Thesis (Ph. D.)--University of Missouri-Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 151-180). Also available on the Internet.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 127-139). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Missouri-Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 151-180). Also available on the Internet.

The Reelin signaling pathway is critical for neuronal migration during development and the function of excitatory synapses in the adult forebrain. Despite a growing body of evidence implicating impaired Reelin signaling in the pathogenesis of numerous neuropsychiatric and neurodegenerative disorders, including Schizophrenia and Alzheimer's disease, little is known still regarding the specific molecular and cellular mechanisms whereby Reelin signaling modulates the function of synapses to enable normal learning and memory. In this dissertation, we addressed these knowledge gaps by identifying mechanisms of Reelin proteolysis following synaptic potentiation (Chapter 2) and dissociated the synaptic function of Reelin signaling at excitatory (Chapter 3) and inhibitory synapses (Chapter 4). In the adult brain, Reelin is secreted by GABAergic interneurons into the extracellular space, after which it is cleaved by unknown proteases to generate active fragments that signal downstream. In Chapter 1, we demonstrate that tissue plasminogen activator (tPA) and its major in vivo substrate, plasminogen, cleave Reelin under cell-free conditions to generate major Reelin fragments found in vivo. Since manipulation of tPA levels under basal conditions had no effect on Reelin processing, we hypothesized that synaptic activity may be required to render Reelin susceptible to proteolysis by tPA. Indeed, the modulation of Reelin processing by synaptic potentiation of ex vivo hippocampal slices required the presence of tPA. These data are the first to demonstrate a specific context in which Reelin signaling may be initiated in the intact brain and further emphasize that extracellular proteolysis of Reelin by tPA and other yet-to-be identified proteases is important to consider when trying to understand how altered Reelin processing and/or expression contribute to cognitive impairments associated with disease states. In Chapters 2 and 3 of this dissertation, we describe recent attempts by our lab to elucidate cellular mechanisms of Reelin signaling in the adult brain. To do this, we generated two conditional knockout mutants that lack the obligate downstream adaptor protein, Disabled-1 (Dab1), specifically in postnatal excitatory neurons (eKO) or GABAergic interneurons (iKO). Despite some overlap of Reelin and Dab1 in a subset of GABAergic interneurons, we found that their expression was generally juxtaposed, with Dab1 being primarily expressed by principle neurons and a more widespread population of Reelin-negative GABAergic interneurons. While eKO mice exhibited normal forebrain lamination, dendritic architecture, and dendritic spine density, they did have reductions in spine volume and a loss of basal and activity-dependent Akt and MAPK activation. These changes culminated in impairments in short-term and long-term synaptic plasticity, as well as impairments in associative learning and spatial memory. Taken together, our observations in the eKO mice are the first to definitively establish a synaptic function of Reelin signaling in the adult hippocampus. While characterizing the eKO mice, we also observed that GABAergic interneurons expressed Dab1, which motivated us to explore the inhibitory synapse as a novel locus of Reelin signaling (Chapter 4). Although loss of Dab1 in GABAergic interneurons did not affect forebrain development or the overall patterning of inhibitory synapses, iKO mice presented with an ataxic gait, resting tremor and cerebellar hypoplasia. Interestingly, loss of Dab1 in interneurons led to altered expression of some major glutamatergic synapse proteins (i.e. NMDA receptor subunits NR1 and NR2B), while other excitatory and inhibitory synapse proteins were normal (e.g. NR2A, GAD67/65, and gephyrin). Hippocampal field recordings further demonstrated that even partial loss of Dab1 expression in iHET mice, led to enhanced presynaptic activation and impaired theta-burst induced LTP. These data establish the inhibitory synapse as a novel locus of Reelin signaling in the developing and adult brain. Taken together, data discussed herein should prove useful for understanding and treating disorders associated with Reelin signaling impairments (e.g. AD and Schizophrenia).

This experimental study was conducted to examine the relative effectiveness of a Repeated Reading (RR) and Wide Reading (WR) intervention when compared to typical instruction on secondary struggling readers' comprehension, fluency, and word reading. The sample consisted of a total of 96 students (9th through 12th grade) ranging in age from 13-17 in special education reading and English classrooms. Participants included students with learning disabilities (LD), dyslexia, or students selected as students with significant reading difficulties. The investigator paired students on variables of interest (i.e., reading level) within classes and then randomly assigned pairs to one of three groups: repeated reading (N=33), wide reading (N=34), or typical instruction (N=29). Tutors, trained by the investigator, monitored students as they worked in pairs in each treatment condition. Intervention was provided daily for approximately 15-20 minutes for 10 weeks. Treatment effects for each outcome measure were estimated using analysis of covariance (ANCOVA). Results indicate no overall statistically significant differences for any condition. Effects ranged from -.81 to .28 usually hovering around no effect or favoring the C condition over the treatment conditions or favoring the RR condition over the WR condition. Five separate ANCOVAs were conducted using the following dependent variables with each pretest score used as a covariate: (1) Woodcock Johnson Tests of Achievement III (WJIII) Passage Comprehension subtest (RR vs. C = -.10; WR vs. C = -.20; RR vs. WR= .10); (2) Test of Silent Reading Fluency (TOSRE) (RR vs. C =.-31; WR vs. C = -.81; RR vs. WR= .10); (3) Woodcock Johnson Tests of Achievement III (WJIII) Letter-Word Identification subtest (RR vs. C = -.05; WR vs. C = -.11; RR vs. WR = .06); (4) AIMSWeb Oral Reading Fluency System (RR vs. C = -.08; WR vs. C = -.26; RR vs. WR= .18); and (5) Test of Silent Contextual Reading Fluency (RR vs. C =.28; WR vs. C = -.01; RR vs. WR= .28). Results indicate that neither RR nor WR should be implemented for secondary readers with significant reading difficulties and more research into ways to make fluency instruction more explicit and instructional for these students is warranted.

Not available / text

published_or_final_version / Education / Master / Master of Education

The present study examined the impact of the Verterans Administration disability compensation system on the personality and behavior of psychiatrically disabled veterans who receive compensation payments. Weinstein proposed a "disability process" model in which physical illness or injury was unwittingly utilized as a solution to a network of problems centering on frustrated dependency needs, decreased productivity, and faltering self-esteem. An attempt was made to determine whether Weinstein's model applies to the psychiatric disabilities of veterans. Seventy-one male psychiatric outpatients seen at the Tucson Veterans Administration Medical Center participated in the study. Of this total, 26 had been receiving 100 percent service-connected compensation payments ($809 per month) for at least the past five years (100 percent group), 21 had been receiving between 10 percent and 90 percent payments ($44 to $450 per month) during the same period (10-90 percent group), and 24 had received no Veterans Administration compensation for their psychiatric impairments in the apst five years (UNC group). Personality questionnaires, a self-report demographics questionnaire, and a records search were utilized to compare these three groups. The main hypotheses contended that 10-90 percent group members weould be more self-critical and would view themselves as more psychologically disturbed and externally controlled than members of the other two groups, as they were assumed to be unconsciously fighting to establish the validity and extent of their disabilities. Subjects in the UNC group were hypothesized to be the healthiest psychologically because it was assumed that they had not become enmeshed int he "disability process". On 20 of the 21 subscales meauring some form of psychological distress, no significant differences among groups were uncovered. There were also no differences among groups on the internal-external locus of control dimension. These findings failed to support the hypothesis that the 10-90 percent group would see themselves as most psychologically disturbed and externally controlled. The expectation that 10-90 percent group members would be most self-critical was directly contradicted, as on three of ten subscales subjects in the 10-90 percent group reported significantly more positive self concepts than members of the other two groups. Despite the fact that they were rated for compensation purposes as "totally disabled," 100 percent group members reported no more psychological distress than subjects in the other two groups (with the exception that they reported significantly more hostility than UNC group members). However, both the attainment of inital 100 percent compensation status and of a permanent 100 percent rating led to significant reductions in the number of days 100 percent group members spent in the hospital (when the year after the rating change was compared with the year before). In addition, when they worked, subjects int he 100 percent group were employed in lower status occupations than members of the other two groups. UNC group members were shown to be similar to 100 percent group members on most assessment measures. However, during the past five years UNC group members were hospitalized significantly more times and for significantly more days than subjects in either of the other two groups. A direct discriminant function analysis generated two functions which together correctly classified 74.6 percent of the subjects. An unrotated factor analysis yielded factors descriptive of psychiatrically disabled veterans as a group. An alternative disability process model was proposed that may be more applicable to a psychiatrically impaired population. Also, future research projects were suggested including some possible experimental modifications in the Veterans Administration compensation system that might make it more beneficial to the mental health and self-esteem of psychiatrically impaired veterans, while maintaining cost efficiency.

Coping behaviour, perceived control, and the self concept of elementary school children with learning disabilities educated in regular and special education classrooms was examined using a comparative design. In addition, the influence of teachers' classroom management orientation on children's self-perceptions and coping behaviour was investigated. Children attending a special school for students with learning disabilities were found to be more adaptive copers than children in special education classes in regular schools, children receiving resource room assistance, and children mainstreamed in regular classes. Children with learning disabilities were found to have positive perceptions of their global self-worth regardless of the type of class they were in, although they indicated less confidence in their academic abilities compared to their self-perceptions of physical appearance and athletic competence. In general, most children believed that they were responsible for their academic successes and at the same time perceived academic failure as unavoidable. The students who coped most effectively demonstrated the most realistic appraisals of their academic situation. They recognized that they could not control academic failure, however, they believed that the best way to succeed in school was by continuing to exert effort. Additionally, successful copers held high expectations for future academic success and believed that they possessed the capacities needed to achieve this success. Children who coped most effectively strongly endorsed beliefs in their capacity to have a positive relationship with their teachers. Children who were rated as effective copers had teachers whose instructional orientation promoted autonomous functioning in their students.

Sergančiųjų įvairiomis psichikos ligomis nemažėja tiek pasaulyje, tiek Lietuvoje, o aplinkos veiksniai, tokie kaip ekonominis nestabilumas, bedarbystė ir kita, skatina šių sutrikimų didėjimą. Be psichinio funkcionavimo problemų psichikos ligos beveik visada sukelia socialinio funkcionavimo sutrikimus. Sergančiųjų savarankiškumo atstatymui ir jų visavertei integracijai į visuomenę svarbi psichosocialinė reabilitacija, kurios pagrindiniai etapai – intensyvi klinikinė reabilitacija, kol pacientas gydomas ligoninėje, ir socialinių paslaugų teikimas bendruomenės institucijose. Šio darbo tikslas – išanalizuoti ir palyginti žmonių su psichikos sutrikimais reabilitacijos būdus ir galimybes bendruomenėje ir stacionarioje gydymo įstaigoje (Respublikinėje Vilniaus psichiatrijos ligoninėje). Pirmoje darbo dalyje pateikta psichosocialinės reabilitacijos samprata ir svarba, supažindinta su psichiatrijos ligoninėje ir bendruomenėje teikiamomis psichosocialinės reabilitacijos paslaugomis. Tiriamojoje dalyje pateikiami atlikto tyrimo rezultatai. Paaiškėjo, kad asmenys, turintys psichikos sutrikimų, gydydamiesi ligoninėje gauna pakankamai informacijos ir įsitraukia į įvairias reabilitacines užimtumo veiklas pagal saviraiškos poreikius. Tuo tarpu, užimtumo veikloje bendruomenės institucijose dalyvauja ženkliai mažiau tiriamųjų nei ligoninėje. / The number of people with mental trouble has not been decreasing in the whole world as well as in Lithuania. Moreover, the environmental factors such as economical instability, unemployment and other determine the increase of this kind of disorder. Apart from disorder of mental behavior mental diseases almost always evoke disorder of social behavior. Psychosocial aftercare is very important for reestablishment of independency and proper integration of the sick into the society. The main stages of the psychosocial aftercare are intense clinical aftercare while the patient is treated in hospital and social services in community institutions. The goal of the thesis is to analyze and compare different aftercare methods and opportunities in the community and stationary medical institutions (Republican Vilnius psychiatric hospital) for mentally disabled people. The conception and importance of psychosocial aftercare are presented in the first part of the thesis. Moreover, psychosocial aftercare services supplied in psychiatric hospitals and communities are revealed. The second part discloses the results of the research. It has been established that people with mental disability get enough information in hospitals and get involved into different activities of aftercare according to needs of self-expression. On the other hand, less people participate in aftercare activities in community institutions if compared with hospitals.