Mapping the ρ1 GABAC Receptor Agonist Binding Pocket

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. The GABA receptor type C (GABAC) is a ligand-gated ion channel with pharmacological properties distinct from the GABAA receptor. To date, only three binding domains in the recombinant ρ1 GABAC receptor have been recognized among six potential regions. In this report, using the substituted cysteine accessibility method, we scanned three potential regions previously unexplored in the ρ1 GABAC receptor, corresponding to the binding loops A, E, and F in the structural model for ligand-gated ion channels. The cysteine accessibility scanning and agonist/antagonist protection tests have resulted in the identification of residues in loops A and E, but not F, involved in forming the GABAC receptor agonist binding pocket. Three of these newly identified residues are in a novel region corresponding to the extended stretch of loop E. In addition, the cysteine accessibility pattern suggests that part of loop A and part of loop E have a β-strand structure, whereas loop F is a random coil. Finally, when all of the identified ligand binding residues are mapped onto a three-dimensional homology model of the amino-terminal domain of the ρ1 GABAC receptor, they are facing toward the putative binding pocket. Combined with previous findings, a complete model of the GABAC receptor binding pocket was proposed and discussed in comparison with the GABAA receptor binding pocket

The Impact of the Ohio Lottery on Public Primary and Secondary Schools in Montgomery County

In 1974, voters in the state of Ohio approved the institution of a lottery as a means to raise funds for their public primary and secondary schools. According to the legislative history of the Ohio Lottery, the purpose for the lottery is to provide a means for relatively poor school districts to enhance their own local tax base such that more public school funds could be produced locally to meet the special needs of their primary and secondary schools. Lottery operations have been conducted in most school districts for more than a quarter of a century. For a number of relatively poor school districts in Montgomery County, the amount of local school funding derived from local lottery operations within the district is significantly less than the entitlement expressed in the legislative history of the Ohio Lottery. Under the present formula used to allocate lottery profits, there is no correspondence between lottery revenue and profit generated within a district. The resultant pricing policy, which involves the bundling of a game of chance for players to win money and provisions for additions to players’ local tax bases, has caused an increase in the unit cost of public primary and secondary education in poorer school districts in Montgomery County. Additionally, the formula has precipitated a broadening of the disparity between educational opportunities for youth in poor districts and youth in relatively affluent districts. The focus of this research report is on Ohio Lottery operations for the year of 1997. A primary inquiry is whether the lottery is a regressive tax in Montgomery County. My approach will involve an examination of the effects the redistribution policy had on the sixteen school districts in Montgomery County. I will also address the trade-off involved in subsidizing some of the sixteen school districts in Montgomery County while attempting to motivate low-income households to increase their lottery expenditures

A study of the social schema of normal and hard of hearing young adults

Includes bibliographical references.Includes illustrations.The purpose of this study was to determine whether or not hard of hearing and normal young adults, would show a social schema when presented human figure cut-outs. Further consideration was given to the question: Is there a significant difference between males and females in terns of their social schema. Twenty hard of hearing young adults were selected and matched with twenty normal hearing young adults. The age range for both groups was 17-21. A 40 by 40 inches square flannel board in addition with human figures, cut from felt material, were the instruments used to test the subjects. The subjects were presented six sets of human figure cut-outs. For each set they were instructed to imagine a scene concerning these figures and then place them on the field to represent the main idea of the scene. Following their performance, they gave a one word title that was suggestive of their scene. The verbal response and the distance between the figures were recorded. The results revealed: (1) that the hard of hearing subjects placed the human figures closer together than did the normal subjects; (1) that the female subjects perceived the figures as being significantly different from each other within the varying sots. Analysis of the oral responses showed the hard of hearing group to perceive favorable interaction of people and/or situations as they really are in everyday life. Their responses also suggested family relationship interaction.M.A. (Master of Arts

The tectonic relationships of the Hillabee Chlorite Schist and the adjacent rock units in southern Cleburne County, Alabama

Southern Cleburne county Alabama contains two defined litho-tectonic blocks separated by a large displacement thrust fault. The Talladega block is composed of low grade metamorphic rocks. Sericite Phyllites and Quartzites are the main composition units. Metamorphic and tectonic events have created four defined structural events that are mapped in the block. The Hillabee Chlorite Schist, a low grade metamorphic unit lies conformable and the youngest unit in the Talladega block. Geochemical analysis indicates the origin to be in an island arc environment. The Coosa Block is thrust over the Talladega clock. The Hollins line fault is the contact between the Talladega and Coosa Blocks. The Coosa Block is composed of high grade Amphibolites facies rocks. Mica Schist with garnet and kyanite are interbedded with Amphibolites composing this block. Deformation along the Hollins line Fault creates a sercite phyllite in the high grade metamorphic Coosa Block unit. These phyllites include garnet that defines the contact between the two blocks and the placement of the Hollins line fault. (Published By University of Alabama Libraries

Investigation on the basin-scale factors of bedrock shoals distribution in the Flint River, Georgia, USA

Bedrock outcrops create shoaled sections in many rivers of the eastern United States. Bedrock shoals can consist of a variety of channel morphologies and lithologies and are important forms of river habitat by having higher species richness than other locations along the same river. Despite their ecological significance, the system-scale factors that determine their occurrence in rivers are not well understood. In this study, shoaled and non-shoaled sites along the length of the upper Flint River, Georgia, were analyzed to determine the factors responsible for the presence of shoals. Strike-flow ratio, rock integrity, confinement ratio, unit stream power, and geologic dip were selected as possible variables based on existing literature and observations on bedrock shoals and general bedrock morphology. The results of a logistic regression showed that confinement ratio and unit stream power were the most statistically significant predictors of a river reach’s shoal status (p=0.001 and 0.014, respectively), suggesting that variables comprising the driving forces in the Flint River currently dominate system-scale expression of channel morphology. A predictive equation developed from the binary logistic regression analysis correctly classified 80% of known shoaled sites as “shoaled locations” in the watershed and 60% of known non-shoaled sites as “non-shoaled locations” in the watershed. While these results are promising and suggest that system-scale heterogeneity of channel morphology may be controlled by spatial variability of confinement ratio and unit stream power, there is room for improvement, particularly in regard to correct classification of non-shoaled locations. In comparing the findings of this research to those previously made on bedrock shoal occurrence in the Cahaba River, Alabama (Bishop, 2013) – visually similar to the Flint River – questions arise concerning the prevailing view of how dynamic equilibrium operates in fluvial geomorphic systems. Although the Cahaba and Flint Rivers contain bedrock shoal morphologies for long expanses, the occurrence of bedrock shoals in the Flint River are controlled by driving forces, while bedrock shoals in the Cahaba River are controlled by resisting forces. This finding supports the idea that dynamic equilibrium, a state of balance between driving and resisting forces, may be temporally and spatially limited in geomorphic systems. (Published By University of Alabama Libraries

Selective Ablation of Dehydrodolichyl Diphosphate Synthase in Murine Retinal Pigment Epithelium (RPE) Causes RPE Atrophy and Retinal Degeneration

Patients with certain defects in the dehydrodolichyl diphosphate synthase (DHDDS) gene (RP59; OMIM #613861) exhibit classic symptoms of retinitis pigmentosa, as well as macular changes, suggestive of retinal pigment epithelium (RPE) involvement. The DHDDS enzyme is ubiquitously required for several pathways of protein glycosylation. We wish to understand the basis for selective ocular pathology associated with certain DHDDS mutations and the contribution of specific ocular cell types to the pathology of mutant Dhdds-mediated retinal degeneration. To circumvent embryonic lethality associated with Dhdds knockout, we generated a Cre-dependent knockout allele of murine Dhdds (Dhddsflx/flx). We used targeted Cre expression to study the importance of the enzyme in the RPE. Structural alterations of the RPE and retina including reduction in outer retinal thickness, cell layer disruption, and increased RPE hyper-reflectivity were apparent at one postnatal month. At three months, RPE and photoreceptor disruption was observed non-uniformly across the retina as well as RPE transmigration into the photoreceptor layer, external limiting membrane descent towards the RPE, and patchy loss of photoreceptors. Functional loss measured by electroretinography was consistent with structural loss showing scotopic a- and b-wave reductions of 83% and 77%, respectively, at three months. These results indicate that RPE dysfunction contributes to DHDDS mutation-mediated pathology and suggests a more complicated disease mechanism than simply disruption of glycosylation