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The Regulatory Role Of Interleukin-1 Receptor Associated Kinase M In Toll-Like Receptor Signaling, Hao Zhou

ETD Archive

Toll-like receptors (TLRs) are one of the major groups of pattern recognition receptors. TLRs are able to recognize the pathogen-associated molecular patterns and transduce their signals through the adaptor molecule MyD88 and members of the IL-1R-associated kinase family (IRAK1, 2, M and 4). IRAKM was previously known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signaling. However, we now found that IRAKM was also able to interact with MyD88-IRAK4 to form IRAKM Myddosome to mediate TLR7-induced MEKK3-dependent second wave NF¿B activation. As a result, the IRAKM-dependent pathway only induced expression of …

Sex-Bias In Lupus-Prone (Nzbxnzw)F1 Mice: The Interplay Of Gr1+Cd11b+ Cells, Testosterone And Genetics, Abhishek Trigunaite

ETD Archive

Systemic Lupus Erythematosus (SLE) is a prototypic systemic autoimmune disorder predominantly (9:1) targeting females. Currently, there is no cure for SLE and also there is a lack of disease predicting biomarkers. The major aim of my research is to determine the cellular basis of the sex bias in SLE and subsequently facilitate the development of better therapeutics and biomarkers for the disease. In (NZBxNZW) F1 mice a similar female bias is observed as in humans and testosterone is shown to be protective against lupus-like disease development, but the mechanism is not well understood.

We found higher levels of Gr1hiCD11b+ myeloid …

Calorie Restriction Effect On Circadian Clock Gene Expression, Sonal Arvind Patel

ETD Archive

Calorie Restriction (CR) is a powerful paradigm known to delay aging and thus increase longevity in several organisms, from yeast to non-human primates. Many molecular pathways have been proposed to mediate the beneficial effects of CR, however, the mechanism is still unknown. Circadian clock which is an internal time keeping system is regulated by feeding. Thus our aim was to study the effect of CR on the circadian clock. Here we show that CR significantly affects the expression of circadian clock genes in mice at the mRNA and protein levels, suggesting that CR reprograms the clocks at the transcriptional and …

Suppression Of Pulmonary Innate Immunity By Pneumoviruses, Jayeeta Dhar

ETD Archive

Pneumonia Virus of Mice (PVM) and Respiratory Syncytial Virus (RSV) are negative sense, single-stranded, enveloped RNA viruses from Pneumovirus genus, Paramyxoviridae family. RSV is the leading cause of respiratory diseases in infants. PVM causes similar respiratory illness in mice. PVM is used as an animal model to study RSV pathogenesis because of its similarity with RSV infection. Viral infection induces type I interferon (IFN) response as an antiviral strategy. PVM and RSV both have two non-structural (NS) proteins that are known to be IFN antagonists. While RSV can target different signaling components of IFN pathway, the mechanism of IFN suppression …

Effects Of Hypoxic Conditions On Skeletal Myoblasts, Shuai Zhao

ETD Archive

Hypoxic injury in skeletal muscle occurs in response to musculoskeletal traumas, diseases and following reconstructive and transplantation surgeries. However, the molecular mechanisms responsible for hypoxic injury in skeletal myoblasts have yet to be fully investigated. Understanding of these molecular mechanisms would identify potential therapeutic targets. Herein, we have determined that treatment with cobalt chloride (CoCl2, a hypoxia mimicking agent) first leads to an inhibition of proliferation followed by a decrease in the number of viable myoblasts over time. FACS analysis revealed a marked increase in G2/M arrest after 24 hours of treatment. We next assessed PARP cleavage, a well-known hallmark …

Rna-Protein Interactions In The U12-Dependent Spliceosome, Jagjit Singh

ETD Archive

Nuclear precursor messenger RNA (Pre-mRNA) splicing is an important regulatory step in metazoan gene expression. More than 99% of nuclear pre-mRNA introns are U2-type that are spliced by U2-dependent spliceosome containing U1, U2, U4, U5 and U6 snRNAs. Only less than 1% of the introns are U12-type and spliced by U11, U12, U4atac, U5 and U6atac snRNAs. U12 and U6atac snRNAs play a central role in the splicing of U12-dependent introns. Our previous work demonstrated that the conserved 3' stem-loop region of U6atac snRNA contains a U12-dependent spliceosome-specific targeting activity, however any potential molecular mechanism was unclear. We discovered that …