, Julia

    2013-01-01

    Disease is a major concern for the conservation of great apes, and one that is likely to become increasingly relevant as deforestation and the rise of ecotourism bring humans and apes into ever closer proximity. Consequently, it is imperative that preventative measures are explored to ensure that future epidemics do not wipe out the remaining populations of these animals. In this paper, social network analysis was used to investigate vulnerability to disease in a population of wild orang-utans and a community of wild chimpanzees. Potential 'superspreaders' of disease--individuals with disproportionately central positions in the community or population--were identified, and the efficacy of vaccinating these individuals assessed using simulations. Three resident female orang-utans were identified as potential superspreaders, and females and unflanged males were predicted to be more influential in disease spread than flanged males. By contrast, no superspreaders were identified in the chimpanzee network, although males were significantly more central than females. In both species, simulating the vaccination of the most central individuals in the network caused a greater reduction in potential disease pathways than removing random individuals, but this effect was considerably more pronounced for orang-utans. This suggests that targeted vaccinations would have a greater impact on reducing disease spread among orang-utans than chimpanzees. Overall, these results have important implications for orang-utan and chimpanzee conservation and highlight the role that certain individuals may play in the spread of disease and its prevention by vaccination.

  11. Positive selection of a gene family during the emergence of humans and African apes.

    PubMed

    Johnson, M E; Viggiano, L; Bailey, J A; Abdul-Rauf, M; Goodwin, G; Rocchi, M; Eichler, E E

    2001-10-04

    Gene duplication followed by adaptive evolution is one of the primary forces for the emergence of new gene function. Here we describe the recent proliferation, transposition and selection of a 20-kilobase (kb) duplicated segment throughout 15 Mb of the short arm of human chromosome 16. The dispersal of this segment was accompanied by considerable variation in chromosomal-map location and copy number among hominoid species. In humans, we identified a gene family (morpheus) within the duplicated segment. Comparison of putative protein-encoding exons revealed the most extreme case of positive selection among hominoids. The major episode of enhanced amino-acid replacement occurred after the separation of human and great-ape lineages from the orangutan. Positive selection continued to alter amino-acid composition after the divergence of human and chimpanzee lineages. The rapidity and bias for amino-acid-altering nucleotide changes suggest adaptive evolution of the morpheus gene family during the emergence of humans and African apes. Moreover, some genes emerge and evolve very rapidly, generating copies that bear little similarity to their ancestral precursors. Consequently, a small fraction of human genes may not possess discernible orthologues within the genomes of model organisms.

  12. Evidence for a midlife crisis in great apes consistent with the U-shape in human well-being.

    PubMed

    Weiss, Alexander; King, James E; Inoue-Murayama, Miho; Matsuzawa, Tetsuro; Oswald, Andrew J

    2012-12-04

    Recently, economists and behavioral scientists have studied the pattern of human well-being over the lifespan. In dozens of countries, and for a large range of well-being measures, including happiness and mental health, well-being is high in youth, falls to a nadir in midlife, and rises again in old age. The reasons for this U-shape are still unclear. Present theories emphasize sociological and economic forces. In this study we show that a similar U-shape exists in 508 great apes (two samples of chimpanzees and one sample of orangutans) whose well-being was assessed by raters familiar with the individual apes. This U-shaped pattern or "midlife crisis" emerges with or without use of parametric methods. Our results imply that human well-being's curved shape is not uniquely human and that, although it may be partly explained by aspects of human life and society, its origins may lie partly in the biology we share with great apes. These findings have implications across scientific and social-scientific disciplines, and may help to identify ways of enhancing human and ape well-being.

  13. Locational Diversity of Alpha Satellite DNA and Intergeneric Hybridization Aspects in the Nomascus and Hylobates Genera of Small Apes

    PubMed Central

    Baicharoen, Sudarath; Miyabe-Nishiwaki, Takako; Arsaithamkul, Visit; Hirai, Yuriko; Duangsa-ard, Kwanruen; Siriaroonrat, Boripat; Domae, Hiroshi; Srikulnath, Kornsorn; Koga, Akihiko; Hirai, Hirohisa

    2014-01-01

    Recently, we discovered that alpha satellite DNA has unique and genus-specific localizations on the chromosomes of small apes. This study describes the details of alpha satellite localization in the genera Nomascus and Hylobates and explores their usefulness in distinguishing parental genome sets in hybrids between these genera. Fluorescence in situ hybridization was used to establish diagnostic criteria of alpha satellite DNA markers in discriminating small ape genomes. In particular we established the genus specificity of alpha satellite distribution in three species of light-cheeked gibbons (Nomascus leucogenys, N. siki, and N. gabriellae) in comparison to that of Hylobates lar. Then we determined the localization of alpha satellite DNA in a hybrid individual which resulted from a cross between these two genera. In Nomascus the alpha satellite DNA blocks were located at the centromere, telomere, and four interstitial regions. In Hylobates detectable amounts of alpha satellite DNA were seen only at centromeric regions. The differences in alpha satellite DNA locations between Nomascus and Hylobates allowed us to easily distinguish the parental chromosomal sets in the genome of intergeneric hybrid individuals found in Thai and Japanese zoos. Our study illustrates how molecular cytogenetic markers can serve as diagnostic tools to identify the origin of individuals. These molecular tools can aid zoos, captive breeding programs and conservation efforts in managing small apes species. Discovering more information on alpha satellite distribution is also an opportunity to examine phylogenetic and evolutionary questions that are still controversial in small apes. PMID:25290445

  14. Locational diversity of alpha satellite DNA and intergeneric hybridization aspects in the Nomascus and Hylobates genera of small apes.

    PubMed

    Baicharoen, Sudarath; Miyabe-Nishiwaki, Takako; Arsaithamkul, Visit; Hirai, Yuriko; Duangsa-ard, Kwanruen; Siriaroonrat, Boripat; Domae, Hiroshi; Srikulnath, Kornsorn; Koga, Akihiko; Hirai, Hirohisa

    2014-01-01

    Recently, we discovered that alpha satellite DNA has unique and genus-specific localizations on the chromosomes of small apes. This study describes the details of alpha satellite localization in the genera Nomascus and Hylobates and explores their usefulness in distinguishing parental genome sets in hybrids between these genera. Fluorescence in situ hybridization was used to establish diagnostic criteria of alpha satellite DNA markers in discriminating small ape genomes. In particular we established the genus specificity of alpha satellite distribution in three species of light-cheeked gibbons (Nomascus leucogenys, N. siki, and N. gabriellae) in comparison to that of Hylobates lar. Then we determined the localization of alpha satellite DNA in a hybrid individual which resulted from a cross between these two genera. In Nomascus the alpha satellite DNA blocks were located at the centromere, telomere, and four interstitial regions. In Hylobates detectable amounts of alpha satellite DNA were seen only at centromeric regions. The differences in alpha satellite DNA locations between Nomascus and Hylobates allowed us to easily distinguish the parental chromosomal sets in the genome of intergeneric hybrid individuals found in Thai and Japanese zoos. Our study illustrates how molecular cytogenetic markers can serve as diagnostic tools to identify the origin of individuals. These molecular tools can aid zoos, captive breeding programs and conservation efforts in managing small apes species. Discovering more information on alpha satellite distribution is also an opportunity to examine phylogenetic and evolutionary questions that are still controversial in small apes.

  15. Evidence for a midlife crisis in great apes consistent with the U-shape in human well-being

    PubMed Central

    Weiss, Alexander; King, James E.; Inoue-Murayama, Miho; Matsuzawa, Tetsuro; Oswald, Andrew J.

    2012-01-01

    Recently, economists and behavioral scientists have studied the pattern of human well-being over the lifespan. In dozens of countries, and for a large range of well-being measures, including happiness and mental health, well-being is high in youth, falls to a nadir in midlife, and rises again in old age. The reasons for this U-shape are still unclear. Present theories emphasize sociological and economic forces. In this study we show that a similar U-shape exists in 508 great apes (two samples of chimpanzees and one sample of orangutans) whose well-being was assessed by raters familiar with the individual apes. This U-shaped pattern or “midlife crisis” emerges with or without use of parametric methods. Our results imply that human well-being’s curved shape is not uniquely human and that, although it may be partly explained by aspects of human life and society, its origins may lie partly in the biology we share with great apes. These findings have implications across scientific and social-scientific disciplines, and may help to identify ways of enhancing human and ape well-being. PMID:23169637

  16. Neuronal populations in the basolateral nuclei of the amygdala are differentially increased in humans compared with apes: a stereological study.

    PubMed

    Barger, Nicole; Stefanacci, Lisa; Schumann, Cynthia M; Sherwood, Chet C; Annese, Jacopo; Allman, John M; Buckwalter, Joseph A; Hof, Patrick R; Semendeferi, Katerina

    2012-09-01

    In human and nonhuman primates, the amygdala is known to play critical roles in emotional and social behavior. Anatomically, individual amygdaloid nuclei are connected with many neural systems that are either differentially expanded or conserved over the course of primate evolution. To address amygdala evolution in humans and our closest living relatives, the apes, we used design-based stereological methods to obtain neuron counts for the amygdala and each of four major amygdaloid nuclei (the lateral, basal, accessory basal, and central nuclei) in humans, all great ape species, lesser apes, and one monkey species. Our goal was to determine whether there were significant differences in the number or percent of neurons distributed to individual nuclei among species. Additionally, regression analyses were performed on independent contrast data to determine whether any individual species deviated from allometric trends. There were two major findings. In humans, the lateral nucleus contained the highest number of neurons in the amygdala, whereas in apes the basal nucleus contained the highest number of neurons. Additionally, the human lateral nucleus contained 59% more neurons than predicted by allometric regressions on nonhuman primate data. Based on the largest sample ever analyzed in a comparative study of the hominoid amygdala, our findings suggest that an emphasis on the lateral nucleus is the main characteristic of amygdala specialization over the course of human evolution. Copyright © 2012 Wiley Periodicals, Inc.

  17. What Does an Intermediate Success Rate Mean? An Analysis of a Piagetian Liquid Conservation Task in the Great Apes

    ERIC Educational Resources Information Center

    Suda, Chikako; Call, Josep

    2006-01-01

    The study investigates what an intermediate success rate means in bonobos, chimpanzees, and orangutans. Apes participated in liquid conservation experiments where they had to track the larger of two different quantities of juice after various kinds of transformations [Suda, C., & Call, J. (2004). Piagetian liquid conservation in the great apes…

  18. The Role of Socio-Communicative Rearing Environments in the Development of Social and Physical Cognition in Apes

    ERIC Educational Resources Information Center

    Russell, Jamie L.; Lyn, Heidi; Schaeffer, Jennifer A.; Hopkins, William D.

    2011-01-01

    The cultural intelligence hypothesis (CIH) claims that humans' advanced cognition is a direct result of human culture and that children are uniquely specialized to absorb and utilize this cultural experience (Tomasello, 2000). Comparative data demonstrating that 2.5-year-old human children outperform apes on measures of social cognition but not on…

  19. Conservation Education and Environmental Communication in Great Ape Re-Introduction Projects: Two Cases from the Republic of Congo

    ERIC Educational Resources Information Center

    Cartwright, Barbara J.; Wall, John E.; Kaya, J. A. Placide

    2012-01-01

    Among species recovery tools available, re-introduction of animals to the wild is one of the more complex. Since the mid-1990s two successful great ape re-introductions have taken place in the Republic of Congo, leading some conservationists to revisit re-introduction as a strategy. This research explored the role of conservation education and…

  20. What Does an Intermediate Success Rate Mean? An Analysis of a Piagetian Liquid Conservation Task in the Great Apes

    ERIC Educational Resources Information Center

    Suda, Chikako; Call, Josep

    2006-01-01

    The study investigates what an intermediate success rate means in bonobos, chimpanzees, and orangutans. Apes participated in liquid conservation experiments where they had to track the larger of two different quantities of juice after various kinds of transformations [Suda, C., & Call, J. (2004). Piagetian liquid conservation in the great apes…

  1. Human rather than ape-like orbital morphology allows much greater lateral visual field expansion with eye abduction

    PubMed Central

    Denion, Eric; Hitier, Martin; Levieil, Eric; Mouriaux, Frédéric

    2015-01-01

    While convergent, the human orbit differs from that of non-human apes in that its lateral orbital margin is significantly more rearward. This rearward position does not obstruct the additional visual field gained through eye motion. This additional visual field is therefore considered to be wider in humans than in non-human apes. A mathematical model was designed to quantify this difference. The mathematical model is based on published computed tomography data in the human neuro-ocular plane (NOP) and on additional anatomical data from 100 human skulls and 120 non-human ape skulls (30 gibbons; 30 chimpanzees / bonobos; 30 orangutans; 30 gorillas). It is used to calculate temporal visual field eccentricity values in the NOP first in the primary position of gaze then for any eyeball rotation value in abduction up to 45° and any lateral orbital margin position between 85° and 115° relative to the sagittal plane. By varying the lateral orbital margin position, the human orbit can be made “non-human ape-like”. In the Pan-like orbit, the orbital margin position (98.7°) was closest to the human orbit (107.1°). This modest 8.4° difference resulted in a large 21.1° difference in maximum lateral visual field eccentricity with eyeball abduction (Pan-like: 115°; human: 136.1°). PMID:26190625

  2. Conservation Education and Environmental Communication in Great Ape Re-Introduction Projects: Two Cases from the Republic of Congo

    ERIC Educational Resources Information Center

    Cartwright, Barbara J.; Wall, John E.; Kaya, J. A. Placide

    2012-01-01

    Among species recovery tools available, re-introduction of animals to the wild is one of the more complex. Since the mid-1990s two successful great ape re-introductions have taken place in the Republic of Congo, leading some conservationists to revisit re-introduction as a strategy. This research explored the role of conservation education and…

  3. The Role of Socio-Communicative Rearing Environments in the Development of Social and Physical Cognition in Apes

    ERIC Educational Resources Information Center

    Russell, Jamie L.; Lyn, Heidi; Schaeffer, Jennifer A.; Hopkins, William D.

    2011-01-01

    The cultural intelligence hypothesis (CIH) claims that humans' advanced cognition is a direct result of human culture and that children are uniquely specialized to absorb and utilize this cultural experience (Tomasello, 2000). Comparative data demonstrating that 2.5-year-old human children outperform apes on measures of social cognition but not on…

  4. Culture in great apes: using intricate complexity in feeding skills to trace the evolutionary origin of human technical prowess.

    PubMed

    Byrne, Richard W

    2007-04-29

    Geographical cataloguing of traits, as used in human ethnography, has led to the description of 'culture' in some non-human great apes. Culture, in these terms, is detected as a pattern of local ignorance resulting from environmental constraints on knowledge transmission. However, in many cases, the geographical variations may alternatively be explained by ecology. Social transmission of information can reliably be identified in many other animal species, by experiment or distinctive patterns in distribution; but the excitement of detecting culture in great apes derives from the possibility of understanding the evolution of cumulative technological culture in humans. Given this interest, I argue that great ape research should concentrate on technically complex behaviour patterns that are ubiquitous within a local population; in these cases, a wholly non-social ontogeny is highly unlikely. From this perspective, cultural transmission has an important role in the elaborate feeding skills of all species of great ape, in conveying the 'gist' or organization of skills. In contrast, social learning is unlikely to be responsible for local stylistic differences, which are apt to reflect sensitive adaptations to ecology.

  5. Evaluating the effect of a year-long film focused environmental education program on Ugandan student knowledge of and attitudes toward great apes.

    PubMed

    Leeds, Austin; Lukas, Kristen E; Kendall, Corinne J; Slavin, Michelle A; Ross, Elizabeth A; Robbins, Martha M; van Weeghel, Dagmar; Bergl, Richard A

    2017-08-01

    Films, as part of a larger environmental education program, have the potential to influence the knowledge and attitudes of viewers. However, to date, no evaluations have been published reporting the effectiveness of films, when used within primate range countries as part of a conservation themed program. The Great Ape Education Project was a year-long environmental education program implemented in Uganda for primary school students living adjacent to Kibale National Park (KNP) and Bwindi Impenetrable National Park (BINP). Students viewed a trilogy of conservation films about great apes, produced specifically for this audience, and participated in complementary extra-curricular activities. The knowledge and attitudes of students participating in the program from KNP, but not BINP were assessed using questionnaires prior to (N = 1271) and following (N = 872) the completion of the program. Following the program, students demonstrated a significant increase in their knowledge of threats to great apes and an increase in their knowledge of ways that villagers and students can help conserve great apes. Additionally, student attitudes toward great apes improved following the program. For example, students showed an increase in agreement with liking great apes and viewing them as important to the environment. These data provide evidence that conservation films made specifically to address regional threats and using local actors and settings can positively influence knowledge of and attitudes toward great apes among students living in a primate range country. © 2017 Wiley Periodicals, Inc.

  6. Cross-institutional knowledge-based planning (KBP) implementation and its performance comparison to Auto-Planning Engine (APE).

    PubMed

    Wu, Binbin; Kusters, Martijn; Kunze-Busch, Martina; Dijkema, Tim; McNutt, Todd; Sanguineti, Giuseppe; Bzdusek, Karl; Dritschilo, Anatoly; Pang, Dalong

    2017-04-01

    To investigate (1) whether a plan library established at one institution can be applied for another institution's knowledge-based planning (KBP); (2) the performance of cross-institutional KBP compared to Auto-Planning Engine (APE). Radboud University Medical Center (RUMC) provided 35 oropharyngeal cancer patients (68Gy to PTV(68) and 50.3Gy to PTV(50.3)) with clinically-delivered and comparative APE plans. The Johns Hopkins University (JHU) contributed a three-dose-level plan library consisting of 179 clinically-delivered plans. MedStar Georgetown University Hospital (MGUH) contributed a KBP approach employing overlap-volume histogram (OVH-KBP), where the JHU library was used for guiding RUMC patients' KBP. Since clinical protocols adopted at RUMC and JHU are different and both approaches require protocol-specific planning parameters as initial input, 10 randomly selected patients from RUMC were set aside for deriving them. The finalized parameters were applied to the remaining 25 patients for OVH-KBP and APE plan generation. A Wilcoxon rank-sum test was used for statistical comparison. PTV(68) and PTV(50.3)'s V95 in OVH-KBP and APE were similar (p>0.36). Cord's D0.1 cc in OVH-KBP was reduced by 5.1Gy (p=0.0001); doses to other organs were similar (p>0.2). APE and OVH-KBP's plan quality is comparable. Institutional-protocol differences can be addressed to allow cross-institutional library sharing. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Bonobo habituation in a forest-savanna mosaic habitat: influence of ape species, habitat type, and sociocultural context.

    PubMed

    Narat, Victor; Pennec, Flora; Simmen, Bruno; Ngawolo, Jean Christophe Bokika; Krief, Sabrina

    2015-10-01

    Habituation is the term used to describe acceptance by wild animals of a human observer as a neutral element in their environment. Among primates, the process takes from a few days for Galago spp. to several years for African apes. There are also intraspecies differences reflecting differences in habitat, home range, and ape-human relationship history. Here, we present the first study of the process of bonobo habituation in a fragmented habitat, a forest-savanna mosaic in the community-based conservation area led by the Congolese nongovernmental organization Mbou-Mon-Tour, Democratic Republic of the Congo. In this area, local people use the forest almost every day for traditional activities but avoid bonobos because of a traditional taboo. Because very few flight reactions were observed during habituation, we focused on quantitative parameters to assess the development of ape tolerance and of the tracking efficiency of observer teams. During the 18-month study period (May 2012-October 2013), 4043 h (319 days) were spent in the forest and bonobos were observed for a total of 405 h (196 contacts on 134 days). The average contact duration was stable over time (124 min), but the minimal distance during a contact decreased with habituation effort. Moreover, bonobo location and tracking efficiency, daily ratio of contact time to habituation effort, and the number of observations at ground level were positively correlated with habituation effort. Our observations suggest that bonobos become habituated relatively rapidly. These results are discussed in relation to the habitat type, ape species, and the local sociocultural context of villagers. The habituation process involves changes in ape behavior toward observers and also more complex interactions concerning the ecosystem, including the building of an efficient local team. Before starting a habituation process, knowledge of the human sociocultural context is essential to assess the balance between risks and benefits.

  8. Impact of reduced levels of APE1 transcripts on the survival of patients with urothelial carcinoma of the bladder

    PubMed Central

    CHANTRE-JUSTINO, MARIANA; ALVES, GILDA; BRITTO, CONSTANÇA; CARDOSO, ANGÉLICA; SCHERRER, LUCIANO; MOREIRA, ALINE DOS SANTOS; QUIRINO, RAUL; ORNELLAS, ANTONIO; LEITÃO, ALVARO; LAGE, CLAUDIA

    2015-01-01

    Molecular evidence indicates that alterations in genes involved in the maintenance of genome stability may be related to susceptibility to bladder carcinoma. Our goal was to evaluate the prognostic role of base excision repair (BER) genes in a cohort of patients diagnosed with primary urothelial carcinoma of the bladder (UCB). The levels of all APE1, XRCC1 and POLB transcripts were detected by quantitative real-time PCR (qPCR) technique in tumor samples from 52 patients undergoing transurethral resection (TUR) for primary UCB at the Department of Urology, Brazilian National Cancer Institute, Rio de Janeiro. Increased levels of APE1, XRCC1 and POLB transcripts were significantly associated with high-grade tumors when compared to these levels in low-grade tumors (p<0.01) and could be attributed to different mechanisms of transcriptional regulation as a response to tumorigenesis and oxidative stress. By analyzing the collected data in the present study, regardless of pathological grade or stage, univariate analysis revealed that the reduced levels of APE1 transcripts were significantly associated with cancer-specific mortality (p=0.032). Furthermore, the variant genotype (TG/GG) of the APE1 T1349G polymorphism was observed in 75% of a subset of patients who concomitantly experienced reduced levels of the APE1 transcript and death and/or recurrence events. Taken together, our data reinforce the idea that human DNA repair mechanisms must be finely regulated in order to avoid instability leading to tumorigenesis and poor clinical outcomes in UCB patients. PMID:26238022

  9. Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria.

    PubMed

    Sundararaman, Sesh A; Liu, Weimin; Keele, Brandon F; Learn, Gerald H; Bittinger, Kyle; Mouacha, Fatima; Ahuka-Mundeke, Steve; Manske, Magnus; Sherrill-Mix, Scott; Li, Yingying; Malenke, Jordan A; Delaporte, Eric; Laurent, Christian; Mpoudi Ngole, Eitel; Kwiatkowski, Dominic P; Shaw, George M; Rayner, Julian C; Peeters, Martine; Sharp, Paul M; Bushman, Frederic D; Hahn, Beatrice H

    2013-04-23

    Wild-living chimpanzees and gorillas harbor a multitude of Plasmodium species, including six of the subgenus Laverania, one of which served as the progenitor of Plasmodium falciparum. Despite the magnitude of this reservoir, it is unknown whether apes represent a source of human infections. Here, we used Plasmodium species-specific PCR, single-genome amplification, and 454 sequencing to screen humans from remote areas of southern Cameroon for ape Laverania infections. Among 1,402 blood samples, we found 1,000 to be Plasmodium mitochondrial DNA (mtDNA) positive, all of which contained human parasites as determined by sequencing and/or restriction enzyme digestion. To exclude low-abundance infections, we subjected 514 of these samples to 454 sequencing, targeting a region of the mtDNA genome that distinguishes ape from human Laverania species. Using algorithms specifically developed to differentiate rare Plasmodium variants from 454-sequencing error, we identified single and mixed-species infections with P. falciparum, Plasmodium malariae, and/or Plasmodium ovale. However, none of the human samples contained ape Laverania parasites, including the gorilla precursor of P. falciparum. To characterize further the diversity of P. falciparum in Cameroon, we used single-genome amplification to amplify 3.4-kb mtDNA fragments from 229 infected humans. Phylogenetic analysis identified 62 new variants, all of which clustered with extant P. falciparum, providing further evidence that P. falciparum emerged following a single gorilla-to-human transmission. Thus, unlike Plasmodium knowlesi-infected macaques in southeast Asia, African apes harboring Laverania parasites do not seem to serve as a recurrent source of human malaria, a finding of import to ongoing control and eradication measures.

  10. Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria

    PubMed Central

    Sundararaman, Sesh A.; Liu, Weimin; Keele, Brandon F.; Learn, Gerald H.; Bittinger, Kyle; Mouacha, Fatima; Ahuka-Mundeke, Steve; Manske, Magnus; Sherrill-Mix, Scott; Li, Yingying; Malenke, Jordan A.; Delaporte, Eric; Laurent, Christian; Mpoudi Ngole, Eitel; Kwiatkowski, Dominic P.; Shaw, George M.; Rayner, Julian C.; Peeters, Martine; Sharp, Paul M.; Bushman, Frederic D.; Hahn, Beatrice H.

    2013-01-01

    Wild-living chimpanzees and gorillas harbor a multitude of Plasmodium species, including six of the subgenus Laverania, one of which served as the progenitor of Plasmodium falciparum. Despite the magnitude of this reservoir, it is unknown whether apes represent a source of human infections. Here, we used Plasmodium species-specific PCR, single-genome amplification, and 454 sequencing to screen humans from remote areas of southern Cameroon for ape Laverania infections. Among 1,402 blood samples, we found 1,000 to be Plasmodium mitochondrial DNA (mtDNA) positive, all of which contained human parasites as determined by sequencing and/or restriction enzyme digestion. To exclude low-abundance infections, we subjected 514 of these samples to 454 sequencing, targeting a region of the mtDNA genome that distinguishes ape from human Laverania species. Using algorithms specifically developed to differentiate rare Plasmodium variants from 454-sequencing error, we identified single and mixed-species infections with P. falciparum, Plasmodium malariae, and/or Plasmodium ovale. However, none of the human samples contained ape Laverania parasites, including the gorilla precursor of P. falciparum. To characterize further the diversity of P. falciparum in Cameroon, we used single-genome amplification to amplify 3.4-kb mtDNA fragments from 229 infected humans. Phylogenetic analysis identified 62 new variants, all of which clustered with extant P. falciparum, providing further evidence that P. falciparum emerged following a single gorilla-to-human transmission. Thus, unlike Plasmodium knowlesi-infected macaques in southeast Asia, African apes harboring Laverania parasites do not seem to serve as a recurrent source of human malaria, a finding of import to ongoing control and eradication measures. PMID:23569255

  11. Screening wild and semi-free ranging great apes for putative sexually transmitted diseases: Evidence of Trichomonadidae infections.

    PubMed

    Rushmore, Julie; Allison, Andrew B; Edwards, Erin E; Bagal, Ujwal; Altizer, Sonia; Cranfield, Mike R; Glenn, Travis C; Liu, Hsi; Mudakikwa, Antoine; Mugisha, Lawrence; Muller, Martin N; Stumpf, Rebecca M; Thompson, Melissa Emery; Wrangham, Richard; Yabsley, Michael J

    2015-10-01

    Sexually transmitted diseases (STDs) can persist endemically, are known to cause sterility and infant mortality in humans, and could have similar impacts in wildlife populations. African apes (i.e., chimpanzees, bonobos, and to a lesser extent gorillas) show multi-male mating behavior that could offer opportunities for STD transmission, yet little is known about the prevalence and impact of STDs in this endangered primate group. We used serology and PCR-based detection methods to screen biological samples from wild and orphaned eastern chimpanzees and gorillas (N = 172 individuals, including adults, and juveniles) for four classes of pathogens that either commonly cause human STDs or were previously detected in captive apes: trichomonads, Chlamydia spp., Treponema pallidum (syphilis and yaws), and papillomaviruses. Based on results from prior modeling and comparative research, we expected STD prevalence to be highest in females versus males and in sexually mature versus immature individuals. All samples were negative for Chlamydia, Treponema pallidum, and papillomaviruses; however, a high percentage of wild chimpanzee urine and fecal samples showed evidence of trichomonads (protozoa). Analysis revealed that females were more likely than males to have positive urine-but not fecal-samples; however, there was no evidence of age (sexual maturity) differences in infection status. Sequence analysis of chimpanzee trichomonad samples revealed a close relationship to previously described trichomonads within the genus Tetratrichomonas. Phylogenetic comparisons to archived sequences from multiple vertebrate hosts suggests that many of the chimpanzee parasites from our study are likely transmitted via fecal-oral contact, but the transmission of some Tetratrichomonas sequence-types remains unknown and could include sexual contact. Our work emphasizes that only a fraction of infectious agents affecting wild apes are presently known to science, and that further work on great

  12. Mona Lisa smile: the morphological enigma of human and great ape evolution.

    PubMed

    Grehan, John R

    2006-07-01

    The science of human evolution is confronted with the popular chimpanzee theory and the earlier but largely ignored orangutan theory. The quality and scope of published documentation and verification of morphological features suggests there is very little in morphology to support a unique common ancestor for humans and chimpanzees. A close relationship between humans and African apes is currently supported by only eight unproblematic characters. The orangutan relationship is supported by about 28 well-supported characters, and it is also corroborated by the presence of orangutan-related features in early hominids. The uniquely shared morphology of humans and orangutans raises doubts about the almost universal belief that DNA sequence similarities necessarily demonstrate a closer evolutionary relationship between humans and chimpanzees. A new evolutionary reconstruction is proposed for the soft tissue anatomy, physiology, and behavioral biology of the first hominids that includes concealed ovulation, male beard and mustache, prolonged mating, extended pair-bonding, "house" construction, mechanical "genius," and artistic expression.

  13. The spread of a novel behavior in wild chimpanzees: New insights into the ape cultural mind

    PubMed Central

    Gruber, Thibaud; Poisot, Timothée; Zuberbühler, Klaus; Hoppitt, William; Hobaiter, Catherine

    2015-01-01

    For years, the animal culture debate has been dominated by the puzzling absence of direct evidence for social transmission of behavioral innovations in the flagship species of animal culture, the common chimpanzee. Although social learning of novel behaviors has been documented in captivity, critics argue that these findings lack ecological validity and therefore may not be relevant for understanding the evolution of culture. For the wild, it is possible that group-specific behavioral differences emerge because group members respond individually to unspecified environmental differences, rather than learning from each other. In a recent paper, we used social network analyses in wild chimpanzees (Pan troglodytes schweinfurthii) to provide direct evidence for social transmission of a behavioral innovation, moss-sponging, to extract water from a tree hole. Here, we discuss the implications of our findings and how our new methodological approach could help future studies of social learning and culture in wild apes. PMID:26479151

  14. RNAi Knockdown of Ape1 Gene in the Differentiation of Mouse Embryonic Stem Cells.

    PubMed

    Zou, Gang-Ming; Yu, Jieqing; LeBron, Cynthia; Fu, Yumei

    2017-01-01

    Murine embryonic stem cells (ES) are pluripotent cells and have the potential to become a wide variety of specialized cell types. Mouse ES cell differentiation can be regarded as a valuable biological tool that has led to major advances in our understanding of cell and developmental biology. In vitro differentiation of mouse ES cells can be directed to a specific lineage formation, such as hematopoietic lineage, by appropriate cytokine and/or growth factor stimulation. To study specific gene function in early developmental events, gene knockout approaches have been traditionally used, however, this is a time-consuming and expensive approach. Recently, we have shown that siRNA is an effective strategy to knock down target gene expression, such as Ape1, during ES cell differentiation, and consequently, one can alter cell fates in ES-derived differentiated cells. This approach will be applicable to test the function of a wide variety of gene products using the ES cell differentiation system.

  15. RNAi knockdown of redox signaling protein Ape1 in the differentiation of mouse embryonic stem cells.

    PubMed

    Zou, Gang-Ming; Lebron, Cynthia; Fu, Yumei

    2010-01-01

    Murine embryonic stem cells (ES) are pluripotent cells and have the potential to become a wide variety of specialized cell types. Mouse ES cell differentiation can be regarded as a valuable biological tool that has led to major advances in our understanding of cell and developmental biology. In vitro differentiation of mouse ES cells can be directed to a specific lineage formation, such as hematopoietic lineage, by appropriate cytokine and/or growth factor stimulation. To study specific gene function in early developmental events, gene knockout approaches have been traditionally used; however, this is a time-consuming and expensive approach. Recently, we have shown that siRNA is an effective strategy to knockdown target gene expression, such as Ape1, during ES cell differentiation, and consequently, one can alter cell fates in ES-derived differentiated cells. This approach will be applicable to test the function of a wide variety of gene products using the ES cell differentiation system.

  16. The spread of a novel behavior in wild chimpanzees: New insights into the ape cultural mind.

    PubMed

    Gruber, Thibaud; Poisot, Timothée; Zuberbühler, Klaus; Hoppitt, William; Hobaiter, Catherine

    2015-01-01

    For years, the animal culture debate has been dominated by the puzzling absence of direct evidence for social transmission of behavioral innovations in the flagship species of animal culture, the common chimpanzee. Although social learning of novel behaviors has been documented in captivity, critics argue that these findings lack ecological validity and therefore may not be relevant for understanding the evolution of culture. For the wild, it is possible that group-specific behavioral differences emerge because group members respond individually to unspecified environmental differences, rather than learning from each other. In a recent paper, we used social network analyses in wild chimpanzees (Pan troglodytes schweinfurthii) to provide direct evidence for social transmission of a behavioral innovation, moss-sponging, to extract water from a tree hole. Here, we discuss the implications of our findings and how our new methodological approach could help future studies of social learning and culture in wild apes.

  17. A new look at the origins of gibbon ape leukemia virus.

    PubMed

    McKee, J; Clark, N; Shapter, F; Simmons, G

    2017-04-01

    Is the origin of gibbon ape leukemia virus (GALV) human after all? When GALV was discovered and found to cause neoplastic disease in gibbons, it stimulated a great deal of research including investigations into the origins of this virus. A number of publications have suggested that the GALV progenitor was a retrovirus present in one of several species of South East Asian rodents that had close contact with captive gibbons. However, there are no published retroviral sequences from any South East Asian species to support this view. Here we present an alternative hypothesis that the origin of GALV is a virus closely related to Melomys burtoni retrovirus, and that this virus infected human patients in Papua New Guinea from whom biological material was obtained or in some way contaminated these samples. This material we propose contained infectious MbRV-related virus that was then unwittingly introduced into gibbons which subsequently developed GALV infections.

  18. A nonverbal false belief task: the performance of children and great apes.

    PubMed

    Call, J; Tomasello, M

    1999-01-01

    A nonverbal task of false belief understanding was given to 4- and 5-year-old children (N = 28) and to two species of great ape: chimpanzees and orangutans (N = 7). The task was embedded in a series of finding games in which an adult (the hider) hid a reward in one of two identical containers, and another adult (the communicator) observed the hiding process and attempted to help the participant by placing a marker on the container that she believed to hold the reward. An initial series of control trials ensured that participants were able to use the marker to locate the reward, follow the reward in both visible and invisible displacements, and ignore the marker when they knew it to be incorrect. In the crucial false belief trials, the communicator watched the hiding process and then left the area, at which time the hider switched the locations of the containers. When the communicator returned, she marked the container at the location where she had seen the reward hidden, which was incorrect. The hider then gave the subject the opportunity to find the sticker. Successful performance required participants to reason as follows: the communicator placed the marker where she saw the reward hidden; the container that was at that location is now at the other location; so the reward is at the other location. Children were also given a verbal false belief task in the context of this same hiding game. The two main results of the study were: (1) children's performance on the verbal and nonverbal false belief tasks were highly correlated (and both fit very closely with age norms from previous studies), and (2) no ape succeeded in the nonverbal false belief task even though they succeeded in all of the control trials indicating mastery of the general task demands.

  19. Forearm articular proportions and the antebrachial index in Homo sapiens, Australopithecus afarensis and the great apes.

    PubMed

    Williams, Frank L'Engle; Cunningham, Deborah L; Amaral, Lia Q

    2015-12-01

    When hominin bipedality evolved, the forearms were free to adopt nonlocomotor tasks which may have resulted in changes to the articular surfaces of the ulna and the relative lengths of the forearm bones. Similarly, sex differences in forearm proportions may be more likely to emerge in bipeds than in the great apes given the locomotor constraints in Gorilla, Pan and Pongo. To test these assumptions, ulnar articular proportions and the antebrachial index (radius length/ulna length) in Homo sapiens (n=51), Gorilla gorilla (n=88), Pan troglodytes (n=49), Pongo pygmaeus (n=36) and Australopithecus afarensis A.L. 288-1 and A.L. 438-1 are compared. Intercept-adjusted ratios are used to control for size and minimize the effects of allometry. Canonical scores axes show that the proximally broad and elongated trochlear notch with respect to size in H. sapiens and A. afarensis is largely distinct from G. gorilla, P. troglodytes and P. pygmaeus. A cluster analysis of scaled ulnar articular dimensions groups H. sapiens males with A.L. 438-1 ulna length estimates, while one A.L. 288-1 ulna length estimate groups with Pan and another clusters most closely with H. sapiens, G. gorilla and A.L. 438-1. The relatively low antebrachial index characterizing H. sapiens and non-outlier estimates of A.L. 288-1 and A.L. 438-1 differs from those of the great apes. Unique sex differences in H. sapiens suggest a link between bipedality and forearm functional morphology. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Assessing Host-Virus Codivergence for Close Relatives of Merkel Cell Polyomavirus Infecting African Great Apes.

    PubMed

    Madinda, Nadège F; Ehlers, Bernhard; Wertheim, Joel O; Akoua-Koffi, Chantal; Bergl, Richard A; Boesch, Christophe; Akonkwa, Dieudonné Boji Mungu; Eckardt, Winnie; Fruth, Barbara; Gillespie, Thomas R; Gray, Maryke; Hohmann, Gottfried; Karhemere, Stomy; Kujirakwinja, Deo; Langergraber, Kevin; Muyembe, Jean-Jacques; Nishuli, Radar; Pauly, Maude; Petrzelkova, Klara J; Robbins, Martha M; Todd, Angelique; Schubert, Grit; Stoinski, Tara S; Wittig, Roman M; Zuberbühler, Klaus; Peeters, Martine; Leendertz, Fabian H; Calvignac-Spencer, Sébastien

    2016-10-01

    It has long been hypothesized that polyomaviruses (PyV; family Polyomaviridae) codiverged with their animal hosts. In contrast, recent analyses suggested that codivergence may only marginally influence the evolution of PyV. We reassess this question by focusing on a single lineage of PyV infecting hominine hosts, the Merkel cell polyomavirus (MCPyV) lineage. By characterizing the genetic diversity of these viruses in seven African great ape taxa, we show that they exhibit very strong host specificity. Reconciliation analyses identify more codivergence than noncodivergence events. In addition, we find that a number of host and PyV divergence events are synchronous. Collectively, our results support codivergence as the dominant process at play during the evolution of the MCPyV lineage. More generally, our results add to the growing body of evidence suggesting an ancient and stable association of PyV and their animal hosts. The processes involved in viral evolution and the interaction of viruses with their hosts are of great scientific interest and public health relevance. It has long been thought that the genetic diversity of double-stranded DNA viruses was generated over long periods of time, similar to typical host evolutionary timescales. This was also hypothesized for polyomaviruses (family Polyomaviridae), a group comprising several human pathogens, but this remains a point of controversy. Here, we investigate this question by focusing on a single lineage of polyomaviruses that infect both humans and their closest relatives, the African great apes. We show that these viruses exhibit considerable host specificity and that their evolution largely mirrors that of their hosts, suggesting that codivergence with their hosts played a major role in their diversification. Our results provide statistical evidence in favor of an association of polyomaviruses and their hosts over millions of years. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. Assessing Host-Virus Codivergence for Close Relatives of Merkel Cell Polyomavirus Infecting African Great Apes

    PubMed Central

    Madinda, Nadège F.; Ehlers, Bernhard; Wertheim, Joel O.; Akoua-Koffi, Chantal; Bergl, Richard A.; Boesch, Christophe; Akonkwa, Dieudonné Boji Mungu; Eckardt, Winnie; Fruth, Barbara; Gillespie, Thomas R.; Gray, Maryke; Hohmann, Gottfried; Karhemere, Stomy; Kujirakwinja, Deo; Langergraber, Kevin; Muyembe, Jean-Jacques; Nishuli, Radar; Pauly, Maude; Petrzelkova, Klara J.; Robbins, Martha M.; Todd, Angelique; Schubert, Grit; Stoinski, Tara S.; Wittig, Roman M.; Zuberbühler, Klaus; Peeters, Martine; Leendertz, Fabian H.

    2016-01-01

    ABSTRACT It has long been hypothesized that polyomaviruses (PyV; family Polyomaviridae) codiverged with their animal hosts. In contrast, recent analyses suggested that codivergence may only marginally influence the evolution of PyV. We reassess this question by focusing on a single lineage of PyV infecting hominine hosts, the Merkel cell polyomavirus (MCPyV) lineage. By characterizing the genetic diversity of these viruses in seven African great ape taxa, we show that they exhibit very strong host specificity. Reconciliation analyses identify more codivergence than noncodivergence events. In addition, we find that a number of host and PyV divergence events are synchronous. Collectively, our results support codivergence as the dominant process at play during the evolution of the MCPyV lineage. More generally, our results add to the growing body of evidence suggesting an ancient and stable association of PyV and their animal hosts. IMPORTANCE The processes involved in viral evolution and the interaction of viruses with their hosts are of great scientific interest and public health relevance. It has long been thought that the genetic diversity of double-stranded DNA viruses was generated over long periods of time, similar to typical host evolutionary timescales. This was also hypothesized for polyomaviruses (family Polyomaviridae), a group comprising several human pathogens, but this remains a point of controversy. Here, we investigate this question by focusing on a single lineage of polyomaviruses that infect both humans and their closest relatives, the African great apes. We show that these viruses exhibit considerable host specificity and that their evolution largely mirrors that of their hosts, suggesting that codivergence with their hosts played a major role in their diversification. Our results provide statistical evidence in favor of an association of polyomaviruses and their hosts over millions of years. PMID:27440885

  2. The short legs of great apes: evidence for aggressive behavior in australopiths.

    PubMed

    Carrier, David R

    2007-03-01

    Early hominins, australopiths, were similar to most large primates in having relatively short hindlimbs for their body size. The short legs of large primates are thought to represent specialization for vertical climbing and quadrupedal stability on branches. Although this may be true, there are reasons to suspect that the evolution of short legs may also represent specialization for physical aggression. Fighting in apes is a behavior in which short legs are expected to improve performance by lowering the center of mass during bipedal stance and by increasing the leverage through which muscle forces can be applied to the ground. Among anthropoid primates, body size sexual dimorphism (SSD) and canine height sexual dimorphism (CSD) are strongly correlated with levels of male-male competition, allowing SSD and CSD to be used as indices of male-male aggression. Here I show that the evolution of hindlimb length in apes is inversely correlated with the evolution of SSD (R(2)= 0.683, P-value = 0.006) and the evolution of CSD (R(2)= 0.630, P-value = 0.013). In contrast, a significant correlation was not observed for the relationship between the evolution of hindlimb and forelimb lengths. These observations are consistent with the suggestion that selection for fighting performance has maintained relatively short hindlimbs in species of Hominoidea with high levels of male-male competition. Although australopiths were highly derived for striding bipedalism when traveling on the ground, they retained short legs compared to those of Homo for over two million years, approximately 100,000 generations. Their short legs may be indicative of persistent selection for high levels of aggression.

  3. Episodic Diversifying Selection Shaped the Genomes of Gibbon Ape Leukemia Virus and Related Gammaretroviruses

    PubMed Central

    Alfano, Niccolò; Kolokotronis, Sergios-Orestis; Tsangaras, Kyriakos; Roca, Alfred L.; Xu, Wenqin; Eiden, Maribeth V.

    2015-01-01

    ABSTRACT Gibbon ape leukemia viruses (GALVs) are part of a larger group of pathogenic gammaretroviruses present across phylogenetically diverse host species of Australasian mammals. Despite the biomedical utility of GALVs as viral vectors and in cancer gene therapy, full genome sequences have not been determined for all of the five identified GALV strains, nor has a comprehensive evolutionary analysis been performed. We therefore generated complete genomic sequences for each GALV strain using hybridization capture and high-throughput sequencing. The four strains of GALV isolated from gibbons formed a monophyletic clade that was closely related to the woolly monkey virus (WMV), which is a GALV strain that likely originated in a gibbon host. The GALV-WMV clade in turn formed a sister group to the koala retroviruses (KoRVs). Genomic signatures of episodic diversifying selection were detected among the gammaretroviruses with concentration in the env gene across the GALV strains that were particularly oncogenic and KoRV strains that were potentially exogenous, likely reflecting their adaptation to the host immune system. In vitro studies involving vectors chimeric between GALV and KoRV-B established that variable regions A and B of the surface unit of the envelope determine which receptor is used by a viral strain to enter host cells. IMPORTANCE The gibbon ape leukemia viruses (GALVs) are among the most medically relevant retroviruses due to their use as viral vectors for gene transfer and in cancer gene therapy. Despite their importance, full genome sequences have not been determined for the majority of primate isolates, nor has comprehensive evolutionary analysis been performed, despite evidence that the viruses are facing complex selective pressures associated with cross-species transmission. Using hybridization capture and high-throughput sequencing, we report here the full genome sequences of all the GALV strains and demonstrate that diversifying selection is

  4. Tracking the displacement of objects: a series of tasks with great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, and Pongo pygmaeus) and young children (Homo sapiens).

    PubMed

    Barth, Jochen; Call, Josep

    2006-07-01

    The authors administered a series of object displacement tasks to 24 great apes and 24 30-month-old children (Homo sapiens). Objects were placed under 1 or 2 of 3 cups by visible or invisible displacements. The series included 6 tasks: delayed response, inhibition test, A not B, rotations, transpositions, and object permanence. Apes and children solved most tasks performing at comparable levels except in the transposition task, in which apes performed better than children. Ape species performed at comparable levels in all tasks except in single transpositions, in which chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) performed better than gorillas (Gorilla gorilla) and orangutans (Pongo pygmeaus). All species found nonadjacent trials and rotations especially difficult. The number of elements that changed locations, the type of displacement, and having to inhibit predominant reaching responses were factors that negatively affected the subjects' performance.

  5. Astragalus and Paeoniae Radix Rubra extract (APE) inhibits hepatic stellate cell activation by modulating transforming growth factor-β/smad pathway

    PubMed Central

    HUANG, WEIJUAN; LI, LIN; TIAN, XIAOPENG; YAN, JINJIN; YANG, XINZHENG; WANG, XINLONG; LIAO, GUOZHEN; QIU, GENQUAN

    2015-01-01

    Previous studies have shown that Astragalus and Paeoniae Radix Rubra extract (APE) is capable of protecting against liver fibrosis in rats. The hypothesis of the present study was that APE exerts its anti-fibrotic effect by mediating the transforming growth factor β (TGF-β)/Smad signaling pathway. In order to investigate this hypothesis, a series of assays were designed to detect the effects of APE on cell proliferation, cell invasion and the activation of hepatic stellate cells (HSCs). In addition, the effects of APE on the TGF-β/Smad signaling pathway were explored, with the aim of elucidating the underlying mechanisms. HSCs were initially isolated from normal rat liver. A number of assays were then employed in order to evaluate the effects of APE on the function of these cells. Cell proliferation was investigated using an MTT assay and cell invasion was observed with the use of transwell invasion chambers. Collagen synthesis was measured with a 3H-proline incorporation assay and expression of α-smooth muscle actin was used to determine the extent of HSC activation. Protein expression induced by TGF-β1 in HSCs was investigated by western blot and immunofluorescence analyses. Plasminogen activator inhibitor type1 (PAI-1) and urokinase-type plasminogen activator (uPA) transcriptional activity was measured using reverse transcription polymerase chain reaction. The results demonstrated that APE (5–80 μg/ml) significantly inhibited fetal bovine serum-induced cell proliferation in a dose-dependent manner. Cell invasion and activation of HSCs induced by TGF-β1 were disrupted by treatment with APE in a dose-dependent manner. TGF-β1 was observed to increase the phosphorylation of Smad2/3, while APE administered at higher doses produced inhibitory effects on Smad2/3 phosphorylation. In addition, administration of APE abrogated the TGF-β1-induced reduction in Smad-7 expression in a dose-dependent manner. The results further indicated that APE treatment not only

  6. Conserved structural chemistry for incision activity in structurally non-homologous apurinic/apyrimidinic endonuclease APE1 and endonuclease IV DNA repair enzymes.

    SciTech Connect

    Tsutakawa, Susan E.; Shin, David S.; Mol, Clifford D.; Izum, Tadahide; Arvai, Andrew S.; Mantha, Anil K.; Szczesny, Bartosz; Ivanov, Ivaylo N.; Hosfield, David J.; Maiti, Buddhadev; Pique, Mike E.; Frankel, Kenneth A.; Hitomi, Kenichi; Cunningham, Richard P.; Mitra, Sankar; Tainer, John A.

    2013-03-22

    Non-coding apurinic/apyrimidinic (AP) sites in DNA form spontaneously and as DNA base excision repair intermediates are the most common toxic and mutagenic in vivo DNA lesion. For repair, AP sites must be processed by 5' AP endonucleases in initial stages of base repair. Human APE1 and bacterial Nfo represent the two conserved 5' AP endonuclease families in the biosphere; they both recognize AP sites and incise the phosphodiester backbone 5' to the lesion, yet they lack similar structures and metal ion requirements. Here, we determined and analyzed crystal structures of a 2.4 ? resolution APE1-DNA product complex with Mg(2+) and a 0.92 Nfo with three metal ions. Structural and biochemical comparisons of these two evolutionarily distinct enzymes characterize key APE1 catalytic residues that are potentially functionally similar to Nfo active site components, as further tested and supported by computational analyses. We observe a magnesium-water cluster in the APE1 active site, with only Glu-96 forming the direct protein coordination to the Mg(2+). Despite differences in structure and metal requirements of APE1 and Nfo, comparison of their active site structures surprisingly reveals strong geometric conservation of the catalytic reaction, with APE1 catalytic side chains positioned analogously to Nfo metal positions, suggesting surprising functional equivalence between Nfo metal ions and APE1 residues. The finding that APE1 residues are positioned to substitute for Nfo metal ions is supported by the impact of mutations on activity. Collectively, the results illuminate the activities of residues, metal ions, and active site features for abasic site endonucleases.

  7. Repetitive sequences originating from the centromere constitute large-scale heterochromatin in the telomere region in the siamang, a small ape

    PubMed Central

    Koga, A; Hirai, Y; Hara, T; Hirai, H

    2012-01-01

    Chromosomes of the siamang Symphalangus syndactylus (a small ape) carry large-scale heterochromatic structures at their ends. These structures look similar, by chromosome C-banding, to chromosome-end heterochromatin found in chimpanzee, bonobo and gorilla (African great apes), of which a major component is tandem repeats of 32-bp-long, AT-rich units. In the present study, we identified repetitive sequences that are a major component of the siamang heterochromatin. Their repeat units are 171 bp in length, and exhibit sequence similarity to alpha satellite DNA, a major component of the centromeres in primates. Thus, the large-scale heterochromatic structures have different origins between the great apes and the small ape. The presence of alpha satellite DNA in the telomere region has previously been reported in the white-cheeked gibbon Nomascus leucogenys, another small ape species. There is, however, a difference in the size of the telomere-region alpha satellite DNA, which is far larger in the siamang. It is not known whether the sequences of these two species (of different genera) have a common origin because the phylogenetic relationship of genera within the small ape family is still not clear. Possible evolutionary scenarios are discussed. PMID:22669075

  8. Trans-complementation by human apurinic endonuclease (Ape) of hypersensitivity to DNA damage and spontaneous mutator phenotype in apn1-yeast.

    PubMed Central

    Wilson, D M; Bennett, R A; Marquis, J C; Ansari, P; Demple, B

    1995-01-01

    Abasic (AP) sites in DNA are potentially lethal and mutagenic. 'Class II' AP endonucleases initiate the repair of these and other DNA lesions. In yeast, the predominant enzyme of this type is Apn1, and its elimination sensitizes the cells to killing by simple alkylating agents or oxidants, and raises the rate of spontaneous mutation. We investigated the ability of the major human class II AP endonuclease, Ape, which is structurally unrelated to Apn1, to replace the yeast enzyme in vivo. Confocal immunomicroscopy studies indicate that approximately 25% of the Ape expressed in yeast is present in the nucleus. High-level Ape expression corresponding to approximately 7000 molecules per nucleus, equal to the normal Apn1 copy number, restored resistance to methyl methanesulfonate to near wild-type levels in Apn1-deficient (apn1-) yeast. Ape expression in apn1- yeast provided little protection against H2O2 challenges, consistent with the weak 3'-repair diesterase activity of the human enzyme. Ape expression at approximately 2000 molecules per nucleus reduced the spontaneous mutation rate of apn1- yeast to that seen for wild-type cells. Because Ape has a powerful AP endonuclease but weak 3'-diesterase activity, these findings indicate that endogenously generated AP sites can drive spontaneous mutagenesis. Images PMID:8559661

  9. Detailed comparative anatomy of the extrinsic cardiac nerve plexus and postnatal reorganization of the cardiac position and innervation in the great apes: orangutans, gorillas, and chimpanzees.

    PubMed

    Kawashima, Tomokazu; Sato, Fumi

    2012-03-01

    To speculate how the extrinsic cardiac nerve plexus (ECNP) evolves phyletically and ontogenetically within the primate lineage, we conducted a comparative anatomical study of the ECNP, including an imaging examination in the great apes using 20 sides from 11 bodies from three species and a range of postnatal stages from newborns to mature adults. Although the position of the middle cervical ganglion (MG) in the great apes tended to be relatively lower than that in humans, the morphology of the ECNP in adult great apes was almost consistent with that in adult humans but essentially different from that in the lesser apes or gibbons. Therefore, the well-argued anatomical question of when did the MG acquire communicating branches with the spinal cervical nerves and appear constantly in all sympathetic cardiac nerves during primate evolution is clearly considered to be after the great apes and gibbons split. Moreover, a horizontal four-chambered heart and a lifted cardiac apex with a relatively large volume in newborn great apes rapidly changed its position downward, as seen in humans during postnatal growth and was associated with a reduction in the hepatic volume by imaging diagnosis and gross anatomy. In addition, our observation using a range of postnatal stages exhibits that two sympathetic ganglia, the middle cervical and cervicothoracic ganglia, differed between the early and later postnatal stages. Copyright © 2011 Wiley Periodicals, Inc.

  10. Repetitive sequences originating from the centromere constitute large-scale heterochromatin in the telomere region in the siamang, a small ape.

    PubMed

    Koga, A; Hirai, Y; Hara, T; Hirai, H

    2012-09-01

    Chromosomes of the siamang Symphalangus syndactylus (a small ape) carry large-scale heterochromatic structures at their ends. These structures look similar, by chromosome C-banding, to chromosome-end heterochromatin found in chimpanzee, bonobo and gorilla (African great apes), of which a major component is tandem repeats of 32-bp-long, AT-rich units. In the present study, we identified repetitive sequences that are a major component of the siamang heterochromatin. Their repeat units are 171 bp in length, and exhibit sequence similarity to alpha satellite DNA, a major component of the centromeres in primates. Thus, the large-scale heterochromatic structures have different origins between the great apes and the small ape. The presence of alpha satellite DNA in the telomere region has previously been reported in the white-cheeked gibbon Nomascus leucogenys, another small ape species. There is, however, a difference in the size of the telomere-region alpha satellite DNA, which is far larger in the siamang. It is not known whether the sequences of these two species (of different genera) have a common origin because the phylogenetic relationship of genera within the small ape family is still not clear. Possible evolutionary scenarios are discussed.

  11. Transferability of HIV by arthropods supports the hypothesis about transmission of the virus from apes to man

    NASA Astrophysics Data System (ADS)

    Eigen, Manfred; Kloft, Werner; Brandner, Gerhard

    2002-03-01

    The primate Pan troglodytes troglodytes, a chimpanzee subspecies, has recently been defined as a natural animal host of the human immunodeficiency virus (HIV). Apes are traditionally hunted in Africa and are offered for sale in open-air meat markets. The bloody carcasses are regularly covered with blood-feeding flies, amongst them possibly the stable fly (Stomoxys calcitrans L.), a cosmopolitically occurring biting fly. This fly is the effective vector for the retrovirus causing equine leukemia. According to laboratory experiments, the infectivity of ingested HIV is not reduced in the regurgitates of this fly. These findings are combined to explain the mechanism for a possible primary transmission of HIV from ape to man.

  12. Transferability of HIV by arthropods supports the hypothesis about transmission of the virus from apes to man.

    PubMed

    Eigen, Manfred; Kloft, Werner J; Brandner, Gerhard

    2002-04-01

    The primate Pan troglodytes troglodytes, a chimpanzee subspecies, has recently been defined as a natural animal host of the human immunodeficiency virus (HIV). Apes are traditionally hunted in Africa and are offered for sale in open-air meat markets. The bloody carcasses are regularly covered with blood-feeding flies, amongst them possibly the stable fly (Stomoxvs calcitrans L.). a cosmopolitically occurring biting fly. This fly is the effective vector for the retrovirus causing equine infectious anemia [corrected]. According to laboratory experiments, the infectivity of ingested HIV is not reduced in the regurgitates of this fly. These findings are combined to explain the mechanism for a possible primary transmission of HIV from ape to man.

  13. Association of the polymorphism of APE1 gene with the risk of prostate cancer in Chinese Han population.

    PubMed

    Jing, Bao; Wang, Juan; Chang, Wen-Liang; Li, Bo; Chen, Jing; Niu, Yuan-Jie

    2013-01-01

    DNA damage, caused by numerous carcinogens, contributes to the increased risk of different types of cancer. The base excision repair (BER) pathway including the apurinic/apyrimidic endonuclease (APE1, also known as APEX1) gene plays an important role in preventing the accumulation of DNA damage and maintaining genomic stability. The aim of the present study is to determine whether polymorphisms of APE1 are associated with the risk of prostate cancer (PCa) in the Chinese Han population. This study consisted of 198 patients with PCa and 156 healthy controls. The polymorphisms of APE1, Asp148Glu (rs1130409) and -141T/G (rs1760944) were determined by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The genotypic distributions of the two polymorphisms in controls were in Hardy-Weinberg equilibrium (p = 0.92 and p = 0.83, respectively). Logistic regression analysis indicated that the -141GG genotype was significantly associated with a decreased risk of PCa compared with the -141TT genotype (p = 0.03; OR 0.49; 95% CI 0.26 - 0.92). The G allele was also significantly associated with a reduced risk of PCa compared with the T allele (p = 0.02; OR 0.71; 95% CI 0.52 - 0.96). However, no association between Asp148Glu polymorphism and the risk of PCa was found. The -141GG genotype and G allele of the APE1 gene are associated with a decreased risk of PCa in the Chinese Han population.

  14. Hindlimb muscle architecture in non-human great apes and a comparison of methods for analysing inter-species variation

    PubMed Central

    Myatt, Julia P; Crompton, Robin H; Thorpe, Susannah K S

    2011-01-01

    By relating an animal's morphology to its functional role and the behaviours performed, we can further develop our understanding of the selective factors and constraints acting on the adaptations of great apes. Comparison of muscle architecture between different ape species, however, is difficult because only small sample sizes are ever available. Further, such samples are often comprised of different age–sex classes, so studies have to rely on scaling techniques to remove body mass differences. However, the reliability of such scaling techniques has been questioned. As datasets increase in size, more reliable statistical analysis may eventually become possible. Here we employ geometric and allometric scaling techniques, and ancovas (a form of general linear model, GLM) to highlight and explore the different methods available for comparing functional morphology in the non-human great apes. Our results underline the importance of regressing data against a suitable body size variable to ascertain the relationship (geometric or allometric) and of choosing appropriate exponents by which to scale data. ancova models, while likely to be more robust than scaling for species comparisons when sample sizes are high, suffer from reduced power when sample sizes are low. Therefore, until sample sizes are radically increased it is preferable to include scaling analyses along with ancovas in data exploration. Overall, the results obtained from the different methods show little significant variation, whether in muscle belly mass, fascicle length or physiological cross-sectional area between the different species. This may reflect relatively close evolutionary relationships of the non-human great apes; a universal influence on morphology of generalised orthograde locomotor behaviours or, quite likely, both. PMID:21507000

  15. MIL-STD-398 Acceptance Test of Ammunition Peculiar Equipment (APE) 1974E002 Continuity Kit for M76 Grenade

    DTIC Science & Technology

    1990-02-01

    SMcAc.DEN C, 0 ! ). Savanna, IL 61074-9639 US ARMY ARMAMENT MUNITIONS EVALUATION DIVISION CHEMICAL COMMAND US ARMY DEFENSE AMMUNITION SAVANNA, ILLINOIS...USADACS). Evaluation Division (SMCAC-DEV), was tasked by the Equipment Division (SMCAC-DEN) to test the Ammunition Peculiar Equipment (APE) 1974E002...Equipment Division and approved by U.S. Army Materiel Command Field Safety Activity (AMCFSA). Charlestown, IN. The test plan defines the Maximum Credible

  16. Modern African ape populations as genetic and demographic models of the last common ancestor of humans, chimpanzees, and gorillas.

    PubMed

    Jensen-Seaman, M I; Deinard, A S; Kidd, K K

    2001-01-01

    In order to fully understand human evolutionary history through the use of molecular data, it is essential to include our closest relatives as a comparison. We provide here estimates of nucleotide diversity and effective population size of modern African ape species using data from several independent noncoding nuclear loci, and use these estimates to make predictions about the nature of the ancestral population that eventually gave rise to the living species of African apes, including humans. Chimpanzees, bonobos, and gorillas possess two to three times more nucleotide diversity than modern humans. We hypothesize that the last common ancestor (LCA) of these species had an effective population size more similar to modern apes than modern humans. In addition, estimated dates for the divergence of the Homo, Pan, and Gorilla lineages suggest that the LCA may have had stronger geographic structuring to its mtDNA than its nuclear DNA, perhaps indicative of strong female philopatry or a dispersal system analogous to gorillas, where females disperse only short distances from their natal group. Synthesizing different classes of data, and the inferences drawn from them, allows us to predict some of the genetic and demographic properties of the LCA of humans, chimpanzees, and gorillas.

  17. Remembering in tool-use tasks in children and apes: the role of the information at encoding.

    PubMed

    Martin-Ordas, Gema; Atance, Cristina M; Call, Josep

    2014-01-01

    Providing adults with relevant information (knowledge that they will be tested at some future time) increases motivation to remember. Research has shown that it is more effective to have this information prior to, rather than after, an encoding phase. We investigated this effect in apes and children in the context of tool-use tasks. In Experiment 1 we presented chimpanzees, orangutans, and bonobos with two tool-use tasks and three different two-tool sets. We had two conditions: prospective (PP) and retrospective (RP). In the PP subjects were shown the task that they would have to solve before they were shown the tools with which they could solve it. In the RP this order was reversed. Apes remembered the location of the useful tool better in the PP than in the RP. In Experiment 2 we presented 3- and 4-year-olds with the same conditions. Both age groups remembered the location of the correct tool in the PP, but only the 4-year-olds did so in the RP. Thus providing apes and preschool children with relevant information prior to, rather than after, the encoding phase enhances memory. These results have important implications for the understanding of the evolution of memory in general, and encoding mechanisms in particular.

  18. Adenovirus and Herpesvirus Diversity in Free-Ranging Great Apes in the Sangha Region of the Republic of Congo

    PubMed Central

    Seimon, Tracie A.; Olson, Sarah H.; Lee, Kerry Jo; Rosen, Gail; Ondzie, Alain; Cameron, Kenneth; Reed, Patricia; Anthony, Simon J.; Joly, Damien O.; McAloose, Denise; Lipkin, W. Ian

    2015-01-01

    Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region. PMID:25781992

  19. Great apes' (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) understanding of tool functional properties after limited experience.

    PubMed

    Herrmann, Esther; Wobber, Victoria; Call, Josep

    2008-05-01

    Primates' understanding of tool functionality has been investigated extensively using a paradigm in which subjects are presented with a tool that they must use to obtain an out-of-reach reward. After being given experience on an initial problem, monkeys can transfer their skill to tools of different shapes while ignoring irrelevant tool changes (e.g., color). In contrast, monkeys without initial training perform poorly on the same tasks. Compared to most monkeys, great apes show a clear propensity for tool using and may not require as much experience to succeed on tool functionality tasks. We investigated this question by presenting 171 apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, and Pongo pygmaeus) with several tool-use problems without giving them initial training or familiarizing them with the test materials. Apes succeeded without experience, but only on problems based on basic properties such as the reward being supported by an object. However, only minimal experience was sufficient to allow them to quickly improve their performance on more complex problems in which the reward was not in contact with the tool.

  20. A comparative volumetric analysis of the amygdaloid complex and basolateral division in the human and ape brain.

    PubMed

    Barger, Nicole; Stefanacci, Lisa; Semendeferi, Katerina

    2007-11-01

    The amygdaloid complex functions to facilitate effective appraisal of the social environment and is an essential component of the neural systems subserving social behavior. Despite its critical role in mediating social interaction, the amygdaloid complex has not attracted the same attention as the isocortex in most evolutionary analyses. We performed a comparative analysis of the amygdaloid complex in the hominoids to address the lack of comparative information available for this structure in the hominoid brain. We demarcated the amygdaloid complex and the three nuclei constituting its basolateral division, the lateral, basal, and accessory basal nuclei, in 12 histological series representing all six hominoid species. The volumes obtained for these areas were subjected to allometric analyses to determine whether any species deviated from expected values based on the other hominoids. Differences between groups were addressed using nonparametric comparisons of means. The human lateral nucleus was larger than predicted for an ape of human brain size and occupied the majority of the basolateral division, whereas the basal nucleus was the largest of the basolateral nuclei in all ape species. In orangutans the amygdala and basolateral division were smaller than in the African apes. While the gorilla had a smaller than predicted lateral nucleus, its basal and accessory basal nuclei were larger than predicted. These differences may reflect volumetric changes occurring in interconnected cortical areas, specifically the temporal lobe and orbitofrontal cortex, which also subserve social behavior and cognition, suggesting that this system may be acted upon in hominoid and hominid evolution.

  1. Ravens, New Caledonian crows and jackdaws parallel great apes in motor self-regulation despite smaller brains.

    PubMed

    Kabadayi, Can; Taylor, Lucy A; von Bayern, Auguste M P; Osvath, Mathias

    2016-04-01

    Overriding motor impulses instigated by salient perceptual stimuli represent a fundamental inhibitory skill. Such motor self-regulation facilitates more rational behaviour, as it brings economy into the bodily interaction with the physical and social world. It also underlies certain complex cognitive processes including decision making. Recently, MacLean et al. (MacLean et al. 2014 Proc. Natl Acad. Sci. USA 111, 2140-2148. (doi:10.1073/pnas.1323533111)) conducted a large-scale study involving 36 species, comparing motor self-regulation across taxa. They concluded that absolute brain size predicts level of performance. The great apes were most successful. Only a few of the species tested were birds. Given birds' small brain size-in absolute terms-yet flexible behaviour, their motor self-regulation calls for closer study. Corvids exhibit some of the largest relative avian brain sizes-although small in absolute measure-as well as the most flexible cognition in the animal kingdom. We therefore tested ravens, New Caledonian crows and jackdaws in the so-called cylinder task. We found performance indistinguishable from that of great apes despite the much smaller brains. We found both absolute and relative brain volume to be a reliable predictor of performance within Aves. The complex cognition of corvids is often likened to that of great apes; our results show further that they share similar fundamental cognitive mechanisms.

  2. Adenovirus and herpesvirus diversity in free-ranging great apes in the Sangha region of the Republic Of Congo.

    PubMed

    Seimon, Tracie A; Olson, Sarah H; Lee, Kerry Jo; Rosen, Gail; Ondzie, Alain; Cameron, Kenneth; Reed, Patricia; Anthony, Simon J; Joly, Damien O; Karesh, William B; McAloose, Denise; Lipkin, W Ian

    2015-01-01

    Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region.

  3. Ravens, New Caledonian crows and jackdaws parallel great apes in motor self-regulation despite smaller brains

    PubMed Central

    Kabadayi, Can; Taylor, Lucy A.; von Bayern, Auguste M. P.; Osvath, Mathias

    2016-01-01

    Overriding motor impulses instigated by salient perceptual stimuli represent a fundamental inhibitory skill. Such motor self-regulation facilitates more rational behaviour, as it brings economy into the bodily interaction with the physical and social world. It also underlies certain complex cognitive processes including decision making. Recently, MacLean et al. (MacLean et al. 2014 Proc. Natl Acad. Sci. USA 111, 2140–2148. (doi:10.1073/pnas.1323533111)) conducted a large-scale study involving 36 species, comparing motor self-regulation across taxa. They concluded that absolute brain size predicts level of performance. The great apes were most successful. Only a few of the species tested were birds. Given birds' small brain size—in absolute terms—yet flexible behaviour, their motor self-regulation calls for closer study. Corvids exhibit some of the largest relative avian brain sizes—although small in absolute measure—as well as the most flexible cognition in the animal kingdom. We therefore tested ravens, New Caledonian crows and jackdaws in the so-called cylinder task. We found performance indistinguishable from that of great apes despite the much smaller brains. We found both absolute and relative brain volume to be a reliable predictor of performance within Aves. The complex cognition of corvids is often likened to that of great apes; our results show further that they share similar fundamental cognitive mechanisms. PMID:27152224

  4. Patterns of C-heterochromatin and telomeric DNA in two representative groups of small apes, the genera Hylobates and Symphalangus.

    PubMed

    Wijayanto, Hery; Hirai, Yuriko; Kamanaka, Yosirou; Katho, Akira; Sajuthi, Dondin; Hirai, Hirohisa

    2005-01-01

    The course of chromosome evolution in small apes is still not clear, though painting analyses have opened the way for elucidating the puzzle. Even the C-banding pattern of the lar-group of gibbons (the genus Hylobates) is not clarified yet, although our previous studies suggested that lar-group gibbons have a unique C-banding pattern. We therefore made observations to establish C-banded karyotypes of the agile gibbons included in the lar-group. The data were compared with those of siamangs (the genus Symphalangus), which carry distinctive C-bands, to determine the chromosomal patterns in each group. C-banded chromosomes of agile gibbons showed several terminal, interstitial and paracentric bands, whose patterns are specific for each chromosome, whereas the C-bands of siamangs were located only at the terminal and centromeric regions in most chromosomes. Moreover, the C-bands of agile gibbons and siamangs were shown to be G+C-rich and A+T-rich DNA, respectively, by DAPI/C-band sequential staining. Additionally, PRINS labelling with a telomere primer revealed that agile gibbons have telomeric DNA only at chromosome ends where there is no C-band (non-telomeric heterochromatin), whereas the telomeric DNA of siamangs is located in the terminal C-banded regions (telomeric heterochromatin). Although the evolutionary mechanisms in small apes are still unknown, C-banding patterns and distribution of telomeric DNA sequences should provide valuable data to deduce the evolutionary pathways of small apes.

  5. Mitochondrial evidence for multiple radiations in the evolutionary history of small apes

    PubMed Central

    2010-01-01

    Background Gibbons or small apes inhabit tropical and subtropical rain forests in Southeast Asia and adjacent regions, and are, next to great apes, our closest living relatives. With up to 16 species, gibbons form the most diverse group of living hominoids, but the number of taxa, their phylogenetic relationships and their phylogeography is controversial. To further the discussion of these issues we analyzed the complete mitochondrial cytochrome b gene from 85 individuals representing all gibbon species, including most subspecies. Results Based on phylogenetic tree reconstructions, several monophyletic clades were detected, corresponding to genera, species and subspecies. A significantly supported branching pattern was obtained for members of the genus Nomascus but not for the genus Hylobates. The phylogenetic relationships among the four genera were also not well resolved. Nevertheless, the new data permitted the estimation of divergence ages for all taxa for the first time and showed that most lineages emerged during four short time periods. In the first, between ~6.7 and ~8.3 mya, the four gibbon genera diverged from each other. In the second (~3.0 - ~3.9 mya) and in the third period (~1.3 - ~1.8 mya), Hylobates and Hoolock differentiated. Finally, between ~0.5 and ~1.1 mya, Hylobates lar diverged into subspecies. In contrast, differentiation of Nomascus into species and subspecies was a continuous and prolonged process lasting from ~4.2 until ~0.4 mya. Conclusions Although relationships among gibbon taxa on various levels remain unresolved, the present study provides a more complete view of the evolutionary and biogeographic history of the hylobatid family, and a more solid genetic basis for the taxonomic classification of the surviving taxa. We also show that mtDNA constitutes a useful marker for the accurate identification of individual gibbons, a tool which is urgently required to locate hunting hotspots and select individuals for captive breeding programs

  6. Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia).

    PubMed

    Alfano, Niccolò; Michaux, Johan; Morand, Serge; Aplin, Ken; Tsangaras, Kyriakos; Löber, Ulrike; Fabre, Pierre-Henri; Fitriana, Yuli; Semiadi, Gono; Ishida, Yasuko; Helgen, Kristofer M; Roca, Alfred L; Eiden, Maribeth V; Greenwood, Alex D

    2016-09-15

    Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (Melomys burtoni) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV- and GALV-like sequences, using hybridization capture and high-throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies of Melomys burtoni from Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the Indonesian M. burtoni subsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV in M. burtoni provides further evidence that M. burtoni, and potentially other lineages within the widespread subfamily Murinae, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution of M. burtoni, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents. Gibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross-species transfer from an intermediate host whose range

  7. Episodic Diversifying Selection Shaped the Genomes of Gibbon Ape Leukemia Virus and Related Gammaretroviruses.

    PubMed

    Alfano, Niccolò; Kolokotronis, Sergios-Orestis; Tsangaras, Kyriakos; Roca, Alfred L; Xu, Wenqin; Eiden, Maribeth V; Greenwood, Alex D

    2015-12-04

    Gibbon ape leukemia viruses (GALVs) are part of a larger group of pathogenic gammaretroviruses present across phylogenetically diverse host species of Australasian mammals. Despite the biomedical utility of GALVs as viral vectors and in cancer gene therapy, full genome sequences have not been determined for all of the five identified GALV strains, nor has a comprehensive evolutionary analysis been performed. We therefore generated complete genomic sequences for each GALV strain using hybridization capture and high-throughput sequencing. The four strains of GALV isolated from gibbons formed a monophyletic clade that was closely related to the woolly monkey virus (WMV), which is a GALV strain that likely originated in a gibbon host. The GALV-WMV clade in turn formed a sister group to the koala retroviruses (KoRVs). Genomic signatures of episodic diversifying selection were detected among the gammaretroviruses with concentration in the env gene across the GALV strains that were particularly oncogenic and KoRV strains that were potentially exogenous, likely reflecting their adaptation to the host immune system. In vitro studies involving vectors chimeric between GALV and KoRV-B established that variable regions A and B of the surface unit of the envelope determine which receptor is used by a viral strain to enter host cells. The gibbon ape leukemia viruses (GALVs) are among the most medically relevant retroviruses due to their use as viral vectors for gene transfer and in cancer gene therapy. Despite their importance, full genome sequences have not been determined for the majority of primate isolates, nor has comprehensive evolutionary analysis been performed, despite evidence that the viruses are facing complex selective pressures associated with cross-species transmission. Using hybridization capture and high-throughput sequencing, we report here the full genome sequences of all the GALV strains and demonstrate that diversifying selection is acting on them

  8. Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia)

    PubMed Central

    Alfano, Niccolò; Michaux, Johan; Morand, Serge; Aplin, Ken; Tsangaras, Kyriakos; Löber, Ulrike; Fabre, Pierre-Henri; Fitriana, Yuli; Semiadi, Gono; Ishida, Yasuko; Helgen, Kristofer M.; Roca, Alfred L.; Eiden, Maribeth V.

    2016-01-01

    ABSTRACT Gibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (Melomys burtoni) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV- and GALV-like sequences, using hybridization capture and high-throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies of Melomys burtoni from Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the Indonesian M. burtoni subsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV in M. burtoni provides further evidence that M. burtoni, and potentially other lineages within the widespread subfamily Murinae, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution of M. burtoni, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents. IMPORTANCE Gibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross-species transfer from an intermediate

  9. NT-16NANOPARTICLE-MEDIATED DELIVERY OF ANTI-Ape1 siRNA SENSITIZES PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY BY INHIBITING DNA REPAIR

    PubMed Central

    Kievit, Forrest; Stephen, Zachary; Wang, Kui; Dayringer, Christopher; Ellenbogen, Richard; Silber, John; Zhang, Miqin

    2014-01-01

    Pediatric brain tumors are the leading cause of death in children, and survival is frequently accompanied by one or more radiation-induced adverse developmental and psychosocial sequelae. Radiotherapy (RT) is an integral component of the treatment for medulloblastoma (MB) and the only effective adjuvant therapy for ependymoma (EP). Therefore, there is an urgent need to develop strategies to enhance the tumoricidal action of RT while sparing adjacent normal tissue. The multifunctional DNA repair protein Ape1/Ref-1 has been implicated in conferring radiation resistance in pediatric brain tumors. However, inhibiting Ape1 activity in the clinic has been hindered by the lack of safe and effective drugs and siRNA delivery vehicles. We have previously developed a nanoparticle that can deliver siRNA specifically to brain tumors for efficient knockdown of GFP. Here, we aimed to deliver siRNA against Ape1 to improve tumor cell kill after RT. Nanoparticles were loaded with siApe1, or siGFP as a control, and used to treat UW228 (MB) and Res196 (EP) cells. Ape1 expression levels were measured using PCR and Western blot, and the abasic endonuclease activity of Ape1 was determined using an Ape activity assay. Cells were then treated with 137Cs-γ-rays and cell survival monitored using clonogenic assays. DNA repair in cells was assessed though quantification of abasic sites, and resulting double-strand breaks were imaged by γH2AX foci immunostaining. We found that nanoparticle-mediated siApe1 delivery reduced Ape1 expression and activity by greater than 80%. This diminished the shoulder of resistance in survival curves decreasing survival to ∼50% at 1 Gy, and was accompanied by inhibition of DNA repair. Sensitization was specific to abasic site generating treatments as response to paclitaxel was not affected. Therefore, siApe1 loaded nanoparticles may help enhance the therapeutic effect of RT in pediatric brain tumor patients by inhibiting DNA repair.

  10. Role of the DNA Base Excision Repair Protein, APE1 in Cisplatin, Oxaliplatin, or Carboplatin Induced Sensory Neuropathy

    PubMed Central

    Kelley, Mark R.; Jiang, Yanlin; Guo, Chunlu; Reed, April; Meng, Hongdi; Vasko, Michael R.

    2014-01-01

    Although chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of platinum drugs, the mechanisms of this toxicity remain unknown. Previous work in our laboratory suggests that cisplatin-induced CIPN is secondary to DNA damage which is susceptible to base excision repair (BER). To further examine this hypothesis, we studied the effects of cisplatin, oxaliplatin, and carboplatin on cell survival, DNA damage, ROS production, and functional endpoints in rat sensory neurons in culture in the absence or presence of reduced expression of the BER protein AP endonuclease/redox factor-1 (APE1). Using an in situ model of peptidergic sensory neuron function, we examined the effects of the platinum drugs on hind limb capsaicin-evoked vasodilatation. Exposing sensory neurons in culture to the three platinum drugs caused a concentration-dependent increase in apoptosis and cell death, although the concentrations of carboplatin were 10 fold higher than cisplatin. As previously observed with cisplatin, oxaliplatin and carboplatin also increased DNA damage as indicated by an increase in phospho-H2AX and reduced the capsaicin-evoked release of CGRP from neuronal cultures. Both cisplatin and oxaliplatin increased the production of ROS as well as 8-oxoguanine DNA adduct levels, whereas carboplatin did not. Reducing levels of APE1 in neuronal cultures augmented the cisplatin and oxaliplatin induced toxicity, but did not alter the effects of carboplatin. Using an in vivo model, systemic injection of cisplatin (3 mg/kg), oxaliplatin (3 mg/kg), or carboplatin (30 mg/kg) once a week for three weeks caused a decrease in capsaicin-evoked vasodilatation, which was delayed in onset. The effects of cisplatin on capsaicin-evoked vasodilatation were attenuated by chronic administration of E3330, a redox inhibitor of APE1 that serendipitously enhances APE1 DNA repair activity in sensory neurons. These outcomes support the importance of the BER pathway, and particularly APE

  11. The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2

    PubMed Central

    Ventura, Mario; Catacchio, Claudia R.; Sajjadian, Saba; Vives, Laura; Sudmant, Peter H.; Marques-Bonet, Tomas; Graves, Tina A.; Wilson, Richard K.; Eichler, Evan E.

    2012-01-01

    Chimpanzee and gorilla chromosomes differ from human chromosomes by the presence of large blocks of subterminal heterochromatin thought to be composed primarily of arrays of tandem satellite sequence. We explore their sequence composition and organization and show a complex organization composed of specific sets of segmental duplications that have hyperexpanded in concert with the formation of subterminal satellites. These regions are highly copy number polymorphic between and within species, and copy number differences involving hundreds of copies can be accurately estimated by assaying read-depth of next-generation sequencing data sets. Phylogenetic and comparative genomic analyses suggest that the structures have arisen largely independently in the two lineages with the exception of a few seed sequences present in the common ancestor of humans and African apes. We propose a model where an ancestral human-chimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. Our findings highlight the complex interplay between duplicated sequences and chromosomal rearrangements that rapidly alter the cytogenetic landscape in a short period of evolutionary time. PMID:22419167

  12. The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2.

    PubMed

    Ventura, Mario; Catacchio, Claudia R; Sajjadian, Saba; Vives, Laura; Sudmant, Peter H; Marques-Bonet, Tomas; Graves, Tina A; Wilson, Richard K; Eichler, Evan E

    2012-06-01

    Chimpanzee and gorilla chromosomes differ from human chromosomes by the presence of large blocks of subterminal heterochromatin thought to be composed primarily of arrays of tandem satellite sequence. We explore their sequence composition and organization and show a complex organization composed of specific sets of segmental duplications that have hyperexpanded in concert with the formation of subterminal satellites. These regions are highly copy number polymorphic between and within species, and copy number differences involving hundreds of copies can be accurately estimated by assaying read-depth of next-generation sequencing data sets. Phylogenetic and comparative genomic analyses suggest that the structures have arisen largely independently in the two lineages with the exception of a few seed sequences present in the common ancestor of humans and African apes. We propose a model where an ancestral human-chimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. Our findings highlight the complex interplay between duplicated sequences and chromosomal rearrangements that rapidly alter the cytogenetic landscape in a short period of evolutionary time.

  13. Lineage-Specific Gene Duplication and Loss in Human and Great Ape Evolution

    PubMed Central

    MacLaren, Erik; Marshall, Kriste; Hahn, Gretchen; Meltesen, Lynne; Brenton, Matthew; Hink, Raquel; Burgers, Sonya; Hernandez-Boussard, Tina; Karimpour-Fard, Anis; Glueck, Deborah; McGavran, Loris; Berry, Rebecca

    2004-01-01

    Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species. PMID:15252450

  14. A unique Middle Miocene European hominoid and the origins of the great ape and human clade

    PubMed Central

    Moyà-Solà, Salvador; Alba, David M.; Almécija, Sergio; Casanovas-Vilar, Isaac; Köhler, Meike; De Esteban-Trivigno, Soledad; Robles, Josep M.; Galindo, Jordi; Fortuny, Josep

    2009-01-01

    The great ape and human clade (Primates: Hominidae) currently includes orangutans, gorillas, chimpanzees, bonobos, and humans. When, where, and from which taxon hominids evolved are among the most exciting questions yet to be resolved. Within the Afropithecidae, the Kenyapithecinae (Kenyapithecini + Equatorini) have been proposed as the sister taxon of hominids, but thus far the fragmentary and scarce Middle Miocene fossil record has hampered testing this hypothesis. Here we describe a male partial face with mandible of a previously undescribed fossil hominid, Anoiapithecus brevirostris gen. et sp. nov., from the Middle Miocene (11.9 Ma) of Spain, which enables testing this hypothesis. Morphological and geometric morphometrics analyses of this material show a unique facial pattern for hominoids. This taxon combines autapomorphic features—such as a strongly reduced facial prognathism—with kenyapithecine (more specifically, kenyapithecin) and hominid synapomorphies. This combination supports a sister-group relationship between kenyapithecins (Griphopithecus + Kenyapithecus) and hominids. The presence of both groups in Eurasia during the Middle Miocene and the retention in kenyapithecins of a primitive hominoid postcranial body plan support a Eurasian origin of the Hominidae. Alternatively, the two extant hominid clades (Homininae and Ponginae) might have independently evolved in Africa and Eurasia from an ancestral, Middle Miocene stock, so that the supposed crown-hominid synapomorphies might be homoplastic. PMID:19487676

  15. A new approach to estimate parameters of speciation models with application to apes

    PubMed Central

    Becquet, Celine; Przeworski, Molly

    2007-01-01

    How populations diverge and give rise to distinct species remains a fundamental question in evolutionary biology, with important implications for a wide range of fields, from conservation genetics to human evolution. A promising approach is to estimate parameters of simple speciation models using polymorphism data from multiple loci. Existing methods, however, make a number of assumptions that severely limit their applicability, notably, no gene flow after the populations split and no intralocus recombination. To overcome these limitations, we developed a new Markov chain Monte Carlo method to estimate parameters of an isolation-migration model. The approach uses summaries of polymorphism data at multiple loci surveyed in a pair of diverging populations or closely related species and, importantly, allows for intralocus recombination. To illustrate its potential, we applied it to extensive polymorphism data from populations and species of apes, whose demographic histories are largely unknown. The isolation-migration model appears to provide a reasonable fit to the data. It suggests that the two chimpanzee species became reproductively isolated in allopatry ∼850 Kya, while Western and Central chimpanzee populations split ∼440 Kya but continued to exchange migrants. Similarly, Eastern and Western gorillas and Sumatran and Bornean orangutans appear to have experienced gene flow since their splits ∼90 and over 250 Kya, respectively. PMID:17712021

  16. Extreme selective sweeps independently targeted the X chromosomes of the great apes

    PubMed Central

    Nam, Kiwoong; Munch, Kasper; Hobolth, Asger; Dutheil, Julien Yann; Veeramah, Krishna R.; Woerner, August E.; Hammer, Michael F.; Mailund, Thomas; Schierup, Mikkel Heide

    2015-01-01

    The unique inheritance pattern of the X chromosome exposes it to natural selection in a way that is different from that of the autosomes, potentially resulting in accelerated evolution. We perform a comparative analysis of X chromosome polymorphism in 10 great ape species, including humans. In most species, we identify striking megabase-wide regions, where nucleotide diversity is less than 20% of the chromosomal average. Such regions are found exclusively on the X chromosome. The regions overlap partially among species, suggesting that the underlying targets are partly shared among species. The regions have higher proportions of singleton SNPs, higher levels of population differentiation, and a higher nonsynonymous-to-synonymous substitution ratio than the rest of the X chromosome. We show that the extent to which diversity is reduced is incompatible with direct selection or the action of background selection and soft selective sweeps alone, and therefore, we suggest that very strong selective sweeps have independently targeted these specific regions in several species. The only genomic feature that we can identify as strongly associated with loss of diversity is the location of testis-expressed ampliconic genes, which also have reduced diversity around them. We hypothesize that these genes may be responsible for selective sweeps in the form of meiotic drive caused by an intragenomic conflict in male meiosis. PMID:25941379

  17. The nasal and paranasal architecture of the Middle Miocene ape Pierolapithecus catalaunicus (primates: Hominidae): phylogenetic implications.

    PubMed

    Pérez de Los Ríos, Miriam; Moyà-Solà, Salvador; Alba, David M

    2012-09-01

    The internal (nasal and paranasal) cranial anatomy of the Middle Miocene (11.9 Ma [millions of years ago]) great ape Pierolapithecus catalaunicus (Hominidae: Dryopithecini) is described on the basis of computed-tomography scans of the holotype specimen (IPS21350), with particular emphasis on its phylogenetic implications. Pierolapithecus displays the following characters: an anteriorly-restricted maxillary sinus that posteriorly spreads towards the ethmoidal area (thus resembling the pongine condition), although being situated well above the molar roots (as in kenyapithecins, other dryopithecins and pongines); lack of frontal sinus (a synapomorphy of derived pongines, independently acquired by both cercopithecoids and hylobatids); posteriorly-situated turbinals (as in Pongo); anteriorly-projecting nasolacrimal canal (as in Pongo); and probably stepped nasal floor with non-overlapping premaxillary-maxillary contact (as in dryopithecines and stem hominoids, although it cannot be conclusively shown due to bone damage). Overall, Pierolapithecus displays a mosaic of primitive hominid and derived pongine features that are inconsistent with this taxon being a hominine (as previously suggested). Two alternative phylogenetic interpretations are possible: Pierolapithecus may be a stem member of the Hominidae as previously suggested in its original description, or alternatively this taxon may be a stem member of the Ponginae s.l. (with the European dryopithecines being the sister taxon to the Asian pongines). Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  19. From apes to humans: locomotion as a key feature for phylogeny.

    PubMed

    Senut, Brigitte

    2002-03-01

    If bipedalism has often been considered to be of a crucial interest for understanding hominid evolution, the acceptance of locomotor features to build phylogenies is still far from being a reality in the field. Especially for hominid evolution, it still seems to be difficult to accept that traits, other than craniodental ones, can be useful for defining the major dichotomies. The recent discovery of Australopithecus anamensis suggests a challenging view of the major dichotomy between apes and humans. Whilst it is widely accepted that Ardipithecus ramidus is ancestral to Australopithecus anamensis, which in its turn is ancestral to Australopithecus afarensis and then to later hominids, the postcranial adaptations, which should be taken into account, suggest another branching pattern. Based on the fact that by 4.0 million years two different locomotor patterns can be identified in hominids, two lineages would appear to be present: the "Australopithecine" lineage (with Australopithecus afarensis or Ardipithecus ramidus if the latter is really a hominid sensu stricto) and the "Hominine" lineage (with Australopithecus anamensis = Praeanthropus africanus).

  20. Watering holes: The use of arboreal sources of drinking water by Old World monkeys and apes.

    PubMed

    Sharma, Narayan; Huffman, Michael A; Gupta, Shreejata; Nautiyal, Himani; Mendonça, Renata; Morino, Luca; Sinha, Anindya

    2016-08-01

    Water is one of the most important components of an animal's diet, as it is essential for life. Primates, as do most animals, procure water directly from standing or free-flowing sources such as pools, ponds and rivers, or indirectly by the ingestion of certain plant parts. The latter is frequently described as the main source of water for predominantly arboreal species. However, in addition to these, many species are known to drink water accumulated in tree-holes. This has been commonly observed in several arboreal New World primate species, but rarely reported systematically from Old World primates. Here, we report observations of this behaviour from eight great ape and Old World monkey species, namely chimpanzee, orangutan, siamang, western hoolock gibbon, northern pig-tailed macaque, bonnet macaque, rhesus macaque and the central Himalayan langur. We hypothesise three possible reasons why these primates drink water from tree-holes: (1) coping with seasonal or habitat-specific water shortages, (2) predator/human conflict avoidance, and (3) potential medicinal benefits. We also suggest some alternative hypotheses that should be tested in future studies. This behaviour is likely to be more prevalent than currently thought, and may have significant, previously unknown, influences on primate survival and health, warranting further detailed studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Extreme selective sweeps independently targeted the X chromosomes of the great apes.

    PubMed

    Nam, Kiwoong; Munch, Kasper; Hobolth, Asger; Dutheil, Julien Yann; Veeramah, Krishna R; Woerner, August E; Hammer, Michael F; Mailund, Thomas; Schierup, Mikkel Heide

    2015-05-19

    The unique inheritance pattern of the X chromosome exposes it to natural selection in a way that is different from that of the autosomes, potentially resulting in accelerated evolution. We perform a comparative analysis of X chromosome polymorphism in 10 great ape species, including humans. In most species, we identify striking megabase-wide regions, where nucleotide diversity is less than 20% of the chromosomal average. Such regions are found exclusively on the X chromosome. The regions overlap partially among species, suggesting that the underlying targets are partly shared among species. The regions have higher proportions of singleton SNPs, higher levels of population differentiation, and a higher nonsynonymous-to-synonymous substitution ratio than the rest of the X chromosome. We show that the extent to which diversity is reduced is incompatible with direct selection or the action of background selection and soft selective sweeps alone, and therefore, we suggest that very strong selective sweeps have independently targeted these specific regions in several species. The only genomic feature that we can identify as strongly associated with loss of diversity is the location of testis-expressed ampliconic genes, which also have reduced diversity around them. We hypothesize that these genes may be responsible for selective sweeps in the form of meiotic drive caused by an intragenomic conflict in male meiosis.

  2. Genetic Load of Loss-of-Function Polymorphic Variants in Great Apes.

    PubMed

    de Valles-Ibáñez, Guillem; Hernandez-Rodriguez, Jessica; Prado-Martinez, Javier; Luisi, Pierre; Marquès-Bonet, Tomàs; Casals, Ferran

    2016-03-26

    Loss of function (LoF) genetic variants are predicted to disrupt gene function, and are therefore expected to substantially reduce individual's viability. Knowing the genetic burden of LoF variants in endangered species is of interest for a better understanding of the effects of declining population sizes on species viability. In this study, we have estimated the number of LoF polymorphic variants in six great ape populations, based on whole-genome sequencing data in 79 individuals. Our results show that although the number of functional variants per individual is conditioned by the effective population size, the number of variants with a drastic phenotypic effect is very similar across species. We hypothesize that for those variants with high selection coefficients, differences in effective population size are not important enough to affect the efficiency of natural selection to remove them. We also describe that mostly CpG LoF mutations are shared across species, and an accumulation of LoF variants at olfactory receptor genes in agreement with its pseudogenization in humans and other primate species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. Tandem repeat variation in human and great ape populations and its impact on gene expression divergence

    PubMed Central

    Bilgin Sonay, Tugce; Carvalho, Tiago; Robinson, Mark D.; Greminger, Maja P.; Krützen, Michael; Comas, David; Highnam, Gareth; Mittelman, David; Sharp, Andrew; Marques-Bonet, Tomàs; Wagner, Andreas

    2015-01-01

    Tandem repeats (TRs) are stretches of DNA that are highly variable in length and mutate rapidly. They are thus an important source of genetic variation. This variation is highly informative for population and conservation genetics. It has also been associated with several pathological conditions and with gene expression regulation. However, genome-wide surveys of TR variation in humans and closely related species have been scarce due to technical difficulties derived from short-read technology. Here we explored the genome-wide diversity of TRs in a panel of 83 human and nonhuman great ape genomes, in a total of six different species, and studied their impact on gene expression evolution. We found that population diversity patterns can be efficiently captured with short TRs (repeat unit length, 1–5 bp). We examined the potential evolutionary role of TRs in gene expression differences between humans and primates by using 30,275 larger TRs (repeat unit length, 2–50 bp). Genes that contained TRs in the promoters, in their 3′ untranslated region, in introns, and in exons had higher expression divergence than genes without repeats in the regions. Polymorphic small repeats (1–5 bp) had also higher expression divergence compared with genes with fixed or no TRs in the gene promoters. Our findings highlight the potential contribution of TRs to human evolution through gene regulation. PMID:26290536

  4. Purification and characterization of aminopeptidase (pumAPE) from Ustilago maydis.

    PubMed

    Mercado-Flores, Yuridia; Noriega-Reyes, Yamilet; Ramírez-Zavala, Bernardo; Hernández-Rodríguez, César; Villa-Tanaca, Lourdes

    2004-05-15

    The aminopeptidase pumAPE was purified from the haploid fungus Ustilago maydis FB1 strain. The purification procedure consisted of ammonium sulfate fractionation and three chromatographic steps, which included anion-exchange, hydrophobic interaction, and gel filtration chromatography, resulting in a 23% recovery. The molecular mass of the dimeric enzyme was estimated to be 110 kDa and 58 kDa by gel filtration chromatography and SDS-PAGE, respectively. Enzymatic activity was optimal at pH 7.0 and at 35 degrees C toward Lys-pNA and the pI was determined to be 5.1. The enzyme was inhibited by EDTA-Na2, 1,10- phenanthroline, bestantin, PMSF and several divalent cations (Cu2+, Hg2+ and Zn2+). The aminopeptidase showed a preference for lysine and arginine in the N-position. The K(m) value was 54.4 microM and the Vmax value was 408 micromolmin(-1)mg(-1) for Lys-pNA.

  5. Fungal phosphate transporter serves as a receptor backbone for gibbon ape leukemia virus.

    PubMed

    Pedersen, L; van Zeijl, M; Johann, S V; O'Hara, B

    1997-10-01

    Pit1, the receptor for gibbon ape leukemia virus (GALV), is proposed to be an integral membrane protein with five extracellular loops. Chimeras made between Pit1 homologs differing in permissivity for infection and between Pit1 and the related protein Pit2 have shown that the fourth extracellular loop plays a critical role in infection. However, further elucidation of the roles of the extracellular loops in infection is hampered by the high level of sequence similarity among these proteins. The sodium-dependent phosphate transporter, Pho-4, from the filamentous fungus Neurospora crassa is distantly related to Pit1 and -2, showing an amino acid identity of only 35% to Pit1 in the putative extracellular loops. We show here that Pho-4 itself does not function as a receptor for GALV. Introduction of 12 Pit1-specific amino acid residues in the putative fourth extracellular loop of Pho-4 resulted in a functional GALV receptor. Therefore, the presence of a Pit1 loop 4-specific sequence is sufficient to confer receptor function for the mammalian retrovirus GALV on the fungal phosphate transporter Pho-4.

  6. Artefacts of apes, humans, and others: towards comparative assessment and analysis.

    PubMed

    Gowlett, J A J

    2009-10-01

    This paper explores issues of technology and artefacts in a comparative cross-species frame, using archaeological examples and modern data sets to illustrate points about process and content. It develops the argument that regardless of species, artefacts have a special significance as external projections of the mind, often necessitating cognitive judgements on the basis of several variables and subject to influences by cultural tradition, functional needs, and raw materials. In humans, apes, and other tool using animals, behaviour overlaps in some respects and is vastly different in others. Overlapping aspects are worth seeking out and exploiting, as they provide opportunities to investigate factors influencing variation and to gain insights into cognition. Recent primatological research establishes much more foundation for continuity, but many of the details of artefacts and their variation remain to be explored. This paper presents case studies of variability and standardisation that suggest the limits on variation are as tight in some chimpanzee produced artefacts as in many produced by humans, and functional constraints appear to operate more strongly on some parts of artefacts than others. Thus, degree of standardisation cannot be used as a simple index to 'refinement,' but the widespread overlap in standardisation between human and nonhuman artefacts greatly expands the scope for study.

  7. Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor.

    PubMed

    Kivell, Tracy L; Schmitt, Daniel

    2009-08-25

    Despite decades of debate, it remains unclear whether human bipedalism evolved from a terrestrial knuckle-walking ancestor or from a more generalized, arboreal ape ancestor. Proponents of the knuckle-walking hypothesis focused on the wrist and hand to find morphological evidence of this behavior in the human fossil record. These studies, however, have not examined variation or development of purported knuckle-walking features in apes or other primates, data that are critical to resolution of this long-standing debate. Here we present novel data on the frequency and development of putative knuckle-walking features of the wrist in apes and monkeys. We use these data to test the hypothesis that all knuckle-walking apes share similar anatomical features and that these features can be used to reliably infer locomotor behavior in our extinct ancestors. Contrary to previous expectations, features long-assumed to indicate knuckle-walking behavior are not found in all African apes, show different developmental patterns across species, and are found in nonknuckle-walking primates as well. However, variation among African ape wrist morphology can be clearly explained if we accept the likely independent evolution of 2 fundamentally different biomechanical modes of knuckle-walking: an extended wrist posture in an arboreal environment (Pan) versus a neutral, columnar hand posture in a terrestrial environment (Gorilla). The presence of purported knuckle-walking features in the hominin wrist can thus be viewed as evidence of arboreality, not terrestriality, and provide evidence that human bipedalism evolved from a more arboreal ancestor occupying the ecological niche common to all living apes.

  8. Apes (Gorilla gorilla, Pan paniscus, P. troglodytes, Pongo abelii) versus corvids (Corvus corax, C. corone) in a support task: the effect of pattern and functionality.

    PubMed

    Albiach-Serrano, Anna; Bugnyar, Thomas; Call, Josep

    2012-11-01

    Apes (Gorilla gorilla, Pan paniscus, P. troglodytes, Pong abelii) and corvids (Corvus corax, C. corone) are among the most proficient and flexible tool users in the animal kingdom. Although it has been proposed that this is the result of convergent evolution, little is known about whether this is limited to behavior or also includes the underlying cognitive mechanisms. We compared several species of apes (bonobos, chimpanzees, gorillas, and orangutans) and corvids (carrion crows and common ravens) using exactly the same paradigm: a support task with elements from the classical patterned-string tasks. Corvids proved able to solve at least an easy pattern, whereas apes outperformed corvids with respect to the complexity of the patterns solved, the relative number of subjects solving each problem, and the speed to reach criterion. We addressed the question of whether subjects based their choices purely on perceptual cues or on a more abstract understanding of the problem. This was done by using a perceptually very similar but causally different condition where instead of paper strips there were strip shapes painted on a platform. Corvids' performance did not differ between conditions, whereas apes were able to solve the real but not the painted task. This shows that apes were not basing their choices just on spatial or arbitrary perceptual cues. Instead, and unlike corvids, they must have had some causal knowledge of the task.

  9. Extracellularly secreted APE1/Ref-1 triggers apoptosis in triple-negative breast cancer cells via RAGE binding, which is mediated through acetylation

    PubMed Central

    Lee, Yu Ran; Kim, Ki Mo; Jeon, Byeong Hwa; Choi, Sunga

    2015-01-01

    The present study evaluated the mechanism of apoptosis caused by post-translational modification, hyperacetylation in triple-negative breast cancer (TNBC) cells. We previously showed that trichostatin A (TSA) induced secretion of acetylated apurinic apyrimidinic endonuclease 1/redox factor-1 (Ac-APE1/Ref-1). This is the first report showing that Ac-APE1/Ref-1 initiates apoptosis in TNBC cells by binding to the receptor for advanced glycation end products (RAGE). The functional significance of secreted Ac-APE1/Ref-1 was studied by induction of intracellular hyperacetylation through co-treatment with acetylsalicylic acid and TSA in MDA-MB-231 cells. In response to hyperacetylation, secretion of Ac-APE1/Ref-1 in vesicles was observed, resulting in significantly decreased cell viability and induction of apoptosis with increased expression of RAGE. The hyperacetylation-induced apoptosis was similar in two other TNBC cell lines: BT-459 and MDA-MB-468. Therefore, hyperacetylation may be a therapeutic target for treatment of TNBCs. This study introduces a novel paradigm whereby post-translational modification induces apoptotic cell death in breast cancer cells resistant to standard chemotherapeutic agents through secretion of auto- or paracrine molecules such as Ac-APE1/Ref-1. PMID:26125438

  10. Aminated polyethersulfone-silver nanoparticles (AgNPs-APES) composite membranes with controlled silver ion release for antibacterial and water treatment applications.

    PubMed

    Haider, M Salman; Shao, Godlisten N; Imran, S M; Park, Sung Soo; Abbas, Nadir; Tahir, M Suleman; Hussain, Manwar; Bae, Wookeun; Kim, Hee Taik

    2016-05-01

    The present study reports the antibacterial disinfection properties of a series of silver nanoparticle (AgNP) immobilized membranes. Initially, polyethersulfone (PES) was functionalized through the introduction of amino groups to form aminated polyethersulfone (NH2-PES, APES). AgNPs were then coordinately immobilized on the surface of the APES composite membrane to form AgNPs-APES. The properties of the obtained membrane were examined by FT-IR, XPS, XRD, TGA, ICP-OES and SEM-EDAX analyses. These structural characterizations revealed that AgNPs ranging from 5 to 40 nm were immobilized on the surface of the polymer membrane. Antibacterial tests of the samples showed that the AgNPs-APES exhibited higher activity than the AgNPs-PES un-functionalized membrane. Generally, the AgNPs-APES 1 cm × 3 cm strip revealed a four times longer life than the un-functionalized AgNPs polymer membranes. The evaluation of the Ag(+) leaching properties of the obtained samples indicated that approximately 30% of the AgNPs could be retained, even after 12 days of operation. Further analysis indicated that silver ion release can be sustained for approximately 25 days. The present study provides a systematic and novel approach to synthesize water treatment membranes with controlled and improved silver (Ag(+)) release to enhance the lifetime of the membranes.

  11. APE1 overexpression in XRCC1-deficient cells complements the defective repair of oxidative single strand breaks but increases genomic instability

    PubMed Central

    Sossou, Marguerite; Flohr-Beckhaus, Claudia; Schulz, Ina; Daboussi, Fayza; Epe, Bernd; Radicella, J. Pablo

    2005-01-01

    XRCC1 protein is essential for mammalian viability and is required for the efficient repair of single strand breaks (SSBs) and damaged bases in DNA. XRCC1-deficient cells are genetically unstable and sensitive to DNA damaging agents. XRCC1 has no known enzymatic activity and is thought to act as a scaffold protein for both SSB and base excision repair activities. To further define the defects leading to genetic instability in XRCC1-deficient cells, we overexpressed the AP endonuclease APE1, shown previously to interact with and be stimulated by XRCC1. Here, we report that the overexpression of APE1 can compensate for the impaired capability of XRCC1-deficient cells to repair SSBs induced by oxidative DNA damage, both in vivo and in whole-cell extracts. We show that, for this kind of damage, the repair of blocked DNA ends is rate limiting and can be performed by APE1. Conversely, APE1 overproduction resulted in a 3-fold increase in the sensitivity of XRCC1-deficient cells to an alkylating agent, most probably due to the accumulation of SSBs. Finally, the overproduction of APE1 results in increases of 40% in the frequency of micronuclei and 33% in sister chromatid exchanges of XRCC1− cells. These data suggest that the spontaneous generation of AP sites could be at the origin of the SSBs responsible for the spontaneous genetic instability characteristic of XRCC1-deficient cells. PMID:15647512

  12. Frequent and recent human acquisition of simian foamy viruses through apes' bites in central Africa.

    PubMed

    Betsem, Edouard; Rua, Réjane; Tortevoye, Patricia; Froment, Alain; Gessain, Antoine

    2011-10-01

    Human infection by simian foamy viruses (SFV) can be acquired by persons occupationally exposed to non-human primates (NHP) or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (pro)viral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men) and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436) or Bantus (1085) live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR) were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2%) persons were found to be infected. In the second group, 37/198 (18.6%) persons were SFV positive. They were mostly infected by apes (37/39) FV (mainly gorilla). Infection by monkey FV was less frequent (2/39). The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83%) are aged 20 to 40 years and acquired the infection during the last twenty years. The (pro)viral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 10(5) cells) in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question.

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

    PubMed

    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

  14. Response facilitation in the four great apes: is there a role for empathy?

    PubMed

    Amici, Federica; Aureli, Filippo; Call, Josep

    2014-01-01

    Contagious yawning is a form of response facilitation found in humans and other primates in which observing a model yawning enhances the chance that the observer will also yawn. Because contagious yawning seems to be more easily triggered when models are conspecifics or have a strong social bond with the observer, it has been proposed that contagious yawning is linked to empathy. A possible way to test this hypothesis is to analyze whether individuals' responses differ when they observe models yawning or performing different involuntary (i.e., nose wiping, scratching) and voluntary (i.e., hand closing, wrist shaking) actions that are not linked to empathy. In this study, we tested the four great ape species with two different setups by exposing them to a human experimenter repeatedly performing these actions online, and video-recorded conspecifics repeatedly performing these actions on a screen. We examined which behaviors were subject to response facilitation, whether response facilitation was triggered by both human models and video-recorded conspecifics, and whether all species showed evidence of response facilitation. Our results showed that chimpanzees yawned significantly more when and shortly after watching videos of conspecifics (but not humans) yawning than in control conditions, and they did not do so as a response to increased levels of anxiety. For all other behaviors, no species produced more target actions when being exposed to either model than under control conditions. Moreover, the individuals that were more "reactive" when watching yawning videos were not more reactive when exposed to other actions. Since, at least in chimpanzees, (1) subjects only showed response facilitation when they were exposed to yawning and (2) only if models were conspecifics, it appears that contagious yawning is triggered by unique mechanisms and might be linked to empathy.

  15. Frequent and Recent Human Acquisition of Simian Foamy Viruses Through Apes' Bites in Central Africa

    PubMed Central

    Betsem, Edouard; Rua, Réjane; Tortevoye, Patricia; Froment, Alain; Gessain, Antoine

    2011-01-01

    Human infection by simian foamy viruses (SFV) can be acquired by persons occupationally exposed to non-human primates (NHP) or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (pro)viral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men) and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436) or Bantus (1085) live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR) were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2%) persons were found to be infected. In the second group, 37/198 (18.6%) persons were SFV positive. They were mostly infected by apes (37/39) FV (mainly gorilla). Infection by monkey FV was less frequent (2/39). The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83%) are aged 20 to 40 years and acquired the infection during the last twenty years. The (pro)viral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 105 cells) in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question. PMID:22046126

  16. The interpretive power of infraorbital foramen area in making dietary inferences in extant apes.

    PubMed

    Muchlinski, Magdalena N; Deane, Andrew S

    2014-08-01

    The infraorbital foramen (IOF) is located below the orbit and transmits the sensory infraorbital nerve (ION) to mechanoreceptors located throughout the maxillary region. The size of the IOF correlates with the size of the ION; thus, the IOF appears to indicate relative touch sensitivity of maxillary region. In primates, IOF size correlates well with diet. Frugivores have relatively larger IOFs than folivores or insectivores because fruit handling/processing requires increased touch sensitivity. However, it is unknown if the IOF can be used to detect subtle dietary differences among closely related hominoid species. Hominoids are traditionally grouped into broad dietary categories, despite the fact that hominoid diets are remarkably diverse. This study examines whether relative IOF size is capable of differentiating among the dietary preferences of closely related species with overlapping, yet divergent diets. We measured IOF area in Hylobates lar, Symphalangus syndactulus, Pongo pygmaeus spp., Pan troglodytes, Gorilla gorilla, Gorilla beringei graueri, and Gorilla beringei beringei. We classified each species as a dedicated folivore, mixed folivore/frugivore, soft object frugivore, or hard object frugivore. The IOF is documented to be larger in more frugivorous species and smaller in more folivorous taxa. Interestingly, G.b. beringei, had the largest relative IOF of any gorilla, despite being a dedicated folivore. G.b. beringei does have unique food processing behavior that relies heavily on maxillary mechanoreception, thus this finding is not entirely unsupported behaviorally. The results of this study provide evidence that the IOF is an informative feature in interpretations of fossil apes. Copyright © 2014 Wiley Periodicals, Inc.

  17. Relative placement of the mandibular fossa in great apes and humans.

    PubMed

    Sherwood, Richard J; Rowley, Rebecca B; Ward, Steven C

    2002-07-01

    Several researchers have investigated, or commented on, the relative placement of the hominin mandibular fossa with regard to brain expansion and masticatory function. Two confounding factors are identified in this previous work. First, a number of different measurement techniques have been applied, confusing comparisons between studies. Second, the effects of squamous thickening due to temporal bone pneumatization are shown to influence measurements based relative to the ectocranial margin of the skull. To investigate the influence of these factors, a sample of adult human (n=12), chimpanzee (n=12), gorilla (n=15), and orang-utan (n=8) skulls from the Cleveland Museum of Natural History, University of Wisconsin Zoology Museum, and University of Wisconsin Anthropology collections, were CT scanned. Coronal scans were horizontally aligned and measured on a personal computer using ImageJ (NIH). To identify fossa placement, fossa breadth was measured as the projected distance in the coronal plane between the tip of the entoglenoid to lateral margin of the articular surface. A second distance, from the tip of the entoglenoid to a sagittal plane, tangent to the lateralmost margin of the endocranial surface was taken to indicate the extent of medial placement of the fossa. By eliminating the influence of pneumatization, these data unambiguously confirmed the medial placement of the human fossa and show all great apes as having a laterally placed fossa. Similar measurements on three fossil hominins, KNM-BC 1 (Homo sp. indet.), OH 5 and KNM-ER 23000 (Paranthropus boisei) demonstrate that, while all specimens demonstrate a broad fossa, only KNM-BC 1 is characterized by a relatively medial placement while the latter two display lateral placement.

  18. Serological evidence for variation in the incidence of herpesvirus infections in different species of apes.

    PubMed Central

    Eberle, R; Hilliard, J K

    1989-01-01

    Sera from captive lowland gorillas, chimpanzees, orangutans, and gibbons were screened by enzyme-linked immunosorbent assay (ELISA) for antibody to herpesviruses serologically related to human herpes simplex virus types 1 and 2 (HSV-1, HSV-2), a baboon virus (SA8), and a macaque herpesvirus (B virus). The incidence of herpesvirus antibodies varied considerably among the different species, gorillas having the highest incidence of seropositivity (65.4%) and orangutans the lowest. The virus specificity of positive sera was further analyzed by examining the kinetics of virus neutralization, competition of reactivity in ELISAs, and immunoblotting against HSV-1, HSV-2, SA8, and B virus antigens. Using these assays, the majority of positive gorilla sera (49 of 53, 92%) were determined to react in a manner identical to human HSV-1 immune sera. The remaining four positive gorilla sera reacted as HSV-2-positive sera. In contrast, the majority of positive chimpanzee sera (5 of 7, 71%) reacted as HSV-2 immune rather than HSV-1 immune. All positive sera from gibbon apes reacted as HSV-1 positive. No orangutan sera were identified which gave positive reactions by ELISAs to any of the four primate herpesviruses tested. Although four orangutan sera gave equivocal results against HSV-1 antigen, further analysis by immunoblotting could not confirm any specific reactivity with any of the primate herpesvirus antigens. Varied reactivity among individual animals with both SA8 and B virus proteins was observed, but none of the seropositive primates detected appeared to be infected with either of these simian viruses. Three gorilla sera had antigen recognition patterns slightly different from those of HSV-2-positive human and chimpanzee sera and another HSV-2-positive gorilla serum, raising the possibility that these animals harbor an indigenous virus related to HSV-2. Images PMID:2546978

  19. Sequences in gibbon ape leukemia virus envelope that confer sensitivity to HIV-1 accessory protein Vpu.

    PubMed

    Janaka, Sanath Kumar; Lucas, Tiffany M; Johnson, Marc C

    2011-11-01

    HIV-1 efficiently forms pseudotyped particles with many gammaretrovirus glycoproteins, such as Friend murine leukemia virus (F-MLV) Env, but not with the related gibbon ape leukemia virus (GaLV) Env or with a chimeric F-MLV Env with a GaLV cytoplasmic tail domain (CTD). This incompatibility is modulated by the HIV-1 accessory protein Vpu. Because the GaLV Env CTD does not resemble tetherin or CD4, the well-studied targets of Vpu, we sought to characterize the modular sequence in the GaLV Env CTD required for this restriction in the presence of Vpu. Using a systematic mutagenesis scan, we determined that the motif that makes GaLV Env sensitive to Vpu is INxxIxxVKxxVxRxK. This region in the CTD of GaLV Env is predicted to form a helix. Mutations in the CTD that would break this helix abolish sensitivity to Vpu. Although many of these positions can be replaced with amino acids with similar biophysical properties without disrupting the Vpu sensitivity, the final lysine residue is required. This Vpu sensitivity sequence appears to be modular, as the unrelated Rous sarcoma virus (RSV) Env can be made Vpu sensitive by replacing its CTD with the GaLV Env CTD. In addition, F-MLV Env can be made Vpu sensitive by mutating two amino acids in its cytoplasmic tail to make it resemble more closely the Vpu sensitivity motif. Surprisingly, the core components of this Vpu sensitivity sequence are also present in the host surface protein CD4, which is also targeted by Vpu through its CTD.

  20. Pseudotyping incompatibility between HIV-1 and gibbon ape leukemia virus Env is modulated by Vpu.

    PubMed

    Lucas, Tiffany M; Lyddon, Terri D; Cannon, Paula M; Johnson, Marc C

    2010-03-01

    The Env protein from gibbon ape leukemia virus (GaLV) has been shown to be incompatible with human immunodeficiency virus type 1 (HIV-1) in the production of infectious pseudotyped particles. This incompatibility has been mapped to the C-terminal cytoplasmic tail of GaLV Env. Surprisingly, we found that the HIV-1 accessory protein Vpu modulates this incompatibility. The infectivity of HIV-1 pseudotyped with murine leukemia virus (MLV) Env was not affected by Vpu. However, the infectivity of HIV-1 pseudotyped with an MLV Env with the cytoplasmic tail from GaLV Env (MLV/GaLV Env) was restricted 50- to 100-fold by Vpu. A Vpu mutant containing a scrambled membrane-spanning domain, Vpu(RD), was still able to restrict MLV/GaLV Env, but mutation of the serine residues at positions 52 and 56 completely alleviated the restriction. Loss of infectivity appeared to be caused by reduced MLV/GaLV Env incorporation into viral particles. The mechanism of this downmodulation appears to be distinct from Vpu-mediated CD4 downmodulation because Vpu-expressing cells that failed to produce infectious HIV-1 particles nonetheless continued to display robust surface MLV/GaLV Env expression. In addition, if MLV and HIV-1 were simultaneously introduced into the same cells, only the HIV-1 particle infectivity was restricted by Vpu. Collectively, these data suggest that Vpu modulates the cellular distribution of MLV/GaLV Env, preventing its recruitment to HIV-1 budding sites.

  1. The relationships among jaw-muscle fiber architecture, jaw morphology, and feeding behavior in extant apes and modern humans.

    PubMed

    Taylor, Andrea B; Vinyard, Christopher J

    2013-05-01

    The jaw-closing muscles are responsible for generating many of the forces and movements associated with feeding. Muscle physiologic cross-sectional area (PCSA) and fiber length are two architectural parameters that heavily influence muscle function. While there have been numerous comparative studies of hominoid and hominin craniodental and mandibular morphology, little is known about hominoid jaw-muscle fiber architecture. We present novel data on masseter and temporalis internal muscle architecture for small- and large-bodied hominoids. Hominoid scaling patterns are evaluated and compared with representative New- (Cebus) and Old-World (Macaca) monkeys. Variation in hominoid jaw-muscle fiber architecture is related to both absolute size and allometry. PCSAs scale close to isometry relative to jaw length in anthropoids, but likely with positive allometry in hominoids. Thus, large-bodied apes may be capable of generating both absolutely and relatively greater muscle forces compared with smaller-bodied apes and monkeys. Compared with extant apes, modern humans exhibit a reduction in masseter PCSA relative to condyle-M1 length but retain relatively long fibers, suggesting humans may have sacrificed relative masseter muscle force during chewing without appreciably altering muscle excursion/contraction velocity. Lastly, craniometric estimates of PCSAs underestimate hominoid masseter and temporalis PCSAs by more than 50% in gorillas, and overestimate masseter PCSA by as much as 30% in humans. These findings underscore the difficulty of accurately estimating jaw-muscle fiber architecture from craniometric measures and suggest models of fossil hominin and hominoid bite forces will be improved by incorporating architectural data in estimating jaw-muscle forces. Copyright © 2013 Wiley Periodicals, Inc.

  2. Construction of a Full-Atomic Mechanistic Model of Human Apurinic/Apyrimidinic Endonuclease APE1 for Virtual Screening of Novel Inhibitors.