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Articles 31 - 39 of 39
Full-Text Articles in Medicine and Health Sciences
Dynamics Of Substrate Interactions In Trna (M1g37) Methyltransferase: Implications For Drug Discovery, Maria Kiouppis Palesis
Dynamics Of Substrate Interactions In Trna (M1g37) Methyltransferase: Implications For Drug Discovery, Maria Kiouppis Palesis
Theses and Dissertations
The bacterial enzyme t-RNA (m1G37) methyltransferase (TrmD) is an ideal anti-microbial drug target since it is found in all eubacteria, serves an essential role during protein synthesis, and shares very little sequence or structural homology with its eukaryotic counterpart, Trm5. TrmD, a homodimeric protein, methylates the G37 nucleotide of tRNA using S-adenosyl-L-methionine (SAM) as the methyl donor and thus enables proper codon-anticodon alignment during translation. The two deeply buried binding sites for SAM seen in X-ray crystallography suggest that significant conformational changes must occur for substrate binding and catalytic turnover. Results from molecular dynamics simulations implicate a flexible loop region …
Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz
Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz
Theses and Dissertations
Fetal alcohol spectrum disorder is the leading cause of mental retardation in the western world. It is associated with learning and sensory deficits. Some of these deficits are a result of faulty neuronal plasticity. Previously our lab has used ferrets to demonstrate that alcohol exposure during the third trimester of human gestation results in impaired ocular dominance plasticity (ODP). Here we have transferred this model to mice. Mice, treated with 5 mg/kg of ethanol on postnatal days 5, 7 and 9, exhibit a lack of ODP plasticity after 10 days of monocular deprivation (MD) during the critical period of visual …
Quantitative Genetic Methods To Dissect Heterogeneity In Complex Traits, T. Bernard Bigdeli
Quantitative Genetic Methods To Dissect Heterogeneity In Complex Traits, T. Bernard Bigdeli
Theses and Dissertations
Etiological models of complex disease are elusive[46, 33, 9], as are consistently replicable findings for major genetic susceptibility loci[54, 14, 15, 24]. Commonly-cited explanations invoke low-frequency genomic variation[41], allelic heterogeneity at susceptibility loci[33, 30], variable etiological trajectories[18, 17], and epistatic effects between multiple loci; these represent among the most methodologically-challenging issues in molecular genetic studies of complex traits. The response has been con- sistently reactionary—hypotheses regarding the relative contributions of known func- tional elements, or emphasizing a greater role of rare variation[46, 33] have undergone periodic revision, driving increasingly collaborative efforts to ascertain greater numbers of participants and which assay …
Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra
Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra
Theses and Dissertations
DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient …
Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar
Theses and Dissertations
Neuronal nicotinic acetylcholine receptors modulate both cholinergic and non-cholinergic synaptic transmission. Our research concerns α6 and α4 neuronal nicotinic subunits because they often co-assemble with the β2 subunit, which has abundant expression in the CNS and previous work has demonstrated that β2* nAChRs are involved in nicotine and cocaine reward. α6β2* and α4β2* nAChRs are highly expressed in midbrain, which is known to be critical for the incentive salience associated with natural and artificial (drug) reward. Our goal was to assess the role of α6β2* and α4β2* nAChRs in nicotine and cocaine reward using an unbiased conditioned place preference (CPP) …
The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall
The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall
Theses and Dissertations
Tobacco dependence is high in women who suffer from anxiety disorders yet little is known about the contributions of nicotinic acetylcholine receptors (nAChRs) on anxiety-like behavior. β2*nAChRs (*denotes assembly with other subunits) are the most abundantly expressed nAChRs in the brain yet little is known about the contributions of β2*nAChRs on anxiety-like behavior in female mice. In this study, antagonism and nicotine effects on anxiety-like behavior was investigated across the life span in 6, 12 and 24-month-old drug-naïve knockout (KO), heterozygous (HET) and a gain of function α6L9S mice and wild type (WT). HET mice showed increased sensitivity to di-hydrobeta-erythroidine …
Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook
Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook
Theses and Dissertations
The visual system is one of the most widely used and best understood sensory systems and the dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model for investigating the cellular and molecular mechanisms underlying the development and activity-dependent refinement of sensory connections. Thalamic organization is highly conserved throughout species and the dLGN of the mouse possesses many features common to higher mammals, such as carnivores and primates. Two general classes of neuron are present within the dLGN, thalamocortical relay cells and interneurons, both of which receive direct retinal input. Axons of relay cells exit dLGN and …
Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn
Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn
Theses and Dissertations
Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …
Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh
Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh
Theses and Dissertations
The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …