Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- GPCR (2)
- Schizophrenia (2)
- 5-HT2A (1)
- AAV (1)
- AML (1)
-
- ATP (1)
- Antipsychotic (1)
- Antipsychotics (1)
- Artemis (1)
- Bitter (1)
- CIAP2 (1)
- Cannabinoid (1)
- Cardioprotection (1)
- Cellular migration (1)
- Clozapine (1)
- Collagen (1)
- Complex I (1)
- Cryo-EM (1)
- Dermal fibroblasts (1)
- Dopamine D2 receptor (1)
- Double-strand break repair (1)
- EAE (1)
- Electron Transport Chain (1)
- Epistasis (1)
- Flavopiridol (1)
- Genetic code expansion (1)
- HDAC2 (1)
- Heteromer (1)
- Hydrogen sulfide (1)
- In vitro peptide synthesis (1)
Articles 1 - 12 of 12
Full-Text Articles in Entire DC Network
Impact Of Phosphoinositides On Regulation Of K-Atp By Atp And Hydrogen Sulfide, Tyler Hendon
Impact Of Phosphoinositides On Regulation Of K-Atp By Atp And Hydrogen Sulfide, Tyler Hendon
Theses and Dissertations
Hydrogen sulfide (H2S) reduces ischemia reperfusion (IR) injury by stimulating adenosine triphosphate (ATP) sensitive potassium channels (KATP) [1-5]. Demonstrating H2S stimulation is unique to KATP, as other inwardly rectifying potassium (Kir) channels demonstrate inhibition or are unaffected [6]. We recently showed that H2S inhibits Kir2 and Kir3 by decreasing channel sensitivity to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2) [6]. Here, we test the hypothesis that H2S regulation of Kir6.2, a pore-forming subunit of the KATP channel, is also dependent on PIP2. Using whole-cell patch-clamp we show that H2S increases the activity of Kir6.2 channels expressed in HEK-293 cells. To study the …
In Vitro Genetic Code Expansion And Selected Applications, Emil S. Iqbal
In Vitro Genetic Code Expansion And Selected Applications, Emil S. Iqbal
Theses and Dissertations
The ability of incorporation non-canonical amino acids (ncAAs) using translation offers researchers the ability of extend the functionality of proteins and peptides for many applications including synthetic biology, biophysical and structural studies, and discovery of novel ligands. Here we describe the three projects where the addition of ncAAs to in vitro translation systems creates useful chemical biology techniques. In the first, a fluorinated histidine derivative is used to create a novel affinity tag that allows for the selective purification of peptides from a complex mixture of proteins. In the second, the high promiscuity of an editing-deficient valine-tRNA synthetase (ValRS T222P) …
Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang
Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang
Theses and Dissertations
Cannabis (Marijuana) has multiple effects on the human body, such as analgesia, euphoria and memory impairment. Delta-9 tetrahydrocannabinol (D9-THC), the active ingredient in cannabis, binds to cannabinoid receptors, seven-transmembrane G protein-coupled receptors (GPCRs) that mediate a variety of physiological functions. GPCRs were believed to function only in homomeric forms, however, recent findings show that different GPCRs can also form heteromeric complexes that may expand their signaling properties. In this study, we focused on Cannabinoid CB1 receptor (CB1R) heteromers with the mu-opioid receptor (MOR) and the Dopamine type 2 receptor (D2R), respectively. We utilized a variety of techniques, such as the …
Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang
Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang
Theses and Dissertations
Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D2R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D2R-2AR heteromer and found that both the Gi activity of D2R and the Gq activity of 2AR were potentiated …
Processing Of 3′-Blocked Dna Double-Strand Breaks By Tyrosyl-Dna Phosphodiesterase 1, Artemis And Polynucleotide Kinase/ Phosphatase, Ajinkya S. Kawale
Processing Of 3′-Blocked Dna Double-Strand Breaks By Tyrosyl-Dna Phosphodiesterase 1, Artemis And Polynucleotide Kinase/ Phosphatase, Ajinkya S. Kawale
Theses and Dissertations
DNA double-strand breaks (DSBs) containing unligatable termini are potent cytotoxic lesions leading to growth arrest or cell death. The Artemis nuclease and tyrosyl-DNA phosphodiesterase (TDP1) are each capable of resolving protruding 3′-phosphoglycolate (PG) termini of DNA double-strand breaks (DSBs). Consequently, a knockout of Artemis and a knockout/knockdown of TDP1 rendered cells sensitive to the radiomimetic agent neocarzinostatin (NCS), which induces 3′-PG-terminated DSBs. Unexpectedly, however, a knockdown or knockout of TDP1 in Artemis-null cells did not confer any greater sensitivity than either deficiency alone, indicating a strict epistasis between TDP1 and Artemis. Moreover, a deficiency in Artemis, but not TDP1, resulted …
Modulation Of Electron Transport By Metformin In Cardiac Protection: Role Of Complex I, Ahmed Abdul Hussein Mohsin
Modulation Of Electron Transport By Metformin In Cardiac Protection: Role Of Complex I, Ahmed Abdul Hussein Mohsin
Theses and Dissertations
Modulation of mitochondrial complex I during reperfusion reduces cardiac injury. Complex I exists in two structural states: active (A) and deactive (D) with transition from A→D during ischemia. Reperfusion reactivates D→A with an increase in ROS production. Metformin preserves the D-Form. Our aim was to study the contribution of maintenance of deactivation of complex I during early reperfusion by metformin to protect against ischemia reperfusion injury. Our results showed that metformin decreased H9c2 cardiomyoblast apoptosis and total cell death following simulated ischemia for six hours followed by reoxygenation for twenty four hours compared to untreated cells. Reactive oxygen species (ROS) …
Cellular Inhibitor Of Apoptosis Protein2 – A Critical Regulator Of Neuroinflammation, Debolina Dipankar Biswas
Cellular Inhibitor Of Apoptosis Protein2 – A Critical Regulator Of Neuroinflammation, Debolina Dipankar Biswas
Theses and Dissertations
Inhibitors of apoptosis (IAPs) modulate cell death and play critical role in signal transduction that promotes inflammation. Recently, Smac mimetics, which are IAP antagonists, have attracted attention as novel cancer therapeutics. Cellular Inhibitor of Apoptosis 2 (cIAP2), a member of IAP family, positively affects both NF-κB and MAPK activation in response to many inflammatory stimuli. We observed that the lack of cIAP2 ablates LPS-induced neuroinflammation. Also, cIAP2-/- macrophages demonstrated diminished antigen presentation potential that could contribute to ablated immunity. In addition to these functions, we have previously reported that cIAP2 also regulates the activation of Interferon Regulatory Factor 1 …
Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy
Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy
Theses and Dissertations
Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT2A-dependent upregulation of histone deacetylase 2 …
The Interaction Between Ceramide-1-Phosphate And Group Iva Cytosolic Phospholipase A2 And Its Role In Wound Healing, Patrick Macknight
The Interaction Between Ceramide-1-Phosphate And Group Iva Cytosolic Phospholipase A2 And Its Role In Wound Healing, Patrick Macknight
Theses and Dissertations
The sphingolipid, ceramide-1-phosphate (C1P), directly binds and activates Group IVA cytosolic phospholipase A2 (cPLA2a) to generate eicosanoids. Due to the role of eicosanoids in wound healing, we choose to use our novel genetic mouse model expressing cPLA2a with an ablated C1P interaction site (KI) to examine the cPLA2a/C1P interaction in wound healing. Wound closure rate was not affected, but wound maturation was dramatically enhanced by loss of the C1P/cPLA2α interaction based on the following findings. Wounds in KI mice displayed: i) increased infiltration of dermal fibroblasts into the wound environment; ii …
Nicotinic Acetylcholine Receptor Dependent Effects Of Nicotine On Hek293t And Hbo Cells, James D. Larsen
Nicotinic Acetylcholine Receptor Dependent Effects Of Nicotine On Hek293t And Hbo Cells, James D. Larsen
Theses and Dissertations
T2R receptors are the classical bitter taste receptors which detect and transduce bitter taste in a subset of taste receptor cells (TRCs). The TRPM5-dependent T2Rs are G-protein coupled receptors (GPCRs) and are linked to G protein, gustducin to initiate an intracellular signaling cascade for the transduction of bitter tastants. Nicotine is bitter. However, at present the transduction mechanisms for the detection of nicotine in are poorly understood. Previous studies from our laboratory using TRPM5 knockout (KO) mice demonstrated that the T2R pathway is insufficient in explaining the taste perception of nicotine. TRPM5 KO mice elicited chorda tympani (CT) taste nerve …
Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt
Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt
Theses and Dissertations
Acute myeloid leukemia (AML) is the second most common type of leukemia and accounts for 80% of adult acute leukemia cases and is characterized by the accumulation of poorly or undifferentiated myeloid blast cells. Standard treatment includes chemotherapy, which if unsuccessful, is followed by more rigorous chemotherapy as well as stem cell transplantation. Considering most patients are over the age of 45, these more rigorous therapies are not always possible, and as such, new therapies must be developed. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) that results in the expression of an MLL fusion protein …
Rep-Dna Complexes And Their Role In Aav Dna Transactions, Vishaka Santosh
Rep-Dna Complexes And Their Role In Aav Dna Transactions, Vishaka Santosh
Theses and Dissertations
Adeno-associated Virus (AAV) Rep proteins are multifunctional proteins that carry out various DNA transactions required for the life cycle of AAV. The Rep proteins have been found to be important for genome replication, gene regulation, site-specific integration and play an essential role in genome packaging. There are two main groups of Rep proteins: large and small Reps; both groups are SF3 helicase family members. During DNA packaging, studies have shown that the small Rep proteins are critical to produce fully packed particles. Using stopped-flow kinetic analysis, we show a significant difference in helicase activity between the small and large Rep …