We present techniques for joint modeling of binomial and rank response data using the Bayesian paradigm for inference. The motivating application consists of results from a series of assessments on several primate species. Among 20 assessments representing 6 paradigms, 6 assessments are considered to produce a rank response and the remaining 14 are considered to have a binomial response. In order to model each of the 20 assessments simultaneously, we use the popular technique of data augmentation so that the observed responses are based on latent variables. The modeling uses Bayesian techniques for modeling the latent variables using random effects models. Competing models are specified in a consistent fashion which easily allows comparisons across assessments and across models. Non-local priors are readily admitted to enable more effective testing of random effects should Bayes factors be used for model comparison. The model is also extended to allow assessment-specific conditional error variances for the latent variables. Due to potential difficulties in calculating Bayes factors, discrepancy measures based on pivotal quantities are adapted to test for the presence of random effects and for the need to allow assessment-specific conditional error variances. In order to facilitate implementation, we describe in detail the joint prior distribution and a Markov chain Monte Carlo (MCMC) algorithm for posterior sampling. Results from the primate intelligence data are presented to illustrate the methodology. The results indicate substantial paradigm-specific differences between species. These differences are supported by the discrepancy measures as well as model posterior summaries. Furthermore, the results suggest that meaningful and parsimonious inferences can be made using the proposed techniques and that the discrepancy measures can effectively differentiate between necessary and unnecessary random effects. The contributions should be particularly useful when binomial and rank data are to be jointly analyzed in a parsimonious fashion.

<p>Deciphering the molecular mechanisms driving the phenotypic differences between humans and primates remains a daunting challenge. Mutations found in protein coding DNA alone has not been able to explain these phenotypic differences. The hypothesis that mutations in non-coding regulatory DNA are responsible for altered gene expression leading to these phenotypic changes has now been widely supported by differential gene expression experiments. Yet, comprehensive identification of all regulatory DNA elements across different species has not been performed. To identify the genetic source of regulatory change, genome-wide DNaseI hypersensitivity assays, marking all types of active gene regulatory element sites, were performed in human, chimpanzee, macaque, orangutan, and mouse. Many DNaseI hypersensitive (DHS) sites were conserved among all 5 species, but we also identified hundreds of novel human- and chimpanzee-specific DHS gains and losses that showed signatures of positive selection. Species-specific DHS gains were enriched in distal non-coding regions, associated with active histone modifications, and positively correlated with increased expression - indicating that these are likely to be functioning as enhancers. Comparison to mouse DHS data indicate that human or chimpanzee DHS gains are likely to have been a result of single events that occurred primarily on the human- or chimpanzee-specific branch, respectively. In contrast, DHS losses are associated with events that occurred on multiple branches. At least one mechanism contributing to DHS gains and losses are species-specific variants that lead to sequence changes at transcription factor binding motifs, affecting the binding of TFs such as AP1. These variants were functionally verified by DNase footprinting and ChIP-qPCR analyses.</p> / Dissertation

Doctor of Philosophy (PhD) / Background: The development of the blood supply in the primate retina has been extensively studied; however the relationship of the differentiating retina to the choroidal blood supply is less well known. The interaction of astrocytes and vascular endothelial cells promotes the development of the retinal vasculature from 14 weeks’ gestation (WG). Initially, astrocytes lead the developing capillaries from the optic nerve towards the macular area. However, neither astrocytes nor endothelial cells enter a prescribed avascular area, within which the fovea later forms. This may be attributed to expression of a factor that inhibits astrocyte and endothelial cell proliferation in the fovea. A factor found in the CNS that is already known to have these effects is transforming growth factor-β (TGF-β). Aims: This thesis investigated the relationship between retinal maturation and choroidal blood vessel supply and the possible role for TGF-β as an antiangiogenic factor in maintaining an avascular fovea during primate retinal development. Methods: Human eyes between 11 WG and 40 years were obtained with ethical approval from Prince of Wales Hospital and the NSW Lions Eye Bank and fixed and sectioned for histological procedures or prepared for polymerase chain reaction (PCR). Macaque eyes from foetal day (fd) 64 to postnatal 11years (p11y) were obtained from Bogor Agriculture University, Indonesia with the approval of the Ethics Committee of the University of Washington, Seattle, USA. Macaque eyes were also fixed and sectioned for immunohistochemistry and in situ hybridisation. RNA was extracted from human foetal retinas and used for RTPCR (Reverse Transcriptase PCR), QPCR (Quantitative PCR) and preparation of riboprobes. PCR products were analysed using both restriction digest and sequencing. RTPCR was used to identify TGF-β1, TGF-β2 and TGF-β3 in the developing human and in the developing and adult macaque retinas whilst QPCR was used to quantify the TGF-β isoforms in central compared to peripheral retina and in foetal compared to adult retina. In situ hybridisation was performed according to a standard protocol and visualised using Roche HNPP Fast Red detection set with designed riboprobes for TGF-β1, TGF-β2 and TGF-β3 (DIG RNA labelling kit). Some sections were counterstained with vimentin antibody. Immunohistochemistry was performed on human retina and choroid sections using antibodies to CD34 and Ki67 and on human and macaque retina using antibodies to synaptophysin, vimentin, GFAP, calbindin, S-opsin, RG-opsin, rhodopsin, TGF-β1, TGF-β2, TGF-β3 and their receptors TβRI and TβRII. Sections of the retina were imaged and analysed using either a Leica Confocal microscope and TCSNT software or Zeiss Confocal microscope and LSM 5 Pascal software. Data from the human retina and choroid sections corresponding to different regions (foveal, parafoveal nasal, parafoveal temporal, nasal and temporal) was collected to measure the number of Ki-67 immunolabelled mitotic endothelial cells and the area of CD34 immunolabelled choriocapillaris using Adobe Photoshop version 5.0.2, NIH software version 1.62 (measurement macros) and Excel. In the human and macaque sections the intensity of TGF-β protein and mRNA expression was captured from different regions of the retina (foveal, parafoveal nasal, parafoveal temporal, nasal, temporal, nasal to disc) to compile montages. Montages were then re-imported into LSM 5 Pascal software to measure the optical density across each montage along the ganglion cell layer, outer neuroblastic zone and photoreceptor layer collecting data in Excel for graphical representation. In addition to the montages, individual sections were assessed for co-localisation of TGF-β and TβR to various retinal cell types. Results: Analyses of choriocapillaris area and endothelial cell (EC) proliferation were able to demonstrate that the area of choriocapillaris endothelium is greater in the foveal region at all ages (14-18.5WG), that the rate of choriocapillaris EC proliferation declines dramatically over this same period and that the lowest rates of EC proliferation are at the incipient fovea. Most importantly these findings indicate that EC proliferation in the choriocapillaris does not appear to be promoted by increased metabolic activity in central retinal neurons which are more developed with higher oxygen and nutrient demands, which is the mechanism widely thought to regulate development of the retinal vasculature. PCR showed all TGF-β isoforms to be present in the human developing and adult retina. QPCR revealed that TGF-β2 was the most predominant isoform, followed by TGF-β3 with very small amounts of TGF-β1 seen. The isoforms were more abundant in developing rather than adult retina and in central rather than peripheral retina. Studies of the distribution of TGF-β protein and mRNA using immunohistochemistry and in situ hybridisation confirmed the low levels of TGF-β1 protein and mRNA observed in QPCR and demonstrated distinct centroperipheral gradients in the photoreceptor layer for TGF-β2 and TGF-β3. Relative high amounts of TGF-β in the fovea could affect vascular patterning due to TβRI seen in astrocytes which lead the blood vessels at the foveal rim at the level of the ganglion cell plexus. TGF-β2 and TGF-β3 expression is detected before formation of the foveal avascular zone (FAZ) at fd64 (~15WG) - fd73 (~17WG) with levels peaking in the foveal region at fd105 (~25WG) by the time the FAZ forms. Conclusions: This thesis has shown that EC proliferation in the choriocapillaris does not appear to be promoted by increased metabolic activity in central retinal neurons as reduced rates of EC proliferation in the ‘foveal’ chorioretinal location were observed at all ages studied between 14 and 18.5WG. The findings suggest that mechanisms regulating proliferation and growth of the choroidal vasculature are independent of differentiation in the neural retina and are therefore different to those governing the formation of the retinal vasculature. All TGF-β isoforms are expressed in developing and adult human and macaque retina with TGF-β2 being the predominant isoform. TGF-β isoforms are more abundant in central compared to peripheral retina and in developing compared to adult retina. Centro-peripheral gradients of TGF-β2 and TGF-β3 across the photoreceptor layer and TβRI on astrocytes support the presence of TGF-β in the fovea as an antiproliferative and antiangiogenic factor by helping to define the FAZ early in development, well before 23-25 WG in humans and before fd100 in macaques.

abstract: Unanswered questions about the evolution of human gender abound and are salient across the anthropological disciplines and beyond. Did adult sex-typed behavioral tendencies actually evolve? If so, when? For what purpose? The best way to gain insight into the evolution of human gender is to understand the evolution and development of sex-typed behavior in comparative primate taxa. Captive research indicates that there are many proximate factors likely to shape the development of sex-typed behavior in non-human primates&mdash;prenatal and postnatal endocrinological experience, social experience, ecological factors, and their interactions. However, it is largely unknown how sex-typed behavior proceeds and is shaped by those factors in evolutionarily salient environments. This study investigated one&mdash;whether extrinsic sexually differentiated social interactions are likely influential in the development of adult sex-typed behavior in wild-living Lemur catta. Little is known about sex-typed development in this species or in strepsirrhines in general. This research therefore addresses an important phylogenetic gap in our understanding of primate sex-typed development. Behavioral observations were carried out on mixed cross-sectional sample of adult females (n=10), adult males (n=8), yearling females (n=4), yearling males (n=4), and newborn females (n=16) and males (n=14) at Beza Mahafaly Special Reserve in southwest Madagascar from September 2008 to August 2009. Twenty-three sex-typed behaviors were identified in adults using linear mixed effects models and models of group response profiles through time. Of those, only eight had a pre-pubertal developmental component. Infants did not exhibit any sex differences in behavior, but juveniles (prepubertal, weaned individuals) resembled adults in their (relatively few) patterns of expression of sex-typed behavior. Most adult sex-typed behaviors in this species apparently develop at or after puberty and may be under gonadal hormone control. Those that develop before puberty do not likely depend on extrinsic sexually differentiation social interactions for their development, because there is no clear evidence that infants and juvenile male and females are not treated differently by others according to sex. If sexually differentiated social interactions are important for sex-typed behavioral development in subadult ,italic>Lemur catta, they are likely intrinsically (rather than extrinsically) driven. / Dissertation/Thesis / Ph.D. Anthropology 2012

The Becker-DeGroot-Marschak method (BDM) is an auction-like mechanism widely used in behavioural economics, marketing research, and, more recently, in neuroimaging studies of human decision making. The BDM has never been used with animal subjects before, yet its application in monkeys would allow for comparison of studies across species while providing a direct measure of what a reward is worth to a monkey in a single experimental trial. In the BDM, a subject is given a budget with which they can place a bid for some reward, and a computer then randomly selects a competing bid. If the subject’s bid is higher than the computer’s bid then the subject pays an amount equal to the computer’s bid, receives the reward object, and gets to keep the remaining budget. If the subject’s bid is lower than the computer’s bid, the subject does not gain the reward object but retains the entire budget. To adapt the task for monkeys, two rhesus macaques were taught to use water as a budget, and to use a joystick to place a bid in terms of this budget for different volumes of fruit-juice reward. The BDM ensures that the subject’s optimal action is to place a bid equal to their value for the reward-object. This property of truthful value revelation is the BDM’s most important feature in the context of value-based decision making. Currently, the only method of eliciting a monkey’s value for one reward in terms of another depends upon inference of the magnitudes at which the two rewards are chosen with equal probability. Using this ‘binary-choice’ method, many trials are needed to infer a single value: pairwise comparisons of many different magnitudes must be made and choices of each pair must be repeated so that the probability of choosing a reward can be estimated. In contrast, the BDM provides a direct measure of the monkey’s value for the reward as they explicitly state this value on each trial by selecting an equivalent bid. Therefore, the BDM more efficiently utilises the limited time in which a monkey’s behaviour can be assessed in each experimental session, as animals lose the motivation to participate when they become sated. The thesis summarised here describes the training and performance of two rhesus macaques on a novel version of the BDM, specifically designed for a subject that cannot be instructed on the optimal strategy. The technical steps and intermediate tasks that are needed to train a monkey to flexibly place bids by operating a joystick are also detailed, as well as the development of different versions of the task over three years of testing. The results of the final version of the BDM are then presented for both monkeys, showing rational bidding behaviour consistent with an understanding of the method’s contingencies. Theoretical concerns and limitations of the BDM in such a setting are also discussed and the thesis outlines how future experiments can make use of and adapt this version of the BDM for neuronal recording experiments.

abstract: Craniofacial morphology in primates can vary on the basis of their diet because foods are often disparate in the amount and duration of force required to break them down. Therefore diet has the potential to exercise considerable selective pressure on the morphology of the masticatory system. The zygomatic arch is a known site of relatively high masticatory strain and yet the relationship between arch form and load type is relatively unknown in primates. While the relative position and robusticity of the arch is considered a key indicator of craniofacial adaptations to a mechanically challenging diet, and central to efforts to infer diet in past species, the relationships between morphology and diet type in this feature are not well established. This study tested hypotheses using two diet categorizations: total consumption percent and food material properties (FMPs). The first hypothesis that cortical bone area (CA) and section moduli (bone strength) are positively correlated with masticatory loading tests whether CA and moduli measures were greatest anteriorly and decreased posteriorly along the arch. The results found these measures adhered to this predicted pattern in the majority of taxa. The second hypothesis examines sutural complexity in the zygomaticotemporal suture as a function of dietary loading differences by calculating fractal dimensions as indices of complexity. No predictable pattern was found linking sutural complexity and diet in this primate sample, though hard object consumers possessed the most complex sutures. Lastly, cross-sectional geometric properties were measured to investigate whether bending and torsional resistance and cross-sectional shape are related to differences in masticatory loading. The highest measures of mechanical resistance tracked with areas of greatest strain in the majority of taxa. Cross-sectional shape differences do appear to reflect dietary differences. FMPs were not correlated with cross-sectional variables, however pairwise comparisons suggest taxa that ingest foods of greater stiffness experience relatively larger measures of bending and torsional resistance. The current study reveals that internal and external morphological factors vary across the arch and in conjunction with diet in primates. These findings underscore the importance of incorporating these mechanical differences in models of zygomatic arch mechanical behavior and primate craniofacial biomechanics. / Dissertation/Thesis / Appendix A / Appendix B / Appendix D / Doctoral Dissertation Anthropology 2017

In this dissertation I will consider the extent to which our ethical actions are determined by evolution, as well as the consequences of a view that holds that ethical behaviour arose from evolutionary processes. I will further investigate whether evolution can supply a complete account of ethics in the physical world, without sacrificing human freedom and rationality. To do this, I will start by considering the possible negative consequences of applying evolution to human behaviour, in the forms of Social Darwinism and eugenics. I will argue that while these systems of thought are ethically and scientifically unsound, there is strong evidence for the evolutionary origins of ethics, where ethics can be seen as an adaptation that offers a benefit to the individual exhibiting this behaviour. This view is supported by sociobiology, studies in primate behaviour and neuroscience. The implications of ethics as an evolutionary adaptation will be compared to Kantian morality, which is premised on freedom and autonomy, which I will argue are inconsistent with some scientific explanations. While an evolutionary account of ethics can lead to a deterministic view of our behaviour, new developments in neuroscience claim that freedom is an evolutionary adaptation. This naturally developed freedom, combined with self-consciousness, can supply us with an evolutionary account of ethics that does not need augmentation from transcendental principles. / Dissertation (MA)--University of Pretoria, 2014. / lk2014 / Philosophy / MA / Unrestricted

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13112号 / 論医博第2130号 / 新制||医||1022(附属図書館) / (主査)教授 浅野 雅秀, 教授 瀬原 淳子, 教授 近藤 玄 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

付記する学位プログラム名: 霊長類学・ワイルドライフサイエンス・リーディング大学院 / 京都大学 / 新制・課程博士 / 博士(理学) / 甲第24780号 / 理博第4974号 / 新制||理||1710(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 明里 宏文, 准教授 足立 幾磨, 教授 平田 聡 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

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