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Full-Text Articles in Life Sciences

Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini Jul 2019

Intron And Small Rna Localization In Mammalian Neurons, Harleen Saini

GSBS Dissertations and Theses

RNA molecules are diverse in form and function. They include messenger RNAs (mRNAs) that are templates for proteins, splice products such as introns that can generate functional noncoding RNAs, and a slew of smaller RNAs such as transfer RNAs (tRNAs) that help decode mRNAs into proteins. RNAs can show distinct patterns of subcellular localization that play an important role in protein localization. However, RNA distribution in cells is incompletely understood, with prior studies focusing primarily on RNAs that are long (>200 nucleotides), fully processed, and polyadenylated. We examined the distribution of RNAs in neurons. Neuronal compartments can be separated by ...


Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel Jul 2019

Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel

GSBS Dissertations and Theses

Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with a poor prognosis. Currently, prognosis for HCC patients remains poor as few therapies are available. The clinical need for more effective HCC treatments remains unmet partially because HCC is genetically heterogeneous and HCC driver genes amenable to targeted therapy are largely unknown. Mutations in the TP53 gene are found in ~30% of HCC patients and confer poor prognosis to patients. Identifying genes whose depletion can inhibit HCC growth, and determining the mechanisms involved, will aid the development of targeted therapies for HCC patients. Therefore, the first half of this ...


Mechanistic Basis For Control Of Early Embryonic Development By A 5’ Trna Fragment, Xin Y. Bing Jul 2019

Mechanistic Basis For Control Of Early Embryonic Development By A 5’ Trna Fragment, Xin Y. Bing

GSBS Dissertations and Theses

Ancestral environmental conditions can instruct offspring development, although the mechanism(s) underlying such transgenerational epigenetic inheritance is unclear. In murine models focused on paternal dietary effects, we and others have identified tRNA fragments (tRFs) in mature sperm as potential carriers of epigenetic information. In our search for molecular targets of specific tRFs, we observed that altering the level of 5’-tRF Glycine-GCC (tRF-GG) in mouse embryonic stem cells (mESCs) and preimplantation embryos modulates the expression of the endogenous retrovirus MERV-L and genes regulated by MERV-L. Intriguingly, transient derepression of MERV-L is associated with totipotency of two-cell stage embryos and a ...


Tcr Signal Strength Controls Dynamic Nfat Activation Threshold And Graded Irf4 Expression In Cd8+ T Cells, James M. Conley Apr 2019

Tcr Signal Strength Controls Dynamic Nfat Activation Threshold And Graded Irf4 Expression In Cd8+ T Cells, James M. Conley

GSBS Dissertations and Theses

TCR signal strength is critical for CD8+ T cell clonal expansion after antigen stimulation. Levels of the transcription factor IRF4 control the magnitude of this process through induction of genes involved in proliferation and glycolytic metabolism. The signaling mechanism connecting graded TCR signaling to the generation of varying amounts of IRF4 is not well understood. Here, using multiple methods to vary TCR signal strength and measure changes in transcriptional activation in single CD8+ T cells, we connect antigen potency to the kinetics of NFAT activation and Irf4 mRNA expression. T cells that transduce weaker TCR signals exhibit a marked delay ...


Understanding The Role Of Prdm12b In Zebrafish Development, Ozge Yildiz Mar 2019

Understanding The Role Of Prdm12b In Zebrafish Development, Ozge Yildiz

GSBS Dissertations and Theses

Function of the adult nervous system relies on the appropriate establishment of neural circuits during embryogenesis. In vertebrates, the neurons that make up motor circuits form in distinct domains along the dorsoventral (DV) axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing the fates of adjacent domains. The prdm12 TF is required for the expression of eng1b and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear.

We used CRISPR/Cas9 genome editing technology to generate the ...