Thesis advisor: David R. Burgess / Microtubule (MT) asters are radial arrays of MTs nucleated from a microtubule organizingcenter (MTOC) such as the centrosome. Within many cell types, which display highly diverse size and shape, MT asters orchestrate spatial positioning of organelles to ensure proper cellular function throughout the cell cycle and development. Therefore, asters have adopted a wide variety of sizes and morphologies, which are directly affects how they migrate and position within the cell. In large cells, for example during embryonic development, asters growth to sizes on the scales of hundreds of microns to millimeters. Due to this relatively enormous size scale, it is widely accepted that MT asters migrate primarily through pulling mechanisms driven by dynein located in the cytoplasm and/or the cell cortex. Moreover, prior to this dissertation, significant contributions from pushing forces as a result of aster growth and expansion against the cell cortex have not been detected in large cells. Here we have reinvestigated sperm aster growth, morphology, and positioning of MT asters using the large interphase sperm aster of the sea urchin zygote, which is historically a powerful system due to long range migration of the sperm aster to the geometric cell center following fertilization. First, through live-cell quantification of sperm aster growth and geometry, chemical manipulation of aster geometry, inhibition of dynein, and targeted chemical ablation, we show that the sperm aster migrates to the zygote center predominantly through a pushing-based mechanism that appears to largely independent of proposed pulling models. Second, we investigate the fundamental principles for how sperm aster size is determined during growth and centration. By physically manipulating egg size, we obtain samples of eggs displaying a wide range of diameters, all of which are at identical developmental stages. Using live-cell and fluorescence microscopy, we find strong preliminary evidence that aster diameter and migration rates show a direct, linear scaling to cell diameter. Finally, we hypothesize that a collective growth model for aster growth, or centrosome independent MT nucleation, may explain how the sperm aster of large sea urchin zygotes overcomes the proposed physical limitations of a pushing mechanism during large aster positioning. By applying two methods of super resolution microscopy, we find support for this collective growth model in the form of MT branching. Together, we present a model in which growth of astral MTs, potentially through a collective growth model, pushes the sperm aster to the zygote center. / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

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This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

In this Thesis we present a description of α cluster nuclei, in particular focusing on the case of 9 Be, with αn and αα interactions derived from Cluster Effective Field Theory (EFT). The two-body potentials are regularized by a Gaussian cutoff which cures the short-distance dependence of the interaction and the potential parameters are found comparing the effective range expansion (ERE) with the calculated T-matrix. The calculation of the ground-state energies is carried out by diagonalizing the Hamiltonian on a Non symmetryzed Hyperspherical Harmonics basis in momentum space. Using only two body interactions a rather strong cutoff dependence appears. However, we are able to reproduce the experimental ground-state energies for selected cutoff values for most of the studied nuclei. The strong cutoff dependence indicates the lack of three-body forces, therefore we extend our Cluster EFT approach by including such many-body forces. Finally, the 9Be photoabsorption cross-section is studied via the Lorentz integral transform method (LIT), focusing on the low-energy resonances coming from the electric dipole transitions. By fine tuning the parameters of the three-body force, we are able to reproduce, up to 4 MeV, the considered experimental resonances. For the description of the spectrum at higher energies the inclusion of the αα D-wave potential seems to be necessary.

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<p> The prevailing theory of Migdal for predicting the excitation probabilities of an atom from α-decay of the nucleus, considers the α-particle, after it has been emitted by the nucleus, as following a classical trajectory and interacting with the atom quantum mechanically. Recently an attempt was made to properly model this quantum mechanical phenomenon, in one dimension, with a quantum wavefunction treatment of the decaying α-particle, but a discrepancy was found between the new predictions and that of the traditional method. In light of this discrepancy, we have studied the various approximations made in that work. Our results concur with recent follow up work suggesting that agreement should be found between a fully quantum mechanical model and with the classical model of α-particle propagation where the α-particle is treated as a point particle.</p> / Thesis / Master of Science (MSc)

<p> The present thesis examined the relative contribution of hypothalamic and nucleus accumbens dopaminergic activity to the control of sucrose sham feeding. Bilateral intracranial infusions of the dopamine antagonist, haloperidol at doses of 1.25, 2.5, 5 and 7.5 ug, into the hypothalamus and nucleus accumbens produced dose-dependent suppressions of sham feeding of a 15% sucrose solution. No differences in temporal pattern of intake were observed between hypothalamic and nucleus accumbens infusions under drug or vehicle conditions. Also, motor deficits were observed with the highest dose of haloperidol (7.5 ug) while the three lower doses inhibited sham feeding without obvious signs of motor impairment. These results suggest that mesolimbic as well as hypothalamic dopaminergic activity mediate the hedonic aspects of feeding. </p> / Thesis / Master of Science (MSc)

Retinogeniculate (RG) synapses connect retinal ganglion cells to the thalamic relay cells of the dorsal lateral geniculate nucleus (dLGN). They are critical for regulating the flow of visual information from retina to primary visual cortex (V1). RG synapses in dLGN are uniquely larger and stronger than their counterparts in other retinorecipient regions. Moreover, in dLGN, RG synapses can be classified into two groups: simple RG synapses, which contain glia-encapsulated single RTs synapsing onto relay cell dendrites, and complex RG synapses, which contain numerous RTs that converge onto the shared regions of relay cell dendrites. To identify target-derived molecules that direct the transformation of RTs into unique RG synapses in dLGN, I used RNAseq to obtain the whole transcriptome of dLGN and its adjacent retinorecipient nucleus, vLGN, at different time points during RG synapses development. Leucine-Rich Repeat Transmembrane Neuronal 1 (LRRTM1), a synaptogenic adhesion molecule, was the candidate I selected based on its expression pattern. Here, I discovered that LRRTM1 regulates the development of complex RG synapses. Mice lacking LRRTM1 (lrrtm1-/-) not only show a significant reduction in the number of complex RG synapses but they exhibit abnormal visual behaviors. This work reveals, for the first time, a high level of retinal convergence onto dLGN relay cells in thalamus and the functional significance of this convergence for vision. / Ph. D.