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Using TIRF microscopy to analyze stimulated and basal state B-cell MHC II clustering in response to ageing and dietary fish oil
(East Carolina University, 2013)
This research focused on developing an efficient TIRF microscopy approach to evaluate membrane protein organization. More specifically, the data demonstrate that TIRF microscopy can detect changes in ex vivo B-cell MHC II ...
The unique roles of IFE-1, a germline-specific isoform of eukaryotic translation factor 4E, during gametogenesis
(East Carolina University, 2009)
Fertility and embryonic viability are measures of efficient germ cell growth and differentiation. During oogenesis, spermatogenesis and embryogenesis cells initially proliferate then differentiate into specific tissues. New proteins are required for both cell growth and differentiation, requiring qualitative and quantitative changes in protein synthesis. During late gametogenesis and early embryogenesis the expression of the appropriate proteins is a primarily due to translational control. Translational control of mRNAs is mediated in part by eukaryotic initiation factor 4E (eIF4E). eIF4E binds the methylated 5' cap of mRNA and recruits it to the ribosome. The nematode worm C.elegans expresses five isoforms of eIF4E (termed IFE-1 through 5). IFE-1 is expressed primarily in the germline and is the only isoform that associates with P granules by binding directly to PGL-1. P granules are ribonucleoprotein particles (RNPs) that contain stored mRNAs and proteins needed for oogenesis and early embryogenesis. Using a strain that lacks IFE-1, I assessed the translational efficiency of maternal mRNAs bound and not bound to P granules by polysome fractionation. Translation of pos-1, pal-1, mex-1, oma-1, ced-4 and glp-1 mRNAs was inefficient in the ife-1 strain relative to wild type worms. GAPDH (gpd-3) mRNA translation was not affected. We also observed differences in the pattern of expression of the MEX-1 protein during oogenesis. In males, secondary spermatocytes failed to complete cytokinesis at 25°C in absence of IFE-1. Males deficient of IFE-1 therefore lacked mature sperm. In addition, ife-1 spermatocytes prematurely accumulated pro-apoptotic CED-4, homolog to mammalian Apaf-1, during spermatogenesis. In ife-1 worms fertility was decreased by 80% due to decreased viability of both oocytes and spermatocytes. Our data indicate two unique roles for eIF4E (IFE-1 isoform) in late oogenesis and spermatogenesis. We suggest that IFE-1 preferentially recruits regulated mRNAs at critical times during germ cell development. ...
The involvement of cap-independent mRNA translation in cell fate decisions
(East Carolina University, 2014)
During cell stress many biochemical processes are shut down. For
example, global mRNA translation initiation is inhibited due to the
disruption of the cap-dependent mRNA recruitment mechanism. One
specific example of ...
N-3 polyunsaturated fatty acids differentially enhance B-cell mediated immunity in lean and obese mice
(East Carolina University, 2014)
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are
bioactive n-3 polyunsaturated fatty acids (PUFAs) in fish oil that
exert immunomodulatory effects. The general paradigm suggests n-3
PUFAs exert immunosuppressive ...
Multiple Translation Factor eIF4G (IFG-1) Isoforms are Required for the Apoptosome-Dependent Activation of Germ Cell Apoptosis
(East Carolina University, 2010)
Apoptosis is a naturally occurring process during animal development required for the programmed killing and removal of injured cells. Cellular insult induces a switch in translation that allows for the rapid synthesis ...
Post-Transcriptional Regulation of mRNA Metabolism during Differentiation of 3T3-L1 Cells: Role of HuR
(East Carolina University, 2010)
Our studies address early control points in the differentiation process that are necessary for expression as well as the maintenance of the adipocyte phenotype. We have focused on the post-transcriptional regulation of ...
The Distribution Of Regulated Actomyosin States Is Central To Cardiac Muscle Regulation And Disturbance Of This Distribution Leads To Congenital Cardiomyopathies
(East Carolina University, 2009)
Hypertrophic and restrictive cardiomyopathies are congenital cardiac diseases that have an incidence of over one in five hundred and may lead to sudden cardiac death. One of the main impediments to directed treatment is ...
Discovery and investigation of a novel role for mitochondrial prohibitin in mitigating acute heart failure in endotoxic shock
(East Carolina University, 2014)
Sepsis results in more than 200,000 deaths annually and is the 10th leading cause of death in the United States (US). In spite of significant advances in medical care the mortality rate for sepsis has continued to rise. ...
The therapeutic potential of Rho GTPase intervention
(East Carolina University, 2013)
Small GTPases of the Rho family are well established regulators of critical cellular functions including cytoskeletal remodeling, motility, vesicle trafficking and cell cycle control. Additionally, aberrant signaling ...
Fesselin and caldesmon: natively unfolded proteins in smooth muscle regulation
(East Carolina University, 2010)
Dysregulation of smooth muscle contraction is linked to diseases such as atherosclerosis, asthma, hypertension, urinary incontinence, premature birth and others. The goal of this project is to contribute to our understanding ...