In most organisms the cellular response to hypoxia is mediated by the master regulator hypoxia-inducible factor-1 (HIF-1). Zebrafish embryos can also arrest development (suspended animation) to tolerate low oxygen. I tested the hypothesis that induction of HIF-1 and associated target genes (eg. erythropoietin) during embryonic development would alter the hypoxia tolerance phenotype of larval and adult fish. I exposed zebrafish embryos at 3 developmental stages to acute (4 h) bouts of hypoxia (5% dissolved oxygen, DO) or anoxia (<0.5% DO). I found that embryos that mount a HIF-1 response have a greater hypoxia tolerance as larvae. Additionally, populations that experienced embryonic HIF-1 induction show an increase in the proportion of males (~70% male), that are more hypoxia tolerant than female fish, compared to control populations (~45% male). Overall, induction of HIF-1 during ontogeny alters the larval and adult zebrafish phenotype to better tolerate future hypoxic bouts. / NSERC

Evolution of adaptation requires both generation of novel phenotypic variation and retention of a locally beneficial subset of this variation. Such retention can be facilitated by genetic assimilation, the accumulation of genetic and molecular mechanisms that stabilize induced phenotypes and assume progressively greater control over their reliable production. A particularly strong inference into genetic assimilation as an evolutionary process requires a system where it is possible to directly evaluate the extent to which an induced phenotype is progressively incorporated into preexisting developmental pathways. Evolution of diet-dependent pigmentation in birds-where external carotenoids are coopted into internal metabolism to a variable degree before being integrated with a feather's developmental processes-provides such an opportunity. Here we combine a metabolic network view of carotenoid evolution with detailed empirical study of feather modifications to show that the effect of physical properties of carotenoids on feather structure depends on their metabolic modification, their environmental recurrence, and biochemical redundancy, as predicted by the genetic assimilation hypothesis. Metabolized carotenoids caused less stochastic variation in feather structure and were more closely integrated with feather growth than were dietary carotenoids of the same molecular weight. These patterns were driven by the recurrence of organism-carotenoid associations: commonly used dietary carotenoids and biochemically redundant derived carotenoids caused less stochastic variation in feather structure than did rarely used or biochemically unique compounds. We discuss implications of genetic assimilation processes for the evolutionary diversification of diet-dependent animal coloration.

When considering the array of terrestrial locomotor behaviors, bipedalism is a particularly rare way of moving about the landscape. In fact, humans are the only obligate terrestrial mammalian bipeds. Therefore, understanding both how and why it evolved is particularly intriguing. However, there is debate over why the evolution of bipedalism occurred and there is a large gap in knowledge for the mechanisms that underpin the evolution of these adaptive morphologies. One complicating factor for sorting out which models best explain how our hominin ancestors became bipedal is that they all rely on the same set of traits. Moreover, many of the traits that are thought to be diagnostic of bipedalism are only linked by association and have not been experimentally tested. That is, they do not appear in non-human primates and other quadrupeds. Therefore, addressing why the evolution of bipedalism occurred requires understanding the adaptive significance of traits linked with bipedalism. In this dissertation, I use an experimental approach employing both human and animal models to explore links between morphology and behavior and to tease apart the adaptive significance of particular traits. For the human portion of the dissertation, I use an inverse dynamics approach (estimating muscle forces from kinematic, kinetic, and anatomical data) to determine how modern human anatomy functions while walking using ape-like postures to clarify the links between morphology and energy costs in different mechanical regimes to determine the adaptive significance of postcranial anatomy. The results from this portion of the dissertation suggest that adopting different joint postures results in higher energy costs in humans due to an increase in active muscle volumes at the knee. These results lead to two conclusions important for understanding the evolution of human bipedalism. One is that human anatomy maintains low energy costs of walking in humans compared to chimpanzees regardless of lower limb postures. Second, the results suggest that erect trunk posture may be an important factor in reducing energy costs, therefore indicating that lumbar lordosis (the curvature of the lower spine) is important for reducing costs. For the animal portion of the dissertation, I use rats as a model for the quadrupedal-to-bipedal transition and experimentally induce bipedal posture and locomotion under a variety of loading conditions to determine if traits consistent with the evolution of bipedalism occur and under what conditions. This experimental design also has the ability to determine if there is a role for developmental plasticity in generating bipedal morphology to help answer the question how the evolution of bipedalism occurred. I find that inducing bipedal behaviors in a quadrupedal animal generates morphology consistent with human bipedal traits and that loading conditions have specific effects in different skeletal elements and at particular joints. I also find that there is a plausible role for developmental plasticity in generating adaptive bipedal morphology in the earliest hominins. Overall, the results from the experimental procedures in this dissertation were able to clarify links between behavior and bipedal morphology, demonstrate a plausible role for developmental plasticity in early adaptation to bipedal behavior in australopiths, determine the adaptive significance of human postcranial anatomy, and the ways in which postcranial anatomy reduces costs.

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This thesis investigates the effects of low oxygen culture conditions and fibroblast growth factor-2 (FGF2) on adult human dermal fibroblasts. It was previously shown that low oxygen and FGF2 culture conditions lead to an extension of proliferative lifespan, low-level activation of stem cell genes, and global transcriptional changes in adult human dermal fibroblasts. Additionally, an increased in vivo tissue regenerative response can be observed when human muscle-derived fibroblasts grown with FGF2 and low oxygen are implanted into mouse muscle injury, leading to a decrease in collagen deposition and scar formation and increase of functional skeletal muscle regeneration, including formation of Pax7+ muscle stem cells. These findings led to an analysis of key cellular oxygen sensors, hypoxia inducible factors (HIFs) and their role in this regenerative response. Directly linking these factors with the regenerative response, I have shown, with knockdown experiments, that HIF-2α is required for the increased proliferative capability and decreased senescence of human dermal fibroblasts (hDFs) induced by hypoxia. I have also determined that low oxygen causes an early and transient increase of HIF-1α and late and sustained increase of HIF-2α protein accompanied by increased nuclear translocation. Using overexpression and knockdown approaches via lent-virus, I determined that HIF-2α appears to modulate FGF2 signaling through the FGF receptors. First, under low oxygen conditions, exogenous FGF2 led to downregulation of endogenous FGF2, which can be mimicked by overexpression of HIF-2α. In ambient oxygen we didn't see this effect. Second, HIF-2α overexpression appears to lead to increases in FGFR1 phosphorylation and consequently increased ERK1/2 phosphorylation, and increases in the expression of heparan sulfate modifying enzymes (NDST1, NDST2, and EXTL2). Lastly, sustained supplementation with FGF2 in low oxygen inhibits receptor-mediated FGF2 signaling. To understand these effects at the transcriptional level, using microarray technology, we identified oxygen-mediated FGF2 effects on genes involved in cell survival and proliferation. Through bioinformatics analyses, I determined that genes involved in wound healing (extracellular matrix genes, adhesion molecules, cytokines) are upregulated in FGF2 treated fibroblasts grown under low oxygen. By utilizing a gain-of-function approach, we were able to assess the effects of altered HIF-2α activity on the expression of Oct4, Sox2, Nanog, Rex1, and Lin28 in adult hDFs. The results indicate that overexpression of the HIF-2α transcription factor increases Oct4 mRNA, but not Oct4 protein, levels, and had no effect on Nanog and Lin28 proteins. HIF-2α overexpression also mediated FGF2 induction of Sox2 and Rex1 proteins of higher molecular weight. This thesis expands our knowledge about effects of low oxygen and FGF2 on adult human dermal fibroblasts and explains in part, how FGF2 under low oxygen conditions may lead to increased proliferation, extended life span, regenerative competency and increased developmental plasticity of adult hDFs.

The Breech Baby Study is a mixed methods study which combines qualitative and quantitative inquiry. This study explores psycho-social-cultural risk factors for breech presentation from an evolutionary perspective. The quantitative component of the study uses Florida birth certificate and Medicaid data sets from 1992-2003 to evaluate the influence of ethnicity and socio-economic status on breech presentation. Ethnicity and socio-economic status account for less than two percent of the variance of risk factors for breech presentation. The qualitative study includes 114 mothers of breech and cephalic presentation babies who completed the State Trait Personality Inventory and a socio-demographic survey. Of these, 52 mothers of cephalic presentation babies and 23 mothers of breech presentation also participated in an in-depth interview about formative life experiences and peri-conception through delivery. The primary data analysis found mothers of breech presentation babies exhibit psycho-social-cultural characteristics unlike those found in mothers of cephalic presentation babies. These characteristics include being idealistic, analytical, polished, overextended, and fearful. Mothers of cephalic presentation babies were better equipped to adapt to unexpected situations and to be pragmatic in the face of unresolvable circumstances. Mothers of breech presentation babies were further separated into two categories. One category is achievement focused woman while the other is non-present focused woman. While both sets of breech presentation mothers were idealistic, the achievement focused mothers were more likely to be analytical, polished, and overextended. In contrast, the non-present focused mothers had a history of abuse and were more likely to have an unresolved pregnancy outcome or to be fearful. Breech presentation is interpreted by attachment theory, evolutionary ecological reproductive theory, and developmental plasticity theory as a fetal strategy to adapt to the intra-uterine relationship environment and an attempt to predict the extra-uterine relationship environment.

abstract: Conditions during development can shape the expression of traits at adulthood, a phenomenon called developmental plasticity. In this context, factors such as nutrition or health state during development can affect current and subsequent physiology, body size, brain structure, ornamentation, and behavior. However, many of the links between developmental and adult phenotype are poorly understood. I performed a series of experiments using a common molecular currency - carotenoid pigments - to track somatic and reproductive investments through development and into adulthood. Carotenoids are red, orange, or yellow pigments that: (a) animals must acquire from their diets, (b) can be physiologically beneficial, acting as antioxidants or immunostimulants, and (c) color the sexually attractive features (e.g., feathers, scales) of many animals. I studied how carotenoid nutrition and immune challenges during ontogeny impacted ornamental coloration and immune function of adult male mallard ducks (Anas platyrhynchos). Male mallards use carotenoids to pigment their yellow beak, and males with more beaks that are more yellow are preferred as mates, have increased immune function, and have higher quality sperm. In my dissertation work, I established a natural context for the role that carotenoids and body condition play in the formation of the adult phenotype and examined how early-life experiences, including immune challenges and dietary access to carotenoids, affect adult immune function and ornamental coloration. Evidence from mallard ducklings in the field showed that variation in circulating carotenoid levels at hatch are likely driven by maternal allocation of carotenoids, but that carotenoid physiology shifts during the subsequent few weeks to reflect individual foraging habits. In the lab, adult beak color expression and immune function were more tightly correlated with body condition during growth than body condition during subsequent stages of development or adulthood. Immune challenges during development affected adult immune function and interacted with carotenoid physiology during adulthood, but did not affect adult beak coloration. Dietary access to carotenoids during development, but not adulthood, also affected adult immune function. Taken together, these results highlight the importance of the developmental stage in shaping certain survival-related traits (i.e., immune function), and lead to further questions regarding the development of ornamental traits. / Dissertation/Thesis / Ph.D. Biology 2012

In autonomous robotics, there is still a trend to develop and tune controllers with highly explicit goals and environments in mind. However, this tuning means that these robotic models often lack the developmental and behavioral flexibility seen in biological organisms. The lack of flexibility in these controllers leaves the robot vulnerable to changes in environmental condition. Whereby any environmental change may lead to the behaviors of the robots becoming unsuitable or even dangerous. In this manuscript we look at a potential biologically plausible mechanism which may be used in robotic controllers in order to allow them to adapt to different environments. This mechanism consists of a hormone driven epigenetic mechanism which regulates a robot's internal environment in relation to its current environmental conditions. As we will show in our early chapters, this epigenetic mechanism allows an autonomous robot to rapidly adapt to a range of different environmental conditions. This adaption is achieved without the need for any explicit knowledge of the environment. Allowing a single architecture to adapt to a range of challenges and develop unique behaviors. In later chapters however, we find that this mechanism not only allows for regulation of short term behavior, but also long development. Here we show how this system permits a robot to develop in a way that is suitable for its current environment. Further during this developmental process we notice similarities to infant development, along with acquisition of unplanned skills and abilities. The unplanned developments appears to leads to the emergence of unplanned potential cognitive abilities such as object permanence, which we assess using a range of different real world tests.

Vision plays a key role in life of many vertebrates, and the performance of visual system is often adapted to specific environments inhabited by individual species. Fish colonized a wide range of habitats and adjusted their visual abilities to maximize their success rates in hunting, reproduction and predator avoidance. This thesis is focused on molecular mechanism of visual system, namely on genes for photoreceptor proteins, opsins, of two major groups of teleost fishes: African riverine cichlids (family Cichlidae, order Cichliformes, part of larger taxa Percomorpha), and European freshwater cyprinids (family Cyprinidae, order Cypriniformes, part of larger taxa Ostariophysi). Two types of photoreceptor cells are present on retina: the cones and the rods. Actinopterygian fishes in general have four cone opsin types (SWS1, SWS2, RH2 and LWS) used for colour (photopic) vision, and one rod opsin type (rhodopsins) for vision in deteriorated light conditions (scotopic vision). In the present thesis, I focus on 1) DNA sequence and amino acid substitutions of the opsin genes, and on 2) gene expression levels of opsins sensitive to various wavelengths of light spectrum. The results of my work show that both cichlids (family Cichlidae) and cyprinids (family Cyprinidae) have a complete set of opsin genes in...

No description available.