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- 5-methylcytosine, Activation induced deaminase, APOBEC3A, APOBEC3G, cytosine deamination, DNA demethylation (1)
- 6-substituted pyrrolo[2,3-d]pyrimidine antifolates, acidic tumor microenvironment, antifolates, Proton-coupled folate transporter, solid tumor targeting (1)
- ALDH5A1, Breast, Ductal Carcinoma in situ, microarray, RNA Sequencing (1)
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- BrdU, Gender, Oligodendrocyte Progenitor, Proliferation, Subventricular zone (1)
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Articles 1 - 30 of 46
Full-Text Articles in Life Sciences
"Fine-Tuning" Of Ribosomal Structure And Functions By Pseudouridylation And Rna-Protein Interactions, Jun Jiang
"Fine-Tuning" Of Ribosomal Structure And Functions By Pseudouridylation And Rna-Protein Interactions, Jun Jiang
Wayne State University Dissertations
ABSTRACT
"Fine-tuning" of ribosomal structure and functions by pseudouridylation and RNA-protein interactions
by
JUN JIANG
AUGUST 2012
Advisor: Prof. John SantaLucia Jr.
Major: Chemistry (Biochemistry)
Degree: Doctor of Philosophy
Ribosomal structure and functions appear to be "fine-tuned" by pseudouridylation and RNA-protein interactions. Pseudouridylation may promote base stacking interactions by mediating the base stacking between residues on both sides. In the RNA duplex region, this enhanced stacking interaction contributes to stabilization of duplex folding. In the loop region, enhanced stacking in one structural motif may destabilize the conformation of adjacent structural residues. This hypothesis is supported by both UV-melting experiments, where …
The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin
The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin
Wayne State University Dissertations
Folates are essential cofactors of tumor cell proliferation and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack of tumor selectivity. Facilitative transport of folates into mammalian cells is achieved by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). As PCFT is a folate-proton symporter with an acidic pH optimum, PCFT may provide a mechanism for targeting cytotoxic antifolates to tumors, based on their acidic microenvironments. To establish the …
Cationic Amphiphilic Drug-Induced Autophagosome Accumulation Is Due To Autophagosome Sequestration Within Vimentin Intermediate Filament Networks Resulting In Prolonged Autophagosome Half-Life, Miriam Devorah Kleinman
Cationic Amphiphilic Drug-Induced Autophagosome Accumulation Is Due To Autophagosome Sequestration Within Vimentin Intermediate Filament Networks Resulting In Prolonged Autophagosome Half-Life, Miriam Devorah Kleinman
Wayne State University Dissertations
Accumulations of autophagosomes and non-esterified cholesterol are
observed in several cell lines derived from lysosomal storage diseases,
including Niemann Pick Type C (NPC). The relationship between
autophagosome accumulation and lysosomal non-esterified cholesterol is
unclear. Exposure of murine hepatoma 1c1c7 cultures to the cationic
amphiphilic drugs (CADs) U18666A, imipramine and clozapine caused
lysosomal non-esterified cholesterol and autophagosome accumulation.
Measurement of LC3-II conversion in the presence of lysosomal inhibitors
bafilomycin A1 and NH4Cl, degradation of long-lived proteins, and
colocalization of GFP-LC3 and LAMP1 indicated an increase in
autophagosome synthesis without compensatory increase in clearance.
Autophagosome synthesis was blocked using 3-MA to monitor …
The Structural Requirements Of Histone Deacetylase (Hdac) Inhibitors: Suberoylanilide Hydroxamic Acid (Saha) Analogues Modified At C3, C6, And C7 Positions Enhance Selectivity, Sun Ea Choi
Wayne State University Dissertations
Histone deacetylase (HDAC) proteins are targets for drug design towards the treatment of cancers since overexpression of HDAC is linked to cancer. Several HDAC inhibitors, including the FDA approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat), have cleared clinical trials and emerged as anti-cancer drugs. However, SAHA inhibits all of the 11 metal ion-dependent HDAC proteins. Therefore, we synthesized several libraries of small molecule HDAC inhibitors based on SAHA to help understand the structural requirements of inhibitory potency and isoform selectivity.
In previous work, SAHA analogues functionalized at the C2 position (C2-SAHA analogues) near the metal binding hydroxamic acid displayed decreased …
Development Of A Cargo Delivery System And Inhibition Studies Focused On Clostridium Difficile Toxin A, Stephanie Marie Kern
Development Of A Cargo Delivery System And Inhibition Studies Focused On Clostridium Difficile Toxin A, Stephanie Marie Kern
Wayne State University Dissertations
Virulence factors of pathogenic bacteria are to be blamed for life-threatening infections such as diphtheria, anthrax, botulism, and tentanus. In the case of enzymatic exotoxins, disease arises from cytotoxic proteins, and cytotoxicity is acheived only after cell entry. This intrinsic mechanism for cell entry is intriguing from research and medical views. Along with a review on existing cargo delivery systems utilizing protein toxins and the usefulness of such a system, here is described the first reported Clostridium difficile toxin A fusion protein, luciferase-TcdA, and evidence of the successful transport of an active enzyme, luciferase, into the cytosol of vero cells. …
Drug Resistance Mechanisms And Drug Design Strategies For Human Immunodeficiency Virus And Hepatitis C Virus Proteases, Yong Wang
Wayne State University Dissertations
The antiviral drug development has improved steadily to treat the infections of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) which represent heavy public health burdens. The viral protease plays an indispensable role in viral maturation and therefore becomes one of the most important targets for drug design. Nine HIV-1 protease inhibitors and two HCV protease inhibitors have been developed and approved by the U.S. Food and Drug Administration. However, mutations in the protease decrease reduce the efficacy the drugs. In this study, the enzyme assays indicate that darunavir and tipranavir exhibit the most potent inhibition against the multi-drug …
Single Molecule Studies Of Rna-Target Interactions, Sharla Leann Wood
Single Molecule Studies Of Rna-Target Interactions, Sharla Leann Wood
Wayne State University Dissertations
We have used FRET, single molecule spectroscopy, and several other biophysical techniques to study how the folding of RNA allows it to perform its various functions by recognizing and binding a target ligand. We have shown that the c-di-GMP riboswitch undergoes a large, global conformational change upon binding of the ligand. The folding dynamics of the c-di-GMP riboswitch upon Mg2+ binding help to pre-organize the aptamer for efficient ligand binding and ultimately efficient gene expression. We have also investigated two instances, a fluorophore-binding aptamer and molecular beacon, where the folding of RNA can be used to detect an analyte. We …
Intervention Of Non-Small Cell Line Cancer Oncogenic Pathways With Delta-Tocotrienol, Xiangming Ji
Intervention Of Non-Small Cell Line Cancer Oncogenic Pathways With Delta-Tocotrienol, Xiangming Ji
Wayne State University Dissertations
Non-small cell lung cancer (NSCLC) is most hostile and leading cause of cancer deaths in the United States. Clinical data has demonstrated that 30 % of NSCLC patients have increased Notch activity and 10% of NSCLC have gain-of-function mutation on Notch-1 gene. Our data demonstrated that delta-tocotrienol could inhibit NSCLC cells proliferation, invasion and induce apoptosis by down-regulation of the Notch-1 signaling pathway. Using microRNA microarray and microRNA transfection, our findings further suggest that delta-tocotrienol is a non-toxic activator of miR-34a which can inhibit NSCLC cell proliferation, induce apoptosis, and inhibit invasion. Last but not the least, We observed that …
Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame
Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame
Wayne State University Dissertations
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron death and a corresponding loss of neuromuscular connections resulting in muscle atrophy. Patients become paralyzed shortly after symptom onset and typically die within one to five years of pulmonary complications. ALS is a relatively rare disease, with an overall incidence of approximately 2 in 100,000 people per year and a prevalence of about 5 in 100,000 people. It is typically associated with increasing age and has a slight male prevalence, with a male to female ratio of approximately 3:2. ALS is classified as either familial (the less …
Transfer Rna Dynamics And Transfer-Messenger Rna Accommodation In Bacterial Ribosomes At The Single-Molecule Level, May Daher Farhat
Transfer Rna Dynamics And Transfer-Messenger Rna Accommodation In Bacterial Ribosomes At The Single-Molecule Level, May Daher Farhat
Wayne State University Dissertations
Single-molecule spectroscopy, protein-induced fluorescence enhancement (PIFE), fluorescence resonance energy transfer (FRET), and several biochemical tools were applied to study transfer RNA (tRNA) dynamics and transfer-messenger RNA (tmRNA) accommodation inside ribosomes. In the first project of this thesis work, structural characterization of the tRNA-like domain of tmRNA (TLD) in complex with SmpB protein was carried out, and the results reveal no change in the global conformation or the flexibility of the TLD upon SmpB binding. In contrast, magnesium ions induce a compaction of the TLD structure, suggesting that flexibility in the H2a stem of TLD may allow different conformations of tmRNA, …
Analysis Of Gene Expression Alterations In Premalignant Progression From Normal Mammary Epithelium To Ductal Carcinoma In Situ By Multiple Orthogonal Tools, Hitchintan Kaur
Wayne State University Dissertations
Mammary ductal carcinoma in situ (DCIS) is being found in great numbers of women due to the widespread use of mammography. The molecular and genetic changes underlying the progression from normal breast tissue to DCIS are not clearly understood. The goal of the present study was to determine gene expression changes in different DCIS models (MCF10.DCIS, SUM102 and SUM225) in comparison to normal breast epithelial cells (MCF10A) that may enable us to identify novel markers of disease progression and potential therapeutic targets. We cultured the cells in three dimensional reconstituted basement membrane (3D rBM) for RNA extraction and used the …
Dioecious Plants: Evolution And Sex Ratio And Asepen Decline, Jordan P. Sinclair
Dioecious Plants: Evolution And Sex Ratio And Asepen Decline, Jordan P. Sinclair
Wayne State University Dissertations
Although dioecious species are rare in nature, the sexual system appears in a diverse number of families and across all life forms and global locations. We looked at the population dynamics of natural populations to determine why many dioecious populations display biased sex ratios. We also looked at the role incestuous matings, seed and pollen dispersal patterns, and compensation play in the evolution of this sexual system using two theoretical models we developed. Finally, we studied aspen populations in the Midwest to determine how climate variables affect growth and decline. We found many dioecious species display male biased ratios and …
Mechanistic Studies Of A Novel Ppar-Gamma Mutant That Causes Lipodystrophy And Diabetes, Olga Astapova
Mechanistic Studies Of A Novel Ppar-Gamma Mutant That Causes Lipodystrophy And Diabetes, Olga Astapova
Wayne State University Dissertations
PPAR-gamma is a nuclear receptor that plays a central role in metabolic regulation by regulating extensive gene expression networks in adipose, liver, skeletal muscle and many other tissues. Human PPAR-gamma mutations are rare and cause a monogenetic form of severe type II diabetes with metabolic syndrome, known as familiar partial lypodystrophy. The E157D PPAR-gamma mutant causes atypical lipodystrophy in a large Canadian kindred, presenting with multiple musculoskeletal, neurological and hematological abnormalities in addition to the classic lipodystrophy features of insulin-resistant diabetes, hypertension and dyslipidemia. This mutation is localized to the p-box of PPAR-gamma, a small region that interacts directly with …
The Methuselah Family Of G Protein Coupled Receptors, Meghna V. Patel
The Methuselah Family Of G Protein Coupled Receptors, Meghna V. Patel
Wayne State University Dissertations
G protein-coupled receptors (GPCRs) are one of the largest class of transmembrane signaling proteins that regulate essential developmental and physiological processes in a cell. GPCR success is illustrated by their abundance across both invertebrate and vertebrate genomes. Phylogenetic analyses show that GPCR families have undergone a lot of gene gain and loss during insect evolution. In Drosophila melanogaster, the fifteen Methuselah/Methuselah-like (Mth/Mthl) genes are in fact an insect specific family of GPCRs. In our study, we conducted a phylogenetic analysis using receptor sequences from five Drosophila species and two related insects, including Tribolium and Anopheles to examine the evolution of …
The Role Of Cad,Flash And Fam129b In Cancer Cell Survial And Apoptosis, Song Chen
The Role Of Cad,Flash And Fam129b In Cancer Cell Survial And Apoptosis, Song Chen
Wayne State University Dissertations
Apoptosis is a normal process in the human body. However, apoptosis is desregulated in cancer cells. Most cancer cells gain resistance to apoptosis, leading to uncontrolled proliferation. In this dissertation, we identified three proteins, associated with apoptosis pathway. 1) CAD, a large multifunctional complex that is invariably elevated in tumor cells, 2) FLASH, a large protein with multiple growth related functions and 3) FAM129B. We demonstrate that CAD could interact with FLASH by using yeast two hybrid, co-immunopreciptation and fluorescence microscopy. In addition, functional analysis using siRNA technology further indicated that CAD could co-operate with FLASH and play roles in …
Phylogenetic Utility Of Mitochondrial And Nuclear Genes: A Case Study In The Diptera (True Flies), Jason Caravas
Phylogenetic Utility Of Mitochondrial And Nuclear Genes: A Case Study In The Diptera (True Flies), Jason Caravas
Wayne State University Dissertations
The value of mitochondrial versus nuclear gene sequence data in phylogenetic analysis has received much attention without yielding definitive conclusions. Theoretical arguments and empirical data suggest a lower phylogenetic utility than equivalent nuclear gene sequences, but there are also many examples of important progress made using mitochondrial sequences. We therefore undertook a systematic performance analysis of mitochondrial and nuclear sequence partitions taken from a representative sample of dipteran species. For phylogenetic tree reconstruction, mitochondrial genes performed generally inferior to nuclear genes. However, the mitochondrial genes resolved branches for which nuclear genes failed. Moreover, the combined use of mitochondrial and nuclear …
Molecular Mechanisms Of Strain-Stimulated Intestinal Epithelial Cell Differentiation And Migration, Lisi Yuan
Molecular Mechanisms Of Strain-Stimulated Intestinal Epithelial Cell Differentiation And Migration, Lisi Yuan
Wayne State University Dissertations
The intestinal epithelium is subjected to repetitive deformation during normal gut function by peristalsis and villous motility. In vitro, cyclic strain promotes intestinal epithelial proliferation and induces an absorptive phenotype characterized by increased dipeptidyl dipeptidase (DPPIV) expression. Schlafen 3 is a novel gene recently associated with cellular differentiation. We sought to evaluate whether Schlafen 3 mediates the effects of strain on the differentiation of IEC-6 intestinal epithelial cells in the absence or presence of cyclic strain. Strain increased Schlafen 3 mRNA and protein. In cells transfected with a control non-targeting siRNA, strain increased DPPIV specific activity. However, Schlafen
3 reduction …
Gene Duplication And The Evolution Of The Higher Diptera, Riyue Bao
Gene Duplication And The Evolution Of The Higher Diptera, Riyue Bao
Wayne State University Dissertations
Gene duplication is an important source of evolutionary innovation. Using the publicly available genomic information, I studied lineage-specific gene duplications in Drosophila melanogaster (fruit fly), Anopheles gambiae (mosquito), Tribolium castaneum (red flour beetle), and Apis mellifera (honey bee) at three scales: eye-specific genes, developmental genes, and genome-wide. All three studies consistently show that the Drosophila genome contains an exceptionally high number of lineage-specific yet ancient gene duplicates, the majority of which must have originated during the early diversification of the higher Diptera (Brachycera) at least 100 million years ago. Genetic data suggest that gene duplication played an important role in …
In Vivo Display: A Selection And Its Derivatives For Antimicrobial Peptide Lead Identification, Wesley David Colangelo
In Vivo Display: A Selection And Its Derivatives For Antimicrobial Peptide Lead Identification, Wesley David Colangelo
Wayne State University Dissertations
The rise of antibiotic resistance necessitates new approaches for the isolation of new antimicrobials with novel inhibitory mechanisms, bypassing the development of rapid resistance by modification of pre-existing resistance mechanisms. In response, we have developed a series of systems for the rapid isolation and identification of peptides that inhibit the growth of Escherichia coli and other bacteria, termed in vivo display (IVD).
IVD harnesses the cellular processes of E. coli for the expression of a library of random peptides at the terminus of a display protein. A library of 12-amino acid random peptide sequences was added to either the C- …
Hierarchical Multi-Label Classification For Protein Function Prediction Going Beyond Traditional Approaches, Noor Al Aydie
Hierarchical Multi-Label Classification For Protein Function Prediction Going Beyond Traditional Approaches, Noor Al Aydie
Wayne State University Dissertations
Hierarchical multi-label classification is a variant of traditional classification in which the
instances can belong to several labels, that are in turn organized in a hierarchy. Functional classification of genes is a challenging problem in functional genomics due to several reasons. First, each gene participates in multiple biological activities. Hence, prediction models should support multi-label classification. Second, the genes are organized and classified according to a hierarchical classification scheme that represents the relationships between the functions of the genes. These relationships should be maintained by the prediction models. In addition, various bimolecular data sources, such as gene expression data and …
Determinants Of Cns Adult Neurogenesis Are Sex, Hormones, Mouse Strain, Age, And Brain Region, Carrie Lynn Tatar
Determinants Of Cns Adult Neurogenesis Are Sex, Hormones, Mouse Strain, Age, And Brain Region, Carrie Lynn Tatar
Wayne State University Dissertations
Multiple sclerosis is a sexually dimorphic (SD) disease that causes oligodendrocyte death but SD of glial cells is poorly studied. Here, we analyze SD of neural progenitors in 6-8wk and 6-8mo normal C57BL/6, SJL/J and BALB/c mice in the subventricular zone (SVZ), dorsolateral horn (DLC), corpus callosum (CC), and parenchyma. With a short 2 h BrdU pulse, no gender and strain differences are present at 6-8wk. At 6-8mo, the number of BrdU+ cells decreases 2-fold in both sexes, strains and regions indicating a common aging mechanism regulates BrdU incorporation. Strikingly, 2X more BrdU+ cells are found in all brain regions …
Biophysical And Biochemical Factors In The Cellular Microenvironment; Effects On Cell Migration And Invasion, Shalini Menon
Biophysical And Biochemical Factors In The Cellular Microenvironment; Effects On Cell Migration And Invasion, Shalini Menon
Wayne State University Dissertations
Cellular migration is a vital process central to many physiological events including development, immune surveillance and wound healing. However, migration and invasion are not unique to normal physiology, they are also key determinants in the progression of disease states such as cancer. Given the significance of migration it is important that we understand how the process is regulated intracellularly and the various stimuli that can promote it. Even though the role of biochemical factors in mediating migration has been studied extensively, the role of biophysical factors in modulating migration and invasion is less appreciation. The biochemical and biophysical components of …
Identification Of Transcriptional Mechanisms Downstream Of Nf1 Gene Defeciency In Malignant Peripheral Nerve Sheath Tumors, Daochun Sun
Wayne State University Dissertations
Malignant peripheral nerve sheath tumor (MPNST) is a type of soft tissue sarcoma that occurs in carriers of mutations in the neurofibromatosis type I gene (Nf1) as well as sporadically. Plexiform neurofibromas in NF1 patients have a significant risk of developing into MPNSTs leading to increased morbidity and mortality from this syndrome. Surgery is the primary intervention but it is not always effective due to the tendency of MPNSTs to infiltrate the surrounding tissue or grow in an inoperable location. Neurofibromin, the protein coded by the Nf1 gene, functions as a GTPase activating protein (GAP) whose mutation leads to constitutive …
Multifunctional Bioreducible Nanoparticles For Gene Therapy, Jing Li
Multifunctional Bioreducible Nanoparticles For Gene Therapy, Jing Li
Wayne State University Dissertations
Gene therapy is a promising therapeutic strategy to treat diseases caused by single or multiple gene mutations. Non-viral gene delivery vectors exhibit many advantages over viral vectors, including enhanced safety, versatility in choosing different types of therapeutic nucleic acids, and ease of formulation. However, low transgene efficiency and lack of targeting ability remain major challenges. Bioreducible polyplexes (polyelectrolyte complexes of disulfide-containing polycations and nucleic acids) utilize the redox potential gradient existing between extracellular space and intracellular environment as a physiological stimulus to enhance delivery of therapeutic nucleic acids to the subcellular space. Bioreducible containing polyplexes undergo intracellular reduction mediated GSH, …
Characterization Of Intracellular Interactions Between Dengue Virus And Host Proteins, Dumrong Mairiang
Characterization Of Intracellular Interactions Between Dengue Virus And Host Proteins, Dumrong Mairiang
Wayne State University Dissertations
Dengue virus is the causative agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome. About two-fifths of world population live in areas where dengue is prevalent, leading to high levels of morbidity and mortality in many areas. Currently there are no vaccines or effective treatments. The virus is transmitted from one person to another by the yellow fever mosquito, Aedes aegypti. The genome of dengue virus encodes only ten proteins implying that the virus needs to interact with and utilize several host proteins for replication. In this project, I used high-throughput yeast two-hybrid screening to identify mosquito and …
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Wayne State University Dissertations
Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …
Substance P And The Host Immune Response, Megan Elizabeth Foldenauer
Substance P And The Host Immune Response, Megan Elizabeth Foldenauer
Wayne State University Dissertations
This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.
SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …
Prevalence And Physiological Significance Of Gene Looping In Saccharomyces Cerevisiae, Banupriya Mukundan
Prevalence And Physiological Significance Of Gene Looping In Saccharomyces Cerevisiae, Banupriya Mukundan
Wayne State University Dissertations
My Ph.D. dissertation work is focused on studying the role of promoter-bound transcription initiation factors involved in gene looping. In this study we showed that the RNAP II subunit Rpb4 has a significant effect on termination of transcription. Gene looping is disrupted in the absence of Rpb4. Rpb4 shows a strong physical interaction with the Mediator subunit Srb5. Mediator subunit Srb5 crosslinked to the 5' and 3' ends of INO1 and CHA1 genes and is required for proper termination of transcription of these genes. Srb5 affected termination of transcription through its interaction with the CF1 complex. Srb5 interaction with the …
Hyperosmotic Stress Enzyme Signaling Modulates Oct4, Nanog, And Rex1 Expression And Induces Prioritized Differentiation Of Murine Embryonic Stem Cells, Jill A. Slater
Wayne State University Dissertations
HYPEROSMOTIC STRESS ENZYME SIGNALING MODULATES OCT4, NANOG,
AND REX1 EXPRESSION AND INDUCES PRIORITIZED DIFFERENTIATION OF
MURINE EMBRYONIC STEM CELLS
by
JILL SLATER
MAY 2013
Advisor: Daniel Rappolee, Ph.D.
Major: Physiology
Degree: Doctor of Philosophy
Transcription factor expression and therefore lineage identity in the periimplantation
embryo and its stem cells may be influenced by extracellular stresses,
potentially affecting pregnancy outcome. Cellular stress forces cells to suppress some
normal activities (such as protein synthesis and cell proliferation) in order to repair
stress-damaged macromolecules and restore homeostasis. Therefore, any new
activities that embryonic cells initiate while concurrently funding the demands of the
stress …
Investigation Of Posttranscriptional Regulation After Global Brain Ischemia And Reperfusion Injury, Jeffrey J. Szymanski
Investigation Of Posttranscriptional Regulation After Global Brain Ischemia And Reperfusion Injury, Jeffrey J. Szymanski
Wayne State University Dissertations
The final cause of death in most patients revived after cardiac arrest is ischemia and reperfusion (I/R) injury in the brain. Survival after brain I/R injury depends on the expression of new stress response proteins such as heat shock protein 70 (HSP70). Little is known about why recovering neurons are able to express new stress response proteins while neurons that will die can transcribe RNA but do not translated protein in early reperfusion. Previous studies suggested that the mRNA-binding protein HuR may regulate hsp70 mRNA in reperfused neurons through a novel cytoplasmic structure, the mRNA granule. To determine the roles …