The most frequent clinical presentation of peripheral arterial occlusive disease (PAOD) is intermittent claudication, which may be caused by impaired vasodilation. Patients demonstrate both local and systemic impairments in vasodilation, but as the collateral circulation is the primary site of resistance to the ischemic zone, impaired collateral vasodilation would have the greatest potential to induce claudication. Collateral function following arterial occlusion is not well defined, but immature collaterals may demonstrate impaired vasodilation in animal models, although this is potentially improved with exercise training. Furthermore, as females exhibit poorer physical function with ischemia and less improvement with therapeutic exercise, there appears to be a sexually dimorphic response to PAOD, warranting a comparison in collateral vasodilation between sexes. In this study, the femoral artery was ligated to induce chronic ischemia in sedentary and exercise-trained mice, and at 7 or 28 days post-surgery, the diameter of the gracilis collateral arteriole was measured at rest and after gracilis muscle contraction using intravital microscopy. No major sex differences were observed in any group. At day 7, both the resting and dilated diameters were increased, while vascular reactivity was minimal. By day 28, resting diameter decreased while maximal diameter was unchanged, causing an increase in functional vasodilation. Exercise training also improved vasodilation by decreasing collateral resting diameter. These results are consistent with reported trends in endothelium-dependent and smooth muscle-dependent vasodilation, which are impaired in immature vessels and improved with maturation and exercise, but the significance of the observed variations in resting diameter remains unclear. Large resting diameters at day 7 could be due to a loss of sympathetic tone or the proliferative and non-contractile state of smooth muscle cells, while decreased resting diameters at day 28 could indicate that a smooth muscle contractile phenotype has been restored, or that the gracilis collateral is no longer the primary collateral. However, the further research is required to determine the functional relevance of collateral resting diameter and its importance in the ischemic limb circulation.

A l'adolescence, la maturation cérébrale implique des changements anatomiques globaux et régionaux subtils, et estimer la morphologie exacte de certaines structures au cours du développement post-pubertaire est par conséquent difficile. L'effet du dimorphisme sexuel sur la maturation cérébrale n'a été que très peu exploré de façon prospective par l'imagerie par résonance magnétique. Dans ce contexte, ce travail de thèse est consacré à l'étude longitudinale des effets du sexe sur la maturation cérébrale à l'aide de deux méthodes pour contrôler et analyser les variations de positionnement spatial des images acquises à différents intervalles de temps. Dans une première étude utilisant une approche multimodale, notre objectif était d'examiner si le dimorphisme sexuel dans la maturation cérébrale du système limbique pouvait expliquer les différences émotionnelles entre les filles et les garçons pendant l'adolescence. Nous avons adapté pour cela une méthode de traitement longitudinal sur des images anatomiques et de diffusion de 335 adolescents sains entre 14 et 16 ans. Nous avons mis en évidence des différences sexuelles dans la maturation cérébrale du système limbique avec une maturation plus tardive des garçons par rapport aux filles. Ces changements avaient un rôle médiateur sur les différences sexuelles dans la régulation émotionnelle, illustrée par une augmentation des traits de personnalité positifs chez les garçons et une diminution chez les filles. Dans une deuxième étude utilisant une approche originale de recalage, notre objectif était d'estimer et extrapoler des trajectoires de maturation en fonction du dimorphisme sexuel. Nous avons mis en évidence des trajectoires divergentes entre les filles et les garçons entre 14 et 16 ans, illustrant une différenciation des vitesses de maturation croissante à cette période, spécifiquement dans le cortex préfrontal. Ces trajectoires différentielles ont permis d'estimer une avance de maturation de 5 mois chez les filles dans le cortex préfrontal. L'ensemble de ces résultats apporte des informations utiles à une meilleure compréhension des différences de maturation cérébrale entre les filles et les garçons, et de leurs liens avec la dérégulation du système émotionnel et donc la vulnérabilité à la dépression à l'adolescence. / In adolescence, brain maturation involves subtle global and regional anatomical changes, and estimating the exact morphology of some structures during post-pubertal development is therefore difficult. Effect of sexual dimorphism on brain maturation has been under-explored prospectively by magnetic resonance imaging. In this context, this work is focused on the longitudinal study of the effects of sex on brain maturation using two methods to control and analyze the spatial positioning variations of images acquired at different time points. In a first study using a multimodal approach, our goal was to examine sexual dimorphism in brain maturation of the limbic system to explain the emotional differences between girls and boys during adolescence. We adapted a method of longitudinal processing on anatomical and diffusion images of 335 healthy adolescents between 14 and 16 years. We highlighted sexual differences in brain maturation of the limbic system with a later maturation of boys compared to girls. These changes mediated sexual differences in emotional regulation, illustrated by an increase in positive personality traits in boys and a decrease in girls. In a second study using an original registration approach, our objective was to estimate and extrapolate maturation trajectories based on sexual dimorphism. We highlighted divergent trajectories between girls and boys between 14 and 16, illustrating a differentiation in maturation rates that increased during this period, specifically in the prefrontal cortex. These differential trajectories made it possible to estimate a maturational advance of 5 months in girls in the prefrontal cortex. All these results provide useful information for a better understanding of the differences in brain maturation between girls and boys, and their links with the emotional system dysregulation and therefore the vulnerability to depression in adolescence.

Sexual reproduction is an evolutionary innovation that arose 1.2 billion years ago, and in that time, has allowed a rapid diversification of species outpacing that of asexually reproducing organisms. Successful sexual reproduction in animals requires the incredible coordination of complex genetic and behavioral factors; from the most fundamental levels of ensuring correct chromosome segregation and ploidy to the most complex of behavioral mating rituals, any failure can result in a complete loss of evolutionary fitness. In this thesis, I have explored the developmental programs that function to ensure somatic sex determination, sexual differentiation, and mating behaviors in C. elegans. C. elegans is an androdiecious nematode species that has been extensively characterized in regard to the sexual dimorphism of its development, nervous system, and behavioral outputs. Sex determination pathways are widely diverged across phyla, and C. elegans has coopted a Gli family transcription factor to serve as a cell autonomous global regulator of somatic sex determination. I investigated the expression of this transcription factor, tra-1, with cellular, subcellular, sex-specific, and temporal resolution in both sexes of C. elegans and found that it is dynamically regulated to control sex determination. In contrast to the upstream sex determination pathway, genes that control downstream sexual differentiation in animals display much higher functional conservation, and many of the regulators of sexual differentiation belong to a family of transcription factors known as the DMRT family. Downstream of the tra-1 global regulator, I found that the highly conserved DMRT family gene dmd-4 acts much more specifically in adult hermaphrodites to generate sexual dimorphism at the level of the phasmid sensory neurons PHA and PHB. Furthermore, the sexual dimorphism of DMD-4 is regulated post-translationally by a ubiquitin-binding domain that I also found to be functionally conserved in the human ortholog, Dmrt3. Although these transcription factors both demonstrate the high degree of genetic control that contributes to sex determination and sexual differentiation, I also described male-specific effects of early life stress on sexual dimorphic synaptic connectivity and behavior generated by the phasmid sensory neurons, indicating that sexual differentiation is also plastic to environmental cues encountered during the life of an organism. This thesis provides insight into how genetic pathways function at multiple levels to give rise to extensive sexual dimorphism in the soma of an animal, both globally and in regard to the development on individual cells, in addition to the ways in which these genetic pathways can be modified by environmental factors and organismal life history.

5 Abstract Morphological traits give information about the adaptations of the studied species, the resources, which it uses, and they can generally tell us about the use of ecological space. Intraspecific morphological variability reflects various adaptations of local populations thus variability reflect different way of life. The subject of this thesis is an ecologically interesting group of specialized tropical songbirds - Sunbirds (Nectarinidae). The taxon exhibits number of adaptations to specific food collecting a combination of nectarivory and insect hunting. I focused here on the intraspecific variability of three species (Cyanomitra oritis, Cinnyris reichenowi and C. bouwieri) living in different habitats in Cameroon. The aim of this work was to find out in what morphological characters are this species sexually dimorphic. Furthermore, if their populations living in remote locations differ? Finally, if all studied species show similar trend of intraspecific variability of the traits, which could have common ecological causes. The following traits were measured: wing and tail feather length, beak dimensions, total body weight and other characters. The analysis is based on field data collected between 2003 and 2015 and museum collections. Overall, we collect information about ca. 1200 individuals for...

The use of the Daubert Standard in court proceedings has highlighted the need to substantiate scientific findings or claims beyond simply accepting the word of a respected expert. The concept of postmenopausal masculinization of the skull in female crania falls into this category. Dr. Walker references this concept in several articles but there is no research to support this hypothesis. This project examines the theory of postmenopausal masculinization of female crania from several perspectives, using the visual sex estimation method set forth in Standards for Data Collection from Human Skeletal Remains edited by Jane E. Buikstra and Douglas H Ubelaker, photographic seriation of these sex estimation traits, and metric measurements in conjunction with Fordisc 3.1. A sample of 395 crania from the Hamann-Todd Collection at the Cleveland Museum of Natural History was analyzed using all three of these methods to determine if there was a pattern of masculinization in the postmenopausal female sample. The average age for the onset of menopause in the United States is 50, thus there should be an increase in "masculinization" observable through more rugged sex estimation traits, a higher number of females 50 or over being found below the midpoint in photographic seriations of sex estimation traits, and an increase in Fordisc 3.1 sex identification misclassifications in females in this age category. The results of the analyses revealed that there were statistically significant differences between ancestry groups, the sexes, and in some cases, age-groups. The results of this research indicate that though there are some differences between comparison groups, there does not appear to be a cohesive pattern of masculinization in female crania at or after the average age of onset of menopause. Human variation is endless, and even in areas of the skeleton for which it has been established that there is a significant degree of sexual dimorphism, there will be individuals who do not fit neatly into a binary conception of sexual divergence. Though these individuals may be misidentified as the opposite sex using one or all of the methods utilized in this project, this falls short of being classified as a part of the menopausal process in females.

The sex-dependent pituitary growth hormone (GH) secretory profiles, pulsatile in males and persistent in females, regulate sex-biased expression of hundreds of genes in mammalian liver, contributing to sex differences in hepatic metabolism and disease. The sex-biased GH actions in the liver are mediated by STAT5b and enhanced by a network of transcription factors including the male-biased BCL6 and the female-specific CUX2, acting in the context of sex-biased chromatin states. First, the transcriptional and epigenomic changes induced by continuous-GH infusion (cGH) in male mice, which rapidly feminizes the temporal profile of liver STAT5 activity, were examined. RNA-seq analysis determined that cGH repressed the majority of male-biased genes and induced most female-biased genes within 4-days; however, several highly female-specific genes showed partial feminization. Female-biased genes already in an active chromatin state in male liver were induced early; genes in an inactive chromatin state often responded late. Early cGH-responsive genes included Cux2 and Bcl6 and their targets. DNase-seq and ChIP-seq were used to identify changes in sex-specific chromatin accessibility and histone modifications accompanying these cGH-induced gene expression changes. H3-K27me3 is a key sex-biased repressive mark found preferentially at highly female-biased genes in male mouse liver. Consistently, induction of female-biased genes by cGH was associated with loss of H3-K27me3 at their gene bodies. H3K27 methylation is catalyzed by Polycomb Repressive Complex-2 (PRC2) through its homologous catalytic subunits EZH1 and EZH2. An Ezh1-knockout mouse model with a hepatocyte-specific knockout of Ezh2 (DKO) was used to further investigate the role of H3-K27me3 in repressing sex-biased genes in mouse liver. Loss of Ezh1/Ezh2 led to a significant decrease in sex-specific gene expression, with many female-biased genes induced and male-biased genes repressed. These gene responses were more extensive in male than female liver, as was the loss of H3K27me3 sites and the reciprocal increases in active histone marks. There was substantial up-regulation of liver cancer and liver fibrosis-related genes in male and female DKO-mouse liver, with a subset of genes preferentially up-regulated in females. Thus, GH regulated sex-biased liver physiology is dictated by transcription factors arranged in a hierarchical network and by dynamic sex-biased epigenetic states. / 2020-06-12T00:00:00Z

Understanding the maintenance of sexual systems is of great interest to evolutionary and ecological biologists because plant systems are extremely varied. Plant sexual systems have evolved to include not only complete plants with both male and female reproduction occurring on one plant (i.e., monoecious and hermaphroditic) but also plants with male and female function on separate plants (dioecious). The dioecious reproductive system can be used to test theories on niche differentiation given that having separate plants potentially allows for the exploitation of a broader niche. This increase in the realized niche is due to the ability for separate sexes to occupy different niches, which may occur in different physical habitats. Some dioecious plants have been shown to occur in areas biased to nearly 100% male or nearly 100% female, called spatial segregation of the sexes (SSS). Occupying a broader niche could increase fitness in some species when the separation is used for one sex to gain access to resources that increase reproductive success and/or if the separation inhibits deleterious competition. These two mechanisms have been previously proposed for the evolution of SSS in dioecious plants. The first mechanism suggests that males and females have evolved to occupy different niches due to differences in reproduction (sexual specialization). The hypothesis for the sexual specialization mechanism is that females should have higher fitness in female-majority sites and males should have higher fitness in male-majority sites. The second mechanism states that males and females occupy different niches due to competition between the sexes (niche partitioning). The hypothesis for niche partitioning states that inter-sexual competition should decrease fitness more than intra-sexual competition. These mechanisms are not mutually exclusive. In our research we use the salt-marsh grass Distichlis spicata as our study species because this plant is dioecious and because molecular markers have been developed to determine the sex of juvenile plants. These molecular markers are important for testing the niche partitioning hypothesis for SSS in juveniles. Furthermore, previous work in California has shown that plants occur in areas nearly 100% female and nearly 100% male called spatial segregation of the sexes (SSS). The previous research also showed that female-majority sites were higher in soil phosphorus than male-majority sites. We conduct all research, presented in the proceeding chapters, on Distichlis spicata in the Sand Lake estuary near Pacific City, Oregon and in the laboratory at Portland State University. In Chapter 1 we used field data to answer two questions: (1) Does Distichlis spicata exhibit SSS in Oregon, and (2) If SSS is occurring, do differences occur in plant form and function (sexual specialization) in reproductive female and male plants in female-majority and male-majority sites? We used a sex ratio survey and collected field data on reproductive males and females. Our results show that there are female-majority and male-majority areas and SSS is occurring in the Sand Lake Estuary. Results from our native plant data suggest that reproductive females perform better in female-majority sites compared to male-majority sites which could suggest that sexual specialization is occurring in females. We currently have a long term field reciprocal transplant experiment in place to further address this hypothesis. In Chapter 2 we use field dada to address the following questions: (1) Does site-specific soil nutrient content occur in August, when females have set seed? (2) Does sex-specific mycorrhizal colonization occur in reproductively mature plants? (3) Does sex-specific mycorrhizal colonization vary seasonally in natural populations? Inside the roots of D. spicata a symbiotic relationship is formed between plant and arbuscular mycorrhizal fungus (AM). The AM- plant relationship has been shown to thrive in phosphorus limited areas because the mycorrhizal fungus increases nutrient access to the plant. We analyzed the results of the field soil nutrient content and mycorrhizal colonization in roots of native Distichlis spicata from male-majority and female-majority sites. The root colonization included staining roots with trypan blue and viewing sections of the roots under the microscope. Our results show that female- majority sites are higher in phosphorus and are found to have higher AM colonization than male- majority sites in the field. In Chapter 3 we then reciprocally transplanted D. spicata plants in the field to address the following questions: (1) Does niche partitioning occur in D. spicata, and (2) If niche partitioning is occurring, which plants are competing more? Our reciprocal transplant experiment included seeds grown in intra-sexual, inter-sexual and no competition in cones, planted directly into the field, and allowed to grow for 15 months. After the 15 months was over we measured survival, dry weight and root/shoot ratio. The design of the experiment was to determine the effects of competition (intra-sexual and inter-sexual) and no competition on (single male and female) on survival, biomass and root/shoot ratios. Our results show that niche partitioning is occurring and plants in inter-sexual competition have significantly less biomass then intra-sexual competitors. In, Chapter 4, we conduct a laboratory experiment to address the following questions: (1) Do plants show plasticity in their response to root exudates of the competing plant in regards to the sexual phenotype of the competitor? (2) Do plants show plasticity in their response to root exudates of the competing plant with respect to the relatedness of the competitor? We use sterile seeds grown in 24-well plates containing liquid media. For each competing plant, we picked plants up out of the wells and into the competing plants wells so that plants only experienced media that the competing plant had grown. At no time do roots ever come into contact with one another. We measured primary root length, number of lateral roots, the number of root hairs, root/shoot ratio and total dry weight. We analyzed the study two different ways, one for sexual type competition (inter-sexual, intra-sexual, none) and for plant relationship (KIN, STRANGER and OWN). The results for the sexual type competition found that inter-sexual competition was greater for root/shoot ratio and dry weight. The results for plant relationship competition found that kin plants had a significantly greater number of lateral roots and a significantly longer primary root. The last chapter, Chapter 5, includes a summary of our conclusions. Our study found SSS occurring in the Sand Lake Estuary in Oregon with female-majority sites higher in phosphorus and root colonization higher in percent colonization of arbuscular mycorrhizal fungi compared to male-majority sites. Based on the sexual specialization hypothesis as a mechanism for SSS, we found that females had greater fitness in female-majority sites compared to male-majority sites, suggesting that sexual specialization is occurring in reproductive females. We then tested the niche partitioning hypothesis for SSS, and we found consistent lab and field results suggesting that niche partitioning due to inter-sexual competition is an explanation for why females and males D. spicata plants spatially segregate themselves at the juvenile life history stage. Furthermore, we found that plants that have the same mother had a significantly greater number of lateral roots and a significantly longer primary root. These results suggest that KIN plants respond differently to one another compared to plants paired with a plant not from the same mother (STRANGER) or when the plant is alone (OWN).

Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS) is a genetic disorder that results from triplication of human chromosome 21 (Hsa21) and occurs in around 1 in 1000 live births. All individuals with DS present with skeletal abnormalities typified by craniofacial features, short stature and low bone mineral density (BMD). Differences between males and females with DS suggest a sexual dimorphism in how trisomy affects skeletal deficits associated with trisomy 21 (Ts21). Previous investigations of skeletal abnormalities in DS have varied methodology, sample sizes and ages making the underlying causes of deficits uncertain. Mouse models of DS were used to characterize skeletal abnormalities, but the genetic and developmental origin remain unidentified. Over-expression Dyrk1a, found on Hsa21 and mouse chromosome 16 (Mmu16) has been linked to cognitive deficits and skeletal deficiencies. Dp1Tyb mice contain three copies of all of the genes on Mmu16 that are homologous to Hsa21, males and females are fertile, and therefore are an excellent model to test the hypothesis that gene dosage influences the sexual dimorphism of bone abnormalities in DS. Dp1Tyb at 6 weeks 16 weeks showed distinctive abnormalities in BMD, trabecular architecture, and reduced bone strength over time that occur generally through an interaction between sex and genotype. Increased gene dosage and sexual dimorphism in Dp1Tyb mice revealed distinct phenotypes in bone formation and resorption. To assess how Dyrk1a influences the activity and function of osteoblasts Ts65Dn female trisomic mice, female mice with a floxed Dyrk1a gene (Ts65Dn, Dyrk1afl/+) were be bred to Osx1-GFP::Cre+ mice to generate Ts65Dn animals with a reduced copy of Dyrk1a in mature osteoblast cells. Female Ts65Dn,Dyrk1a+/+/+ and Ts65Dn,Dyrk1a+/+/-displayed significant defects in both trabecular architecture and cortical geometry. Ultimate force was reduced in trisomic animals, suggesting whole bone and tissue level properties are not adversely affected by trisomy. Reduction of Dyrk1a functional copy number in female mice did not improve skeletal deficits in an otherwise trisomic animal. Dyrk1a may not alter osteoblast cellular activity in an autonomous manner in trisomic female mice. These data establish sex, gene dosage, skeletal site and age as important factors in skeletal development of the skeleton in DS mice, potentially paving the way for identification of the causal dosage-sensitive genes in both male and female animals.

Sexual dimorphism is the phenotypic difference between males and females of the same species, but how these phenotypic differences arise is largely unstudied at the molecular level. It is understood that sexual selection, or competition for mates, drives sexual dimorphism, but more recently it has been suggested that resource partitioning, or niche pressure, may exert evolutionary pressure, leading to sexual dimorphism. Many members of the sarseilloid family of ostracods exhibit sexual dimorphism of their lateral eyes with males having an image forming eye, while females have a rudimentary eye limited to sensing light and dark. Ostracods progress through five instar stages of development before becoming an adult, and by studying expression levels of selected developmental genes at instar IV, V adult stages and embryos, the underlying expression pattern change that leads to phenotypic differences can be seen. By comparing the differences in expression between two sarseilloid species, Euphilomedes carcharodonta and Euphilomedes morini , we can see how these species develop their specific phenotypes. In E. carcharodonta and E. morini , the genes Sine oculis, Dachshund, Seven in absentia, Chaoptic, Protein Kinase C and Opsin show different expression patterns between groups. The highest expression levels of Sine oculis are in developing embryos when compared to other stages of development. Dachshund, Seven in absentia, Chaoptic, Protein Kinase C and Opsin show significantly different patterns in males or noticeable male trends, demonstrating that these genes are important in the development and function of the sexually dimorphic lateral eye. E. carcharodonta and E. morini show similar gene expression patterns suggesting that these patterns have been conserved over evolutionary time to produce the observed dimorphic morphology.

The genetics of switchback evolution is largely unknown. While it is assumed that latent gene regulatory networks become reactivated to recreate an ancestral tissue, the details regarding this reactivation has yet to be elucidated. How has a network been maintained over the evolutionary history of this group? Are certain genes within these pathways more susceptible to suppression than other genes? In this study, I examined Euphilomedes carcharodonta, a member of the Sarsielloidea superfamily of ostracods, a clade which has demonstrated the loss and regain of the lateral eye multiple times over its evolutionary history. In particular, I looked at the genetic mechanisms for the development of the sexually dimorphic lateral eye, in which males have large, multifaceted image-forming eyes typical to those of other pancrustaceans (Hexapoda+Crustacea) while females do not. This sexual dimorphism is of particular interest because it allows me to study the genetic underpinnings of a regained trait using individuals of near-identical genetic backgrounds, as these organisms have a singlechromosome sex determination system (XXIXO). Examination of developmental eye genes ec-Dachshund, ec-Daughtless, ecChaoptic, ec-Shaven, and ec-Epidermal growth factor receptor showed differential gene expression patterns in which juvenile male eyes expressed these genes at a higher level than did juvenile female eyes. These genes are thus candidate genetic components of 6 switchback evolution, as this data is a first step towards comparative transcriptomics and gene expression studies comparing multiple species.