<p> Agents are of central importance to cognitive science, but research usually takes them as pre-given and proceeds to study some of their particular aspects, often without awareness of or a definite answer to the question, &ldquo;what is an agent?&rdquo; The conceptual framework of autopoiesis and enaction provides a foundation that defines agents as emergent individuals that act in an environment to fulfill their physiological needs. </p><p> To establish this definition in concrete examples, this dissertation introduces computational models and analyses that demonstrate several properties of agents. It examines an artificial chemistry that supports the emergence of minimal protocells. These protocells have a metabolism made of autocatalytic components, and an external boundary that self-assembles and encapsulates the metabolism, keeping it from diffusing into the environment. Metabolism and boundary are mutually enabling processes, which together counter the effects of diffusion and decay. When their symbiosis is broken, the protocell disintegrates. </p><p> Systematic analysis reveals the rich consequences of protocellular organizations. Ontogenies are mapped as network structures, with the networks' nodes as reachable protocell morphologies and its edges as the transitions between morphologies. Analyses of these networks reveal properties such as irreversibility (some changes cannot be reversed under any circumstance) and branching (unfolding down one ontogeny excludes morphologies accessible by other ontogeny). Viability is quantified as expected lifespan, and measured across different protocell configurations. This provides a basis for measuring agents' basic goal of adaptivity &mdash; to increase their viability in a given environment through internal restructuring or environmental change. </p><p> The cellular Potts model (CPM) framework is examined to study structural coupling (the bi-directional interactions between an agent and environment). The network-based methodology for analyzing ontogenies is extended to incorporate a local environmental state and is demonstrated in a CPM. This reveals several interesting features, such as a divergence in the space of possible ontogenies when placed in different environments, and that niche construction can increase an individual's viability.</p>

<p>The basement membrane (BM) is a highly conserved form of extracellular matrix that underlies or surrounds and supports most animal tissues. BMs are crossed by cells during various remodeling events in development, immune surveillance, or during cancer metastasis. Because BMs are dense and not easily penetrable, most of these cells must open a gap in order to facilitate their migration. The mechanisms by which cells execute these changes are poorly understood. A developmental event that requires the opening of a BM gap is C. elegans uterine-vulval connection. The anchor cell (AC), a specialized uterine cell, creates a de novo BM gap. Subsequent widening of the BM gap involves the underlying vulval precursor cells (VPCs) and the π cells, uterine neighbors of the AC through non-proteolytic BM sliding. Using forward and reverse genetic screening, transcriptome profiling, and live-cell imaging, I investigated how the cells in these tissues accomplish BM gap formation. In Chapter 2, I identify two potentially novel regulators of BM breaching, isolated through a large-scale forward genetic screen and characterize the invasion defect in these mutants. In Chapter 3, I describe single-cell transcriptome sequencing of the invasive AC. In Chapter 4, I describe the role of the π cells in opening the nascent BM gap. A complete developmental pathway for this process has been elucidated: the AC induces the π fate through Notch signaling, after which the π cells upregulate the Sec14 family protein CTG-1, which in turn restricts the trafficking of DGN-1 (dystroglycan), a laminin receptor, allowing the BM to slide. Chapter 5 outlines the implications of these discoveries.</p> / Dissertation

<p> The uterus is essential for mammalian reproduction as it provides environment for conceptus implantation and subsequent development. Endometrial glands synthesize and secrete or transport substances critical for conceptus survival and implantation, demonstrated by the fact that female sheep and mice containing no uterine glands are infertile mainly due to impaired implantation and early pregnancy loss. FOXA2, a transcription factor, has been showed indispensable for not only the development of uterine glands in the neonate but also its differentiated function in the adult. The goal of the current study is to (1) generate a mouse model for the conditional overexpression of FOXA2, and to (2) determine the effects of FOXA2 overexpression on uterine morphogenesis and female fertility.</p><p> In this thesis, Chapter 1 will review the early pregnancy of mice and discuss in detail how the early pregnancy events including blastocyst activation, uterine receptivity, apposition, attachment, penetration, stromal cell decidualization are regulated by different factors and signaling pathways. Chapter 1 will also introduce FOXA2 including its finding, structure, functions in organ development and differentiated function, functions in carcinogenesis and the regulation of its expression. Chapter 2, the research chapter, shows that we developed a mouse model which could express FOXA2 continuously only in the cells with expression of Cre recombinase. By applying two different mouse strains with special Cre expression, we found that misexpression of FOXA2 in the neonatal mouse uterus alters or inhibits normal differentiation and genesis of endometrial glands and function of the adult uterus, leading to female infertility. It also suggests that regulatory elements may localize inside the <i>Foxa2</i> coding sequence and can be targeted by some unknown epigenetic mechanism. This chapter has been recently published in a journal: Endocrinology.</p><p>

No description available.

No description available.

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Cell and Developmental Biology." Includes bibliographical references (p. 77-86).

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Cell and Developmental Biology." Includes bibliographical references (p. 90-94).

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<p> Leaf senescence is the final stage of leaf development that results in the highly ordered degeneration of cellular organelles and reallocation of nutrients to younger developing tissue. These cellular changes are accompanied by global changes in gene expression. Epigenetic modifications, such as DNA methylation, changes in histone variants, and covalent modification of histones have been shown to influence the expression of genes. Previous ChIP-seq and RNA-seq analyses revealed a correlation between the trimethylation of histone H3 lysine 4 (H3K4me3), a mark associated with active transcription, and the expression of a subset of senescence associated genes (SAGs) during leaf senescence in <i>Arabidopsis thaliana</i>. In this study, T-DNA insertion mutants of five histone methyltransferases (HMTases or ATX/ATXR) and five histone demethylases (HDMases or KDM5b) were examined to determine whether the expression of targeted SAGs was affected. In addition, total chlorophyll and protein levels, as well as plant development were investigated to determine whether these mutants function in regulating plant development and catabolism during senescence. The results show that while the expression of target SAGs were not affected by the mutants, other processes were affected. <i> atx4</i> was observed to have higher levels of chlorophyll and protein, which indicates ATX4 may function in positively regulating catabolism during leaf senescence. Additionally, <i>kdm5b_1</i> was observed to have larger seeds, which indicates <i>KDM5b_1</i> may function to restrict seed size in <i>Arabidopsis</i>.</p>

<p> Many neurological diseases associated with cortical and hippocampal dysfunctions are sexually dimorphic in incidence and have been linked to defects in mRNA splicing. My thesis investigated the sex- and age-related changes in gene expression of six RNA processing genes within the cortex/hippocampus of male and female mice during early development. Gene expression was measured using RT-qPCR with mouse cortex/hippocampus samples collected on the day of birth and one week after birth. Immunoblotting was also used to measure the protein levels of one RNA processing gene to determine whether the expression paralleled mRNA expression. <i>Dhx8 mRNA</i> and <i>Sf3a2 </i> protein expression was found to be sexually dimorphic, while <i> Thoc3, Tut1,</i> and <i>Sf3a2</i> showed mRNA expression changes with age. Sexually dimorphic and age-related expression of these genes suggests that RNA processing may play an important role in brain sexual differentiation and early neural development; however the underlying mechanisms remain to be elucidated.</p>