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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Pop2: A Potential Regulator of Hmt1-Catalyzed Arginine Methylation in Yeast

Excell, Celeste 01 May 2014 (has links)
Protein arginine methylation is an important post-translational modification that is vital in regulating various cellular processes such as gene transcription, cell signaling, and RNA processing. Protein arginine methyltransferases (PRMTs) are responsible for performing this important modification. PRMT1 (protein arginine methyltransferase 1) and Hmt1 (hnRNP methyltransferase 1) are the predominant PRMTs in humans and yeast, respectively. Despite growing momentum in this field, relatively little is understood about PRMT regulation. Further work discovering how PRMTs are regulated will greatly advance our understanding of diseases where PRMTs have been implicated, such as heart disease, viral pathogenesis, and cancer. It has been discovered that a human protein called hCaf1 (human Ccr4-associated factor 1) is a regulator of PRMT1 with respect to certain substrates, and also colocalizes with PRMT1. We present data that suggest the yeast homolog of hCaf1, Pop2, may also perform a similar function on Hmt1. We provide data on the expression and purification of a truncation of Pop2 from S. cerevisiae, including the temperature sensitivity of one construct of Pop2 and its susceptibility to precipitation. We also demonstrated concentration-dependent inhibition of Hmt1-catalyzed methylation of histone H4 by Pop2 in vitro. Yeast cell lysates also showed altered patterns of methylation in the presence and absence of Pop2 in vivo. In an effort to understand the mechanism employed by Pop2 to accomplish this regulatory function, pull-downs were performed suggesting that Pop2 directly interacts with histone H4, a substrate of Hmt1. Mutagenic studies with Pop2 suggested a region that may be responsible for this interaction. Given these data, we hypothesized that Pop2 is able to inhibit the methylation of histone H4 via a substrate-sequestering mechanism. Further experimentation will determine the precise interaction surfaces of Pop2 and substrate, and continue to define the details of methylation inhibition by Pop2, including the scope of its influence in the cell.
2

Understanding the Long-Term Change of the Atlantic Meridional Overturning Circulation (AMOC) during the Late Twentieth Century

Kim, Who Myung 03 October 2013 (has links)
The strength of the Atlantic meridional overturning circulation (AMOC) is believed to be associated with changes in surface buoyancy in the subpolar North Atlantic, which naturally leads to a notion that the AMOC has been weakening under global warming. Yet, a variety source of observations and its assimilation into ocean circulation models have not supported such an AMOC decline so far. In this study, an aspect that has not been paid attention, regarding the maintenance of the AMOC strength, is explored: storm activity in the subpolar North Atlantic (NA). An analysis using reanalysis data shows that the wintertime turbulent heat flux variability in the LS deep convection region is largely controlled by a small number of extreme heat flux event days, suggesting a pivotal role of winter storms in prompting LS deep-water formation. A set of forced ocean-ice model simulations, in which synoptic winter storm activity associated with these event days is either suppressed or doubled over the subpolar NA, confirms the above analysis as the altered storm activity results in a substantial change in LS convection and the AMOC strength. These experiments also show an upward AMOC trend during the late twentieth century, the degree of which is to some extent related to the intensity of storm activity in the LS. The upward AMOC trend found in the first part of the dissertation opposes to a downward AMOC trend in the twentieth century coupled model simulations employing the identical ocean component. An analysis suggests that contrast to the ocean-ice model, storm activity in the LS convection region and associated heat flux decreases during the late twentieth century. Although there is also a buoyancy increase over the LS, the wintertime heat flux decrease appears to be a more dominant factor for a decrease in convection in the LS, as an increasing freshwater input from Arctic/Subarctic Ocean bypasses the interior LS along the western boundary current. Therefore, the downward AMOC trend in the coupled model can be linked ultimately to the decreasing storm activity over the LS. This study therefore suggests that storm activity over the major convection regions needs to be paid further attention in assessing AMOC variations, including long-term trend in response to a warming scenario, in future studies.

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