Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 174-194). Also available online.

Thesis (Ph. D.)--Case Western Reserve University, 2009. / [School of Medicine] Department of Physiology and Biophysics. Includes bibliographical references.

Thesis (Ph. D.)--Rutgers University, 2009. / "Graduate Program in Ecology and Evolution." Includes bibliographical references (p. 148-163).

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 174-194). Also available in print.

Parasite population dynamics and the evolution of life history characteristics are strongly correlated with the processes of host infection, survival within a host and reproduction, with each process posing a challenge to the parasitic lifestyle. Macroparasites living in marine environments have evolved extreme changes in physiology, morphology and life history traits to overcome these challenges. This study focused on the infective and reproductive stage of the parasitic isopod, Cymothoa excisa, a common parasite on Atlantic croaker, (Micropogonias undulatus), along the Texas coast. A two year survey identified infection rates and the relationship between fish density and size and parasite load, size and fecundity. Isopod morphology was quantified for each life stage, identifying shape transitions through ontogeny and sex change. Sex change in C. excisa was found to be driven by the absence of conspecific parasites within a host, where sex change only occurred in the first individual to arrive. To understand the infective stage of C. excisa parasite energetics and host detection mechanisms were tested. Parasites with free-living life stages have a narrow window to infect a host and have evolved a number of mechanisms to detect and locate a host. I used a series of energetic experiments to determine an infection window for free-swimming larvae (mancae) and behavioral response experiments testing both visual and chemical cues associated with host detection. Mancae were found to have a narrow infection window, where mancae began searching for a host as soon as they are born, but quickly switch to an ambush strategy to conserve energy. Mancae were also found to be responsive to both visual and chemical cues from its common fish host, as well as a non-host fish, indicating that chemical cues are used in host detection, but chemical specificity is not a mechanism that C. excisa uses to find its common host. The results from this study have implications to parasitic species and their hosts, as well as to other areas of study, including population and ecosystem dynamics. / text

published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

To study the pathogenesis and preventive strategies of acute and chronic graft-versus-host disease (aGVHD, cGVHD) after hematopoietic stem cell transplantation (HSCT), murine models of aGVHD and cGVHD were constructed. In addition, the role of CD4+CD25+ regulatory T cells (Tregs) in GVHD was also investigated in these models. My project consisted of three parts, including MHCI,II mismatched (part 1) and haploidentical BMT(part2) based aGVHD, and MHC matched, minor histocompatibility antigen (miHA)mismatched cGVHD(part 3). In the first model, aGVHD resulting from an MHC I, II mismatched aGVHD (B6(H-2b)→BALB/c(H-2d)) HSCT was studied, particularly with respect to the role that CD4+CD25+Tregs played. The results showed that CD4+CD25-T-cells induced more severe aGVHD than CD4+ T-cells, resulting in more extensive target organ lesions, especially in colon. The possible mechanism might be due to the enhanced proliferation and differentiation towards pathogenic Th1 cells. In the second model, haploidentical (B6(H-2b)→[C57BL/6×CBA/Ca]F1(H-2b×k)) HSCT was used to studied the role of CD4+or CD8+T-cells in aGVHD.Both high dose of donor CD4+-and CD8+-T-cells have the ability to induce lethal aGVHD in the hosts. However, the clinical and histological features of aGVHD induced by CD4+T-cells were significantly different from that induced by CD8+T-cells. Both donor CD4+-and CD8+-T-cells showed marked proliferation and differentiation towards CD4+IFN-γ+Th1and CD8+IFN-γ+cells, respectively. Polyclonalexpanded freshly isolatednTregs (exp-nTregs) showed obvious proliferation, increased apoptosis, and rapid loss of Foxp3 expression with impaired suppressive function. Exp-nTregs were further investigatedfor their preventive function in aGVHD in this haploidentical HSCT model. The results showed that exp-nTregs were capable of attenuating either CD4+-or CD8+-T-cell-induced aGVHD with significantly prolonged survival rate. In the third model, cGVHD was investigatedin DBA/2 (H-2d)→BALB/c (H-2d) HSCT, where the biologic readout was proteinuria and skin fibrosis. The results showed that donor CD4+T-and B220+B-cells were the main effectors in the pathogenesis of cGVHD. Notably, a more active germinal center (GC) reaction existed in the cGVHD cohorts compared with the control syngeneic cohort. Furthermore, Tfh and GC B-cells were shown to have originated from donor CD4+T-and B220+B-cells, respectively. Importantly, Tfh and GC B cells were mutually stimulatory and inter-dependent. In conclusion, three murine models were used to investigate aGVHD and cGVHD. The results showed that Tregs played a significant suppressive role in aGVHD complicating haploidentical HSCT. Furthermore, a hyperactive germinal center reaction might be the main cause of cGVHD. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

abstract / Dentistry / Doctoral / Doctor of Philosophy

Gamma-ray bursts (GRBs) are relativistic explosions which originate at cosmological distances, and are among the most luminous transients in the universe. Following the prompt gamma-ray emission, a fading synchrotron "afterglow" is detectable at lower energies. While long-duration GRBs (duration > 2 sec) are linked to the deaths of massive stars, the progenitors of short-duration GRBs (duration < 2 sec) have remained elusive. Theoretical predictions formulated over the past two decades have suggested that they are the mergers of two compact objects, involving either two neutron stars (NS-NS) or a neutron star and a black hole (NS-BH). Such merging systems are also important to understand because they are premier candidates for gravitational wave detections with upcoming facilities and are considered likely sites of heavy element nucleosynthesis. The launch of the Swift satellite in 2004, with its rapid multi-wavelength monitoring and localization capabilities, led to the first discoveries of short GRB afterglows and therefore robust associations to host galaxies. At a Swift detection rate of ~8 events per year, the growing number of well-localized short GRBs enables comprehensive population studies of their afterglows and environments for the first time. In this thesis, I undertake a multi-wavelength observational campaign to address testable predictions for the progenitors of short GRBs. From their local environments, I show that short GRBs explode in diffuse regions of their host galaxies and are weakly correlated with the distribution of stellar mass and star formation in their host galaxies. I study the host galaxy demographics for the entire population and find that ~20-40% of short GRBs originate from elliptical galaxies, implying an older stellar progenitor. From their afterglows, I present evidence that some short GRBs are collimated in narrow jets of ~5-10 degrees, directly affecting the true energy scale and event rate. Finally, taking advantage of a decade of broad-band afterglow observations at radio through X-ray wavelengths, I find that short GRBs have median isotropic-equivalent energies of ~10^51 erg and that their local environments have low densities, ~10^-3-10^-2 cm^-3. Taken together, this thesis comprises several lines of independent evidence to demonstrate that short GRBs originate from the mergers of two compact objects, and also provides the first constraints on the explosion properties for a large sample of events. With the direct detection of gravitational waves from compact object mergers on the horizon, these studies provide necessary inputs to inform the next decade of joint electromagnetic-gravitational wave search strategies. / Astronomy

No description available.