Between the years of 1991 and 1995, two different chimpanzee nursery rearing strategies were employed by caregivers and research staff at the Yerkes National Primate Research Center. One of these strategies included, in addition to the basic care provided by both nurseries, an additional 4 hours of human contact for 5 days each week. This human contact was provided by caregivers instructed in the behavior of chimpanzee mothers toward their offspring and instructed to emulate that behavior as much as possible. Various measures of cognitive and motor development were taken during the first year of the nursery-reared chimpanzees' lives; additionally, a modified version of the Strange Situation Test, used to measure attachment, was used to assess the chimpanzees' attachment style to their primary human caregiver. Based on these measures, chimpanzees reared in the standard care nursery (without the additional human contact) were significantly more likely to exhibit disorganized attachment styles towards their human caregiver; additionally, the standard care chimpanzees displayed less advanced motor and cognitive development. The responsive care chimpanzees (reared with the additional human contact) developed cognitively and in terms of motor function at a faster rate than the standard care chimpanzees; they also exhibited less coping skills. After one year of rearing in these two nurseries, all the chimpanzees were reared in conspecific social groups and the differential nurseries were terminated. In 2011-2012, 22 out of 49 of the original chimpanzee subjects were reassessed in an attempt to determine of long term effects of these differential rearing styles could still be detected. Chimpanzees that were identified as exhibiting disorganized attachment at one year of age exhibited significantly higher rates of abnormal behavior as compared to those that did not exhibit a disorganized attachment style at one year of age. Chimpanzees reared in both nurseries exhibited significantly higher rates of abnormal behavior, solicitation of, and attendance to humans as compared to chimpanzees that were mother-reared. Additionally, chimpanzees reared in either nursery were rated by survey respondents as exhibiting significantly higher human orientation and significantly lower subjective well-being as compared to mother-reared chimpanzees. Finally, trends found in the data consistently indicated that chimpanzees reared with more extensive human contact (responsive care) exhibited higher rates of abnormal behavior, solicitation of, and attendance toward humans as compared to standard care chimpanzees. Trends also indicated consistently that responsive care subjects were scored higher on human orientation and lower on subjective well-being by survey respondents. Sign tests were conducted to explore these differences and consistent support was found for these trends as significant. Further research should be conducted to explore welfare-related issues as related to differential nursery rearing strategies for chimpanzees.

Les processus de l'évolution des génomes, particulièrement des génomes de primates, font l'objet de cette thèse. Ont été ainsi creusées les questions de la conservation ou non de séquences nucléiques de précurseurs peptidiques dans la lignée des primates, et de la mise en place, de l'évolution et de l'expression de deux familles de gènes spécifiques des primates. <br /><br />Brassages d'exons, rétrotransposition, duplications... sont impliqués dans la création de nouveaux gènes. L'étude de la création et des premiers temps d'un gène nécessite la mise en évidence de gènes récents, ayant conservé les caractéristiques de leur mise en place. <br /> Deux familles de gènes ont retenu mon attention:<br />1. Les gènes PMCHL ont été créés récemment par des processus de rétroposition, remaniements, insertions/délétions et accumulation de mutations. Des analyses de structure et phylogénétique permettent une meilleure compréhension de l'origine de ces gènes spécifiques des Primates. Les gènes PMCHL sont transcrits, de façon tissu-spécifique, et présentent de nombreux épissages alternatifs. Enfin, l'expression des ARN messagers PMCHL est comparée dans le cerveau de l'Homme et du Macaque. <br />2. Les gènes dérivés de GUSB ont été identifies par hybridation in situ fluorescente chez les Primates. Une recherche systématique dans le génome humain a permis la découverte et la caractérisation d'une grande famille de gènes comptant plus de quinze paralogues chez l'Homme. L'analyse structurale et phylogénétique de ces séquences a permis de préciser l'histoire de leur mise en place et de leur évolution. Certains des membres de cette famille de gènes ont en outre acquis une capacité transcriptionnelle.

Parmi les approches qui visent à déterminer la façon dont les organismes se diversifient dans le temps et dans l'espace, la biogéographie tente de reconstruire l'histoire des peuplements à partir des distributions des taxons, tandis que la phylogéographie analyse l'évolution d'une lignée à la fois. Dans cette étude, nous nous sommes proposés de tester les hypothèses biogéographiques formulées pour la faune tropicale (théorie des refuges, des barrières fluviales, des gradients environnementaux...), en appliquant l'approche moléculaire à quelques taxons de Mammifères africains (Insectivores, Rongeurs, Primates). Nous avons cherché à déterminer l'apport et les limites de la technique moléculaire la plus couramment employée en biologie évolutive : le séquençage d'ADN mitochondrial. <br />Nous avons d'abord tenté d'obtenir une phylogénie moléculaire de quelques taxons potentiellement intéressants pour la biogéographie, dans le but de vérifier leur monophylie et de calibrer une horloge moléculaire. Puis, nous avons recherché et comparé les schémas phylogéographiques de quatre espèces de petits mammifères forestiers et d'une super-espèce de primates. Enfin, nous nous sommes intéressés aux processus évolutifs impliqués dans la spéciation. Nous avons évalué le mode géographique de spéciation et l'évolution de quelques traits d'histoire de vie chez les primates de la tribu des Cercopithecini. <br />Nos résultats phylogénétiques confirment que l'histoire des gènes n'est pas forcément celle des taxons et qu'il est important de prendre en compte plusieurs sources d'information indépendantes, telles que des gènes non liés sur la même molécule, la morphologie, l'écologie, et le comportement. L'étude des modalités de la spéciation, qui est tributaire de la fiabilité des analyses phylogénétiques, indique une prédominance de l'allopatrie et des événements de vicariance du Miocène et du Pliocène chez les Cercopithecini. Enfin, les analyses phylogéographiques ont révélé quatre scénarios phylogéographiques différents pour les quatre modèles retenus, ce qui peut refléter soit des distributions initiales différentes, soit une réponse différentielle aux mêmes événements selon les taxons. Ces scénarios présentent une certaine concordance avec les régions fauniques définies pour les forêts d'Afrique centrale, mais suggèrent que les événements de divergence intra-spécifique remonteraient au Plio-Pleistocène et seraient donc beaucoup plus anciens que les derniers épisodes de fragmentation de la forêt liés aux cycles glaciaires.

Die vorliegende Arbeit soll dazu beitragen, Unstimmigkeiten in den Verwandtschaftsverhältnissen innerhalb der Papionini, einem Stamm innerhalb der Altweltaffen (Cercopithecidae), zu klären. Die Papionini, die zusammen mit den Cercopithecini die Unterfamilie der Cercopithecinae bilden, beinhalten sieben Gattungen (Macaca, Cercocebus, Mandrillus, Lophocebus, Papio, Theropithecus, Rungwecebus) und 45 Arten. Sechs der sieben Gattungen kommen heute hauptsächlich in Afrika vor. Eine Ausnahme ist die Gattung Papio, die mit einer Art (P. hamadryas) auch in Südwest-Arabien vorkommt. Im Gegensatz zu den sechs hauptsächlich afrikanischen Gattungen hat die siebte Gattung (Macaca) nur ein kleines Verbreitungsgebiet im Norden Afrikas und kommt sonst hauptsächlich in Asien vor. Fossilfunde belegen allerdings, dass während des Plio- und Pleistozäns die Gattungen Macaca und Theropithecus auch in Europa vorkamen. Von der Gattung Theropithecus, die heute ausschließlich in Afrika beheimatet ist, wurden zudem auch Fossilien aus dem Pliozän im Norden Indiens gefunden. Die Verwandtschaftsbeziehungen innerhalb der Papionini wurden bisher mit Hilfe morphologischer und genetischer Merkmale untersucht, allerdings waren die Ergebnisse nicht immer übereinstimmend und es gibt immer noch viele Unklarheiten. Zum einen ist nicht eindeutig geklärt, wie die Gattungen Papio, Lophocebus und Theropithecus zu einander in Beziehung stehen. Zum anderen ist auch unklar, wie die einzelnen Pavianarten innerhalb der Gattung Papio mit einander verwandt sind. Außerdem sind auch die Verwandtschaftsverhältnisse zwischen und innerhalb der Artgruppen der Makaken nicht eindeutig geklärt. Um mehr Klarheit in die Evolution der Papionini zu bringen, habe ich im Rahmen dieser Arbeit drei Studien durchgeführt (Kapitel 2-4). Ziel dabei war es, Verwandtschaftsbeziehungen auf unterschiedlichen taxonomischen Ebenen (zwischen und innerhalb von Gattungen, sowie innerhalb einer Art) zu untersuchen. Dazu wurden komplette mitochondriale Genome von Vertretern der Papionini sequenziert und damit Phylogenien und Aufspaltungszeiten berechnet. Die Ergebnisse meiner Arbeit zeigen unter anderem drei Hauptkladen innerhalb der Papionini (Kapitel 2): 1) Papio, Theropithecus, Lophocebus; 2) Mandrillus, Cercocebus; 3) Macaca, wobei Macaca in der mitochondrialen Phylogenie näher mit Mandrillus und Cercocebus verwandt zu seien scheint und nicht wie erwartet, als Schwestergruppe der afrikanischen Papionini abgebildet wird; ein Ergebnis, das im Widerspruch zu nukleären und morphologischen Studien steht. Meine Arbeit zeigt auch, dass komplette mitochondriale Genome in manchen Fällen nicht ausreichen, um phylogenetische Beziehungen vollständig zu rekonstruieren. So bleibt weiterhin unklar wie die Gattungen Papio, Theropithecus und Lophocebus zueinander stehen (Kapitel 2). Außerdem zeigen die Ergebnisse Paraphylien für Mandrillus und Cercocebus (Kapitel 2), sowie innerhalb der Paviane (Kapitel 3). Die Paviane werden dabei gemäß ihrer geographischen Verbreitung und nicht nach ihrer taxonomischen Zugehörigkeit abgebildet, wodurch die meisten Pavian-Arten paraphyletisch sind. Der Grund für diese Baumtopologie ist sehr wahrscheinlich sekundärer Genfluss zwischen parapatrisch vorkommenden Pavian-Arten. In der dritten Studie (Kapitel 4), in der innerartliche Verwandtschaftsverhältnisse innerhalb einer südostasiatischen Makaken-Artgruppe (Macaca fascicularis) untersucht wurden, zeigt sich eine klare Unterteilung in eine kontinentale und eine insulare Klade. Sowohl die kontinentale, als auch die insulare Linie sind auf Sumatra zu finden, was für einen sekundären genetischen Austausch zwischen beiden Populationen spricht. Generell kann man sagen, dass komplette mitochondriale Genome robuste Phylogenien mit hoher statistischer Unterstützung ergeben, die eine gute Grundlage für künftige vergleichende Studien bilden. Die berechneten Aufspaltungszeiten stimmen weitestgehend mit vorherigen Studien überein, wobei sich die ermittelten Konfidenzintervalle verkleinert haben. Allerdings zeigt die Arbeit auch, dass Phylogenien basierend auf mitochondrialen Genomen keine hohe Auflösung erzielen wenn sich Taxa innerhalb kurzer Zeit voneinander trennten. Die hier gezeigten Paraphylien und die abweichenden Ergebnisse zu nukleären Studien wurden höchstwahrscheinlich durch sekundären genetischen Austausch hervorgerufen. Um Verwandtschaftsverhältnisse möglichst exakt rekonstruieren zu können, müssen neben der maternal-vererbten, mitochondrialen Linie noch paternal- und biparentalvererbte Merkmale in Betracht gezogen werden. Zu beachten ist in diesem Zusammenhang, dass ein bestimmter molekularer Marker immer nur eine mögliche Phylogenie von vielen wiedergibt.

It is not clear whether genes of the innate immune system of vertebrates are subject to the same selective pressures as genes of the adaptive immune system, despite the fact that innate immunity genes lie directly at the interface between host and pathogens. The lack of consensus about the incidence, type, and strength of selection acting on vertebrate innate immunity genes motivated this study. The goal of this work was to elucidate the general principles of innate immune receptor evolution within and between species. A phylogenetic analysis of the Toll-like receptor 5 (TLR5) in primates showed an excess of nonsynonymous substitutions at certain codons, a pattern that is consistent with recurrent positive selection. The putative sites under selection often displayed radical substitutions, independent parallel changes, and were located in functionally important regions of the protein. In contrast with this interspecific pattern, population genetic analysis of this gene in humans and chimpanzees did not provide conclusive evidence of recent selection. The frequency and distribution of a TLR5 null mutation in human populations further suggested that TLR5 function might be partially redundant in the human immune system (Appendix A). Comparable analyses of the remaining nine human TLRs produced similar results and further pointed to a biologically meaningful difference in the pattern of molecular evolution between TLRs specialized in the recognition of viral nucleic acids and the other TLRs (Appendix B). The general picture that emerges from these studies challenges the conventional idea that pattern recognition receptors are subject to an extreme degree of functional constraint dictated by the recognition of molecules that are essential for microbial fitness. Instead, TLRs display patterns of substitution between species that reflect an old history of positive selection in primates. A common theme, however, is that only a restricted proportion of sites is under positive selection, indicating an equally important role for purifying selection as a conservative force in the evolution of this gene family. A comparative analysis of evolutionary rates at fifteen loci involved in innate, intrinsic and adaptive immunity, and mating systems revealed that more promiscuous species are on average under stronger selection at defense genes (Appendix C). Although the effect is weak, this suggests that sexual promiscuity plays some role in the evolution of immune loci by affecting the risk of contracting infectious diseases.

Ebola virus (EBOV) is a zoonotic pathogen which causes a fulminant hemorrhagic fever and results in up to 90% fatality. Despite efforts over the past 38 years, a licensed prophylactic or post-exposure option remains unavailable. Several experimental vaccines have already demonstrated protection from lethal EBOV disease in nonhuman primates (NHPs). However, attempts to translate this research from bench to bedside have been hampered, since the immune responses that correlate with protection against EBOV are not well-defined. Without this information, it is not possible to reliably predict the efficacy of vaccines or treatments in humans without lethal challenge. The goal of this thesis is to determine the immune parameters that are predictive of protection against EBOV. Due to the rapid speed of EBOV pathogenesis, it was originally hypothesized that a rapid and robust CD8+ T-cell response must be crucial for survival. Using a previously-characterized adenovirus-vectored Ebola vaccine (Ad5-optGP), transgenic/knockout C57BL/6J mice with ablation for selected immune responses were vaccinated and challenged 28 days later. Surprisingly, while CD8+ T-cell knockout mice survived infection, B-cell knockout mice did not, indicating that the antibody response played a critical role in protection. Humoral and cell-mediated responses were compared between survivor and moribund guinea pigs and NHPs from previous vaccination and post-exposure therapy experiments, either with Ad5-optGP or a vesicular stomatitis virus (VSV)-vectored vaccine (VSVΔG/EBOVGP). Circulating EBOV glycoprotein (GP)-specific IgG antibody levels were the best correlation for protection independent of vaccine platform or timing of exposure (p<0.0001), strongly supporting the role of antibody responses in the control of EBOV infection. To demonstrate that antibodies are also responsible for protection, three previously-characterized monoclonal antibodies recognizing different GP epitopes were combined into a cocktail (ZMAb). Initiation of ZMAb treatment 1 and 2 days post infection (dpi) with EBOV protected 100% and 50% of NHPs, respectively. These results provide a reliable measure for predicting protection from EBOV in three commonly used animal models, and present a strong case for the use of antibodies as an effective post-exposure treatment. This knowledge will ultimately help in the development and validation of a clinical product against EBOV infection.

The following research paper was concerned with five basic objectives:(1) outlining the major theoretical and methodological approaches used in the reconstruction of early hominid social behavior/social structure as a context in which to view Richard Wrangham's and Michael Ghiglieri's phylogenetic models of stem-hominid social structure.(2) examining Wrangham's and Ghiglieri's models of stem-hominid and chimpanzee social structure.(3) indicating how theoretical and methodological aspects of structure essentially represent an extension of the theoretical and methodological approaches the same researchers applied to their models of chimpanzee social structure.(4) addressing the theoretical and methodological deficiences of Wrangham's and Ghiglieri's models of chimpanzee social structure.(5) providing suggestions for improved phylogenetic models of early hominid social structure.The first objective was achieved by: (a) reviewing Tooby and Devore's (1986) and Wrangham's (1986) evaluations of the major theoretical approaches and methodologies used in the reconstruction of hominid social behavior/structure (b) defining, classifying and evaluating Wrangham's and Ghiglieri's phylogenetic approaches within this context.The second objective was accomplished by outlining, analyzing, and comparing/contrasting Wrangham's and Ghiglieri's phylogenetic models of stem-hominid social structure (i.e.Wrangham 1986; Ghiglieri 1987, 1989) and Wrangham's and Ghiglieri's models of chimpanzee social structure (i.e. Wrangham 1975, 1979; Ghiglieri 1984, 1985, 1987, 1989).The third objective was achieved by recognizing how Wrangham and Ghiglieri used/stressed principles and concepts derived from evolutionary biology and/or behavioral ecology to develop their models of stem-hominid and chimpanzee social structure. This analysis showed that Wrangham's models of social structure were more favorably inclined toward the method of behavioral ecology than Ghiglieri's models, which favored a sociobiological paradigm. Furthermore, although neither researcher relied exclusively on the above theoretical approaches, the main thrust of their argument often centered around it. For instance, Wrangham's analysis of chimpanzee social structure (Wrangham 1975, 1979) indicated that the ultimate cause of that structure was ecological i.e., patchy food distribution leads to wide female dispersal for optimal foraging efficiency, which in turn favors a male kin breeding group that can maintain a territority that includes several individual female ranges. In contrast, Wrangham's phylogenetic model of the social structure of the stem-hominid (Wrangham, 1986) suggested that phylogenetic inertia may be partially responsible for the shared social features found among African Hominoidea. However, in the same work, Wrangham also suggested that further socioecological analysis of African apes may indicate whether food distribution and its effects on female dispersion/association may partially explain conservative African ape social features.Ghiglieri's phylogenetic model of the stem-hominid (1987, 1989), on the other hand, explained the conservative social features of bonobos, common chimpanzees, and hominids to be primarily a product of phylogenetic inertia and sexual selection. Furthermore, for Ghiglieri the most important sexual selection variable was a male communal reproductive strategy. This, according to Ghiglieri, is the ultimate cause of social structure. Notably, Ghiglieri (1984, 1985) had earlier stressed the overiding importance of a male communal reproductive strategy but was less dogmatic in his insistence that chimpanzees had essentially solved their ecological problems (e.g. that they had solved the food distribution problem by fusion-fission sociality; predators were never a real problem). Nevertheless, Ghiglieri's earlier position similarily expressed the idea that a communal reproductive strategy constituted the ultimate cause of social structure.The fourth objective was accomplished by presentation of an alternative model of chimpanzee social behavior which suggested that structure; the effect of phylogenetic inertia on social structure; chimpanzee social structure is the combined product of ecological and sexual selection forces: female optimal foraging, male mating strategies, and predator pressure. The model was considered by the author to be unique in that it integrated essential aspects of both Wrangham's and Ghiglieri's models and, in addition, provided support for Alexander's (1974) contention that predation pressure is an ultimate cause of ape social structure. The model also outlined scenarios for the evolution of chimpanzee group._ extensibility (fusion-fission sociality) and the capacity for warfare among chimpanzees.The last objective was achieved by a discussion of the implications that the author's model had for phylogenetic models of stem-hominid social structure. In this discussion the author reviewed the following issues as they related to the phylogenetic reconstruction of hominid social structure: the role of phylogeny and/or ecology in the causation of social encountered when using a phylogenetic referential model for the personal biases that enter into phylogenetic econstructions; pitfalls reconstruction of early hominid social evolution; the significance of chimpanzee models of social structure.The importance of the preceding study lay in its ability to stimulate improved conceptual models of African hominoid social structure. / Department of Anthropology

Understanding the evolutionary basis for human-specific phenotypes such as complex speech and language, advanced cognition or the unique preparation of their food is a topic of broad interest. Approaches focusing on comparisons of the genomic DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) sequence between species, individuals or tissues allow for the identification of evolutionary sequence changes, some of these changes may underlie differences in phenotypes. In addition, differences in when, where and how much of a particular gene is present may also contribute to functional changes and therefore also to phenotypic differences. The resources to make such comparisons using genetic data are now available. The genome sequences of a number of outgroups: all living great apes, as well two archaic humans, are now publically available. Studying gene expression on the RNA level - a precursor of the protein expression - is considerably easier and cheaper than the measurement of expression of the protein itself. It has been shown that the RNA and protein expression levels are well correlated and therefore measuring RNA levels provides a good proxy for the expression of the protein. Using high-throughput sequencing techniques, relatively unbiased expression comparison is now possible because the RNA from any species can be sequenced directly, rather than being captured on arrays which are designed based on a particular reference sequence. The aim of this research was to use gene expression as a molecular phenotype to identify changes relevant to human-specific biology and study the difference between humans and their closest living relatives to understand patterns and differences in the gene expression and in gene expression regulation in multiple tissues in primates using high-throughput sequencing techniques. In my thesis, I describe two analyses to address open questions in the field of gene expression and genes expression regulation in humans. In the first part I will analyze how the effect of different diets impact gene expression using a mouse model. Two key components of the human diet that differ substantially from the diet of other primates, the frequent use of meat of many humans and the cooking of their food which is common for almost all human populations, are modeled in the experiment. I tested for their impact on liver gene expression. I found that both the differences in food substrates - meat and tuber - as well as in their preparation affect gene expression in mice significantly. The effect is bigger between food substrates than between methods of preparation. Differentially expressed genes between food substrates and food preparation were predominantly related to metabolic functions. In addition, immune-genes showed differential expression between the comparisons of raw meat to both, raw tuber and cooked meat, respectively. The results indicate that different food substrates and food preparations activate different metabolic pathways and that the cooking of food and particularly of meat has an influence on the immune also changes immune-reactions of the body. I showed that expression differences in these mice are correlated with the differences observed between humans and other primates, and that there is evidence that adaptation to these diets dates to more than 300.000 years. Finally, I showed that transcription factors play in important role in regulation of gene expression with respect to different food preparation. In the second part I analyzed the expression of one key regulator of gene expression: microRNAs (miRNAs). Using miRNA expression data from multiple primate species and for multiple tissues I found that expression differences vary between tissues. While heart and brain show only few expression differences between primates, other tissues are more variable in expression. The most extreme expression differences in all three primate species were found in the brain, which may reflect the importance of miRNAs in the regulation of gene expression in the brain. Expression differences in testis were significantly larger between humans and macaques than between chimpanzees and macaques, indicating that miRNAs evolved differently in human compared to chimpanzees. MiRNA expression differences were correlated with expression differences of their target genes genome-wide which underlines the regulatory importance of miRNAs. I also showed that differentially expressed miRNAs between species/tissues preferentially targeted transcription factors, which are important gene expression regulators as well. This finding that suggests complex regulatory pathways involving both miRNAs and transcription factors in the control of gene expression. Finally, I used the miRNA sequencing data to annotate new miRNAs in primates and was able to increase the number of annotated miRNAs substantially, especially for the non-human primates which were previously not extensively annotated. The overlap of miRNAs annotated in multiple primate species thereby also increased which will support future studies to investigate the evolutionary changes of miRNAs between these primates.

Esta investigación se basa en los problemas detectados en la reproducción y desarrollo de los grandes simios y específicamente en los gorilas de las poblaciones que se mantienen ex situ dentro del proyecto de conservación Europeo (EEP. EAZA), y la necesidad de investigar factores que puedan mejorar su éxito reproductivo y su desarrollo. Los sujetos del estudio son miembros de una mega población que ha vivido a lo largo de varias décadas, y en algunos casos aún vive, en cautividad y, por tanto, en unas condiciones que difieren bastante de las propias de la especie en su medio natural tanto en lo concerniente a su hábitat, condiciones sociales y condiciones demográficas. Uno de los problemas específicos detectados en las poblaciones de grandes simios proviene del considerable número de individuos criados por humanos que existe en la población histórica y actual, y que presentan deficiencias en la conducta materna, en las relaciones sociales, y en la reproducción (en su término más amplio, no el mero hecho del apareamiento). Es por ello que se revisan aspectos del proceso de socialización, y de las conductas sociales haciendo una especial incidencia en los factores que influyen en la conducta materna, así como en los factores que pueden favorecer la reproducción en adultos que en fases iniciales de su desarrollo no tuvieron la oportunidad de socializarse de forma adecuada a la especie. Los estudios realizados se basan en el resultado de cuestionarios, observaciones cualitativas de ciertas conductas sociales y datos demográficos y específicos obtenidos del Studbook Europeo de Gorilas. Los resultados amplian el conocimiento sobre la adquisición de conductas sociales en los grandes simios en general, y en los gorilas en particular, y contribuyen a la mejora en la gestión de los programas de conservación ex situ. La investigación permitió identificar aquellos factores que favorecen un perfil maternal adecuado en las hembras de gorila cautivas, y por extensión en otras especies de grandes simios, poniendo de manifiesto los factores que afectan al desarrollo social de los gorilas criados por humanos y determinando cuáles son las circunstancias necesarias para realizar la introducción temprana de dichos individuos en un grupo de coespecíficos, de modo que su perfil social sea satisfactorio y puedan ser introducidos sin dificultad en otros grupos de coespecíficos al alcanzar la madurez sexual. Asimismo, se comprobaron los resultados reproductivos de la población de los individuos criados por humanos, y por tanto su contribución a la población total, y se determinaron circunstancias que podían favorecer su reproducción al alcanzar la madurez sexual. / Incidental factors in the reproduction and development of primates in captivity: Western gorillas " ex-situ " conservation (Gorilla gorilla gorilla) Authoress: Ma. Teresa Abelló Poveda Director(Principal) of the Thesis: Dra. Montserrat Colell Mimó TEXT: This research is based on the problems detected in the reproduction and development of great apes and specifically on the ex situ gorilla population (EEP. EAZA), and the need to investigate factors that could improve their breeding success and their development. The subjects of this study are members of a gentle population who has lived throughout several decades, and in some cases still it lives, in captivity and, therefore, under conditions that defer enough from their natural ones in the wild regarding habitat and social life. One of the specific problems detected in the great apes population comes from the considerable number of individuals hand-raised (by human beings) that exists in the historical and current population, and that present some deficiencies in their maternal behaviour, in their social relations, and in their breeding results. For that reason different aspects of the socialization process and social behaviour are analyzed on hand-reared animals, with special incidence on the factors that have some influence on maternal behavior and a successful breeding of individuals when reaching their sexual maturity. The different studies presented are based on the result from surveys (quantitative data), qualitative observations of social behaviour and specific demographic data obtained from the Gorilla European Studbook. The results give a better knowledge a on the acquisition of socila skills on great apes, and more specifically on gorillas, and it is worth to improve exsitu conservation (management/breeding) programmes This research allowed allowed to identify those factors that favor a good maternal profile in captive gorilla females, and for extension in other species of great apes. Revealing some factors of concern for the social development of hand-reared gorillas and determining which are the necessary circumstances to realize the early introduction of the above mentioned individuals in a group of coespecíficos, so that their develop with a adequate social profile and can be introduced without difficulty in other groups of coespecíficos

This thesis reports on cross-sectional surveys aimed at detecting and characterizing haemoprotozoan parasites infecting wild free-ranging non human primates (NHPs) in Kenya, East Africa. Blood samples from olive baboons (Papio cynocephalus anubis), vervet monkeys or African green monkeys (AGMs, Chlorocebus aethiops) and Syke's monkeys (Cercopithecus mitis) from five provinces of Kenya were analyzed. The haemoprotozoan parasites survey was performed with microscopic evaluation of blood smears, serological techniques and molecular tools. Blood specimens and serum samples from 121 NHPs were tested for the presence of Trypanosoma brucei (Study I). Indirect antibody enzyme-linked immunosorbent assay (Ab-ELISA) detected titers of anti-T. brucei antibodies in 19% (23/121) of the sera sampled. Subsequent field-oriented latex agglutination test (LAT) detected presence of T. brucei antigens in 16% (19/121) of the sera. However, there were no active infections detected on fixed blood smears, or wet blood films. Of the 378 NHPs sera samples tested for Leishmania major exposure using Ab-ELISA, 66% had detectable anti-L. major antibodies (study II). Western blot (WB) assay detected anti-L. major antibodies in sera from 46% (175/378) of the NHPs samples. Specific proliferation of peripheral blood mononuclear cells to L. major antigen was demonstrated in 23% (17/57) of AGMs samples. Haemoprotozoan parasites, Entopolypoides macaci and Hepatocystis kochi were detected by microscopic evaluation of Giemsa-stained blood smears from 179 NHPs (study III). The prevalence rate of E. macaci was 43% in African green monkeys, 35% in Syke’s monkeys and 33% in baboons. H. kochi infection rate was 18% in African green monkeys, 23% in baboons and 25% in Syke’s monkeys. Subsequent indirect immunofluorescent antibody test (IFAT) supported the morphologic appearance of E. macaci observed by microscopy. Molecular tools were used to detect and identify haemoprotozoan parasites in wild free-ranging NHPs (study IV). Nested polymerase chain reaction (PCR) targeting Babesia β-tubulin gene detected a 22% (27/125) B. microti infections in free-ranging NHPs in Kenya. PCR also detected 22% mixed infections by Hepatocystis and Entopolypoides, 12% Hepatocystis and Babesia and 7% Entopolypoides and Babesia (study V). Phylogenetic analysis inferred from mitochondrial cytochrome b (Cyt-b) gene confirmed the presence of Hepatocystis kochi whereas analysis of 18SS rRNA gene confirmed presence of two piroplasms, Babesia sp. and Entopolypoides macaci. In conclusion, epidemiological results from sero-prevalence studies provide strong circumstantial evidence that some species of Kenyan NHPs are naturally exposed to L. major and T. brucei infections and could be potential reservoir hosts for these haemoparasites. Molecular diagnosis revealed the occurrence of mixed parasite infections and confirmed the circulation of Babesia and Entopolypoides species in the same populations of Kenyan NHPs.