Syftet med denna studie var att undersöka vilka faktorer som är betydelsefulla för att stödja personer med intellektuell funktionsnedsättning i att erhålla anställning. Fem personal som stödjer personer med intellektuell funktionsnedsättning i processen att erhålla anställning samt fyra personer som tar emot stöd avseende detta har intervjuats. Materialet har bearbetats utifrån en induktiv tematisk analysmetod med empowerment som teoretisk ansats. Huvudresultatet visade att det var viktigt att genomföra individuellt anpassad kartläggning samt stödja utifrån motivation. Handledaren bör arbeta med inkludering, ta parti för personer med intellektuell funktionsnedsättning, utveckla personens förmågor och självmedvetenhet. Att vänja samhället vid dessa personer samt att bidra med positiva förväntningar framkom också som viktigt. Slutsatsen är att ett empowermentarbete är framgångsrikt för att hjälpa personer med intellektuell funktionsnedsättning att erhålla arbete samt vid behov erbjuda fortsatt handledningsstöd för att hjälpa intellektuellt funktionsnedsatta att också behålla arbetet. / The purpose of this study was to examine important factors during support for people with intellectual disability to obtain employment. Five professionals who are supporting people with intellectual disabilities in the process towards work and four individuals that have received employment support have been interviewed. An empowerment perspective and inductive thematic method has been used to analyze the material. The results showed the importance to adjust support and evaluation individually. Client inclusive support, the work with motivation and advocating for people with disability are all important factors. To support development of skills and self awareness, to accustom society to people with disability and contribute to positive expectations are also central aspects. The conclusion has shown that empowerment-based support is a successful way of helping people with intellectual disability to receive employment. Also when needed, be able to offer continued support when employment has been established to help people retain employment.

The overall aim of this thesis was to investigate pregnancy and childbirth in women with intellectual disability (ID), in Sweden, the health of their newborns and midwifery care for these women. Two register studies and two descriptive studies are included. Pregnancy and birth outcomes as well as data on the newborns’ health were examined by linking data from the National Patient Register and the Medical Birth Register (I-II). The women’s experience of pregnancy and delivery was investigated with repeated interviews (III). Midwives’ knowledge of, experience of and attitudes towards pregnancy and childbirth in women with ID were evaluated with questionnaires (IV). Mothers with ID were more often teenagers, smoked more during pregnancy and had more Caesarean Sections. Their children had a higher proportion of pre-term births, were small-for-gestational-age, stillborn or died in the perinatal period. The women with ID struggled to attain motherhood and feared to lose custody of the child. The pregnancy was seen as a happy event, even though relatives did not always approve. Parent education was considered important, but not adequately adapted to their needs. The birth process was overwhelming and difficult to understand, but the child was welcomed with warm feelings, and breastfeeding was natural. Midwives stated it was different to care for women with ID and requested additional knowledge. The majority of midwives affirmed that women with ID could not manage the mother role satisfactorily, and one-third expressed that women with ID should refrain from having children. A majority of the midwives considered that the children should grow up with the parents with support from family and society, but one out of five stated that the children should grow up in foster care. Conclusion: Women with ID and their children should be considered as risk groups in pregnancy and childbirth. Professionals in maternity services need to elucidate their knowledge and skills for counselling and supporting this particular group of pregnant women in pre-, intra- and post-partum care.

Disability advocates in the twenty-first century have frowned upon the practice of institutionalization in disability services, yet many people with intellectual disability continue to be institutionalized in other settings such as correctional facilities. The prison system is a difficult environment for people with intellectual disability to negotiate, and they may find themselves victimized, segregated and isolated with very few resources to survive the experience. Incarceration may present a temporary solution to preventing anti-social behaviour in society. However, for offenders with intellectual disability, it often fails to address their criminal behaviour or the social context from which the behaviour emanates. Policy and practice in the disability service sector needs to develop further awareness of the needs of people with intellectual disability who come into contact with the criminal justice system as offenders. Similarly, correctional systems need to expand their knowledge base on the habilitative and rehabilitative needs of prisoners with intellectual disability in order to better address the issues that may arise from their incarceration. This exploratory qualitative study gathers the life stories of ten ex-prisoners from Queensland correctional facilities who have been labelled as having an intellectual disability by the service systems they have accessed. It utilizes an interpretive, social constructionist framework to understand people’s experiences. Life stories were gathered from in-depth interviews with participants over a prolonged period of time and supplemented by contextual information provided by six practitioners from disability, mental health and ex-prisoner services. The stories of three participants with intellectual disability were analysed through the holistic lens of a narrative approach and all ten stories were analysed thematically, providing an aggregate picture of all participants’ experiences. The findings of this thesis indicate that participants in this study had personal needs to belong, to feel competent and for others to see their criminal activity as an unfortunate but very human response to difficult circumstances. These needs were not always met within the prison environment and many participants struggled to feel safe in such a context. There were many pre-prison characteristics of participants that influenced their adaptation to prison, and they were also subjected to a series of degradations such as enforced isolation, frequent strip-searching, verbal and physical assault. However, these factors were not always constructed as negative or significant experiences by participants, and were often counterbalanced by perceived benefits to prison life such as friendship, food and reprieve from community living. These constructions of their experience highlight the vulnerability of this group within the prison environment and the failure of 2 the system and broader society to address core issues for people when they returned to the community. Significant disparities were also found between the philosophies of disability service support and the correctional enterprise. This study has indicated the urgent need for cross-agency collaboration in addressing the needs of people with intellectual disability. The thesis makes a contribution to both doing research with people with intellectual disability and to understanding their experiences of incarceration. The voices of people with intellectual disability have long been overlooked in research because it was assumed they could not express their views or because researchers did not have appropriate research approaches. It is only recently that some writers have captured the viewpoints of people with intellectual disability in academic discourse, but there has been little work done with prisoners and ex-prisoners with intellectual disability. Researching the experience of imprisonment with people with intellectual disabilities also presented unique ethical and methodological challenges. This thesis covers ethical issues such as informed consent, incriminating disclosure, self-determination and veracity and bias in life story research. It also develops knowledge in this area regarding recruitment, communication practices, and dissemination of findings. Overall, the study provides a nuanced account of life inside prison for people with intellectual disability. It makes a valuable contribution to the field of inclusive research with people with impaired capacity and to criminological research in this area.

People with an intellectual disability have high levels of sedentary behaviour (Temple, Frey, & Stanish, 2006) and health conditions associated with inactivity such as cardiovascular disease (Draheim, 2006) and obesity (Rimmer & Yamaki, 2006). Physical activity has been identified as one of the most successful strategies used to decrease these health risks. Four participants with an intellectual disability were recruited from the Special Olympics Athletic Club and participated in a 9-week strength and aerobic exercise program which consisted of a face-to-face program and an at-home component. During the face-to-face program participants took part in an aerobic warm up, strength training using exercise bands, skill development, and games. The strength skills were introduced progressively over the 9-weeks and were analyzed for mastery at the end of each face-to-face session using a procedural task analysis check list. Mastery was reached if participants completed a skill three consecutive times with no prompting. However, once a skill was completed with no more then visual prompting it was added to the at-home component of the program. At the end of each face-to-face session participants planned two additional days per week to exercise in their homes. The at-home component included an interactive exercise DVD that mirrored the strength and aerobics exercises introduced at the face-to-face program. Completion of the planned exercises was confirmed by self-report in log books and conversation with the researcher during prompting telephone calls. Pre and post tests for self-efficacy and a program satisfaction questionnaire were also conducted. Three participants reached mastery for biceps curls and one participant reached mastery for triceps extensions and back leg raises. Three participants completed all six strength exercises and one participant completed four exercise skills with no more than visual prompting. Participants required less prompting as the weeks progressed even with an increase in the number of skill components being tested. Adherence to the at-home component of the program for each participant was: 100%, 94%, 94%, and 28%. A dependent t-test revealed that self-efficacy toward exercise did not significantly increase from pre-test (M = 12.1) to post-test (M = 13.3) t (3) = 2.03, p = .14. These findings suggest that adults with an intellectual disability can acquire exercise band strength skills in a relatively short period of time and some participants are able to utilize these skills consistently at home. Participants in the current study failed to improve their self-efficacy toward exercise; however pre-test self-efficacy scores were quite high.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A presente pesquisa tem por objetivo implementar e avaliar um programa de inserção de jovens com deficiência intelectual em atividades laborais na Faculdade de Educação da Universidade do Estado do Rio de Janeiro.Para tal, foi utilizado o conceito de emprego customizado, que baseia-se na criação e/ou adaptação de postos de trabalho em empresas e outras instituições, se adequando a demanda do empregadorcom as habilidades do sujeito com deficiência, de forma a criar uma função que atenda às necessidades de ambas as partes. Um dos procedimentos da customização do trabalho é o Perfil Pessoal Positivo PPP, uma estratégia para traçar as habilidades e dificuldades dos jovens e adultos com deficiência, de forma a facilitar sua inserção no mercado de trabalho e outros espaços sociais. Participaram da pesquisa quatro jovens com deficiência intelectual, denominados treinandos indicados pelos professores de uma escola especial da rede pública do Estado do Rio de Janeiro, oriundos decursos de formação inicial e continuada em auxiliar de serviços gerais e auxiliar de contínuo-reprografia. Utilizou-se a metodologia de pesquisa-ação, com dados colhidos através de entrevistas semiestruturadas com os sujeitos com deficiência intelectual e os funcionários da Faculdade de Educação, assim como observação de seu desempenho. Como dados complementares, também foram realizadas entrevistas semiestruturadas com as mães dos jovens e os funcionários da Faculdade de Educação que aturaram diretamente com os treinandos. As entrevistas iniciais com os treinandos serviram como base para traçar seu o PPP, e determinar que atividades seriam mais adequadas para eles. Já as realizadas com os gestores da Faculdade, visaram compreender a dinâmica de funcionamento e as necessidades de trabalho da instituição.A elaboração do PPPpermitiu romperas barreiras impostas pelas exigências do mercado de trabalho, como escolarização mínima, capacitação, entre outras, pois, compreendendo as características do sujeito, é possível encontrar funções laborais que se adequem às suas singularidades e, ao mesmo tempo, atendam às necessidades do empregador. Concluímos, com base nos dados colhidos, que analisar o ambiente de trabalho com o objetivo de oferecer mão deobra adequada para a demanda é pré-requisito para a contratação e inclusão laboral de pessoas com deficiência. A customização do emprego contribui para a eliminação das barreiras atitudinais e preconceitos, aumentando as probabilidades de um desempenho e produção laboral satisfatória, beneficiando, tanto a instituição quanto o funcionário. / The present research has the objective of implement and evaluate a program that inserts young people with intellectual disabilities in work activities at the School of Education College of the Rio de Janeiro State University. For that, the concept of customized job was used, which is based on the creation/adaptation of work posts in companies and other institutions, meeting the demands of the employer with the skills of the handicap person, the forma that benefits both parties. One of the procedures of work customization is the Positive Personal Profile PPP, a strategy to trace the skills and difficulties people with disability have, in a way to facilitate their inclusion in the work market and other social spaces. Four youth with intellectual disability took part on the research, they were called trainees and were indicated by the teachers of a special school of the public network of Rio de Janeiro; they were graduates formation courses in general services (cleaning) and administrative helpers. The methodology used was the action research, with data collected from semi-structured interviews with the subjects and employees of the School of Education, as well as from the observation of their performance. Semi-structured interviews with the mothers of the subjects and with the employees of the Education College that had direct contact with the trainees, provided complementary data. The initial interviews with the trainees served as a foundation to trace their PPP, and determine the activities that would be more adequate for them. The interview with the supervisors from the College had the objective of understanding the functioning dynamic and the institutions work needs. The elaboration of the PPP allowed the break of some barriers of the work market, like minimal school graduation, capacitation, among others, because when you understand the characteristics of the subject you can find work functions that adapt to his uniqueness and at the same time fulfill the employers needs. We conclude, based on the data collected, that analyzing the work environment with the objective of offering proper workforce is prerequisite for laboral inclusion of deficient people. Job customization contributes for eliminating the barriers of attitude and prejudice, enhancing the probabilities of a satisfactory production and performance meeting both the institution and the employees needs.

Submitted by Leonardo Cavalcante (leo.ocavalcante@gmail.com) on 2018-04-23T22:50:06Z No. of bitstreams: 1 Arquivototal.pdf: 7015058 bytes, checksum: 0d8c1dd0bc2f42ab36a2d917f1dc6a05 (MD5) / Made available in DSpace on 2018-04-23T22:50:06Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 7015058 bytes, checksum: 0d8c1dd0bc2f42ab36a2d917f1dc6a05 (MD5) Previous issue date: 2015-07-06 / A part of the populations in Northeastern Brazil are relatively isolated geographically and these populations maintain the tradition of consanguineous marriages for generations. These two factors (isolation and inbreeding) increase the risk of birth of people with autosomal recessive intellectual disabilities. The objective of this study was to determine the genetic causes of intellectual disabilities in two large consanguineous families of Paraiba backlands. In 2012, we conducted an epidemiological study to investigate the contribution of genetic factors in determining the deficiencies in six municipalities of Paraíba previously selected by presenting high consanguinity rate. Families who had patients with neurodegenerative disorders and/or intellectual disabilities (ID) were invited by community health agents for a first screening realized by biologists in order to select patients with deficiency probably caused by genetic mutations. In total, 276 patients were screened, of which, 109 were selected for medical evaluation with neurologists. After medical evaluation, two families with multiple affected individuals in two different forms of autosomal recessive intellectual disability were selected for clinical and genetic research. We performed the linkage study using SNPs array analysis to determine homozygous regions. Subsequently, the whole exome sequencing (WES) of one affected individual of each family was sequenciated. Potentially deleterious variants detected in regions of homozigosity-by descent which were not present in Brazilian population controls or in exomes of global online databases were subject to further scrutiny and segregation analysis by Sanger sequencing. Family A has seven adult siblings with syndromic ID. Phenotype includes tall forehead, prognatism, prominent chin, very large and overhanging nose tip. Homozigosity-by-descent analysis found a 4.0 Mb region in 19q13.32-q13.33 (lod score: 3.24). WES disclosed a homozygous variant (c.418C>T, p.Arg140Trp) in mediator complex subunit 25 (MED25), predicted as deleterious by Provean, Mutation Taster, PolyPhen-2 and SIFT. MED25 is a component of the Mediator complex, involved in regulation of transcription of nearly all RNA polymerase II-dependent genes. Deleterious mutations in MED12, MED17, MED23 and recently after our publication another mutation in the MED25 have been associated with ID. Family B has nine affected adults descending from four closely related first-cousin couples affected by severe non-syndromic ID. Homozigosity-by-descent analysis disclosed a 20.7 Mb region in 8q12.3-q21.2 (lod score: 3.11). WES identified a homozygous deleterious variant in inositol monophosphatase1 gene (IMPA1), consisting of a 5 bp duplication (c.489_493dupGGGCT) leading to frameshift (p.Ser165Trpfs*10). IMPA1 gene product is responsible for the final step of biotransformation of inositol triphosphate and diacylglycerol, two second messengers, and up to now, despite its many physiological functions, no clinical phenotype has been assigned to this gene dysfunction. From this study, it was possible to develop diagnostic test by restriction enzyme and therapeutic perspective for cases associated with IMPA1. / Uma parte das populações do Nordeste brasileiro está relativamente isolada geograficamente e mantêm, há várias gerações, a tradição de casamentos consanguíneos. Esses dois fatores associados (isolamento e endocruzamento) elevam o risco de nascimento de pessoas com deficiência intelectual com herança genética autossômica recessiva. O objetivo deste trabalho foi determinar as causas genéticas da deficiência intelectual em duas grandes famílias consanguíneas do sertão paraibano. Em 2012, nosso grupo de pesquisa realizou um estudo epidemiológico para determinar a contribuição de fatores genéticos na determinação das deficiências em seis municípios do sertão paraibano selecionados previamente por apresentarem elevada taxa de consanguinidade. As famílias que apresentavam repetições de indivíduos com doenças neurodegenerativas e/ou deficiência intelectual (DI) foram convocadas pelos agentes comunitários de saúde para uma primeira triagem, realizada pelos biólogos geneticistas, a fim de selecionar pacientes que apresentavam deficiência por prováveis causas genéticas. No total, foram triados 276 pacientes, sendo que, 109 foram selecionados para avaliação médica com neurologistas. Após a avaliação médica, duas famílias com múltiplos indivíduos acometidos por duas diferentes formas de DI de herança autossômica recessiva foram selecionadas para investigação clínico-genética. O estudo de ligação para determinar regiões em homozigose foi realizado com o uso da técnica de array de SNPs. Posteriormente, foi feito o sequenciamento do exoma completo de um indivíduo afetado de cada família. Variantes potencialmente deletérias detectadas em regiões em homozigose e que não estavam presentes em controles brasileiros e em banco de dados mundiais, foram objetos de uma análise mais aprofundada e feito a análise de co-segregação através do sequenciamento de Sanger. A primeira família estudada, a família A, possui sete adultos com DI sindrômica. O fenótipo inclui testa alta, prognatismo, queixo proeminente e ponta do nariz saliente, além da DI grave. O estudo de ligação apontou duas regiões com LOD scores máximos = 3,234, uma região de 26 Mb no cromossomo 2 (2p12 - q11.2) e uma região de 4,0 Mb no cromossomo 19 (19q13.32 - q13.33). O sequenciamento do exoma revelou uma variante em homozigose (c.418C>T, p.Arg140Trp) no gene MED25 (subunidade 25 do complexo mediador), predita como deletéria por diferentes softwares (Polyphen, Provean, Mutation Taster e SIFT). O complexo mediador está envolvido na regulação da transcrição de quase todos os genes dependentes da RNA polimerase II. Mutações deletérias nos genes MED12, MED17, MED23 e, recentemente, outra mutação no MED25, têm sido associadas com DI. Já a segunda família estudada, a família B, possui nove adultos afetados, descendentes de quatro relações consanguíneas entre primos de primeiro grau, com DI grave não-sindrômica. O estudo de ligação apontou uma região de 20,7 Mb no cromossomo 8 (8q12.3-q21.2) com LOD score = 3,11. O sequenciamento do exoma identificou uma variante deletéria em homozigose no gene inositol monofosfatase1 (IMPA1), que consiste em uma duplicação de 5 pares de bases (c.489_483dupGGGCT), levando a uma mutação do tipo frameshift (p.Ser165Trpfs*10). O produto do gene IMPA1 é uma enzima responsável pela etapa final da biotransformação dos segundos mensageiros inositol trifosfato e diacilglicerol, e até o momento, apesar de apresentar importantes funções fisiológicas, não havia fenótipo clínico atribuído a esse gene. A partir deste estudo, foi possível desenvolver teste diagnóstico com triagem por enzima de restrição e perspectiva de tratamento terapêutico para os casos associados ao IMPA1.

Submitted by Isabel Augusta Fogaça De Almeida (isabel.fogaca@yahoo.com.br) on 2018-11-14T20:21:08Z No. of bitstreams: 1 TRABALHOFINALIZADO1.pdf: 1839654 bytes, checksum: eeecee66deb3f73247649c61e70cdc97 (MD5) / Approved for entry into archive by Jacqueline de Almeida null (jacquie@franca.unesp.br) on 2018-11-21T14:54:52Z (GMT) No. of bitstreams: 1 Almeida_IAF_me_fran.pdf: 1839654 bytes, checksum: eeecee66deb3f73247649c61e70cdc97 (MD5) / Made available in DSpace on 2018-11-21T14:54:52Z (GMT). No. of bitstreams: 1 Almeida_IAF_me_fran.pdf: 1839654 bytes, checksum: eeecee66deb3f73247649c61e70cdc97 (MD5) Previous issue date: 2018-08-30 / A deficiência intelectual (DI) é um conceito construído pela sociedade diante de seus valores histórico-sociais. Em consequência, a inclusão da pessoa com DI é algo que está sendo estruturado cotidianamente e as interpretações sobre o que é inclusão variam de acordo com a cultura e com o contexto social. Neste cenário, as leis e os decretos brasileiros modificam-se para que o direito de acesso à escola seja comum a todos os seres humanos, porém, sabe-se que são necessárias políticas públicas para que a legislação seja efetiva diante dos desafios do modelo arcaico escolar. O principal objetivo deste trabalho é investigar a produção científica e/ou acadêmica sobre inclusão de pessoas com deficiência intelectual no ensino regular, tendo como metodologia o Estado da Arte ou do Conhecimento nas pesquisas apresentadas na Plataforma SCIELO e LILACS entre 1994 e 2017, utilizando os seguintes descritores: inclusão da pessoa com deficiência intelectual, inclusão do aluno com deficiência intelectual, deficiência intelectual e inclusão, deficiência intelectual na escola. Por meio dos trabalhos encontrados, foi possível identificar que cinco pilares são necessários para sustentar e efetivar a inclusão do aluno com DI, a reestruturação da escola, a capacitação dos professores, o apoio teórico das universidades, a elaboração de políticas públicas e o trabalho pedagógico inovador. / The intellectual disability is a concept built for society in view of their historical-social values. As a consequence, the inclusion of the person with ID is something that is being structured daily, and the interpretations about what is included vary according to the culture and the social context. In this scenario, Brazilian laws and decrees are modified so that the right of access to the school is common to all human beings, but it is known that public policies are necessary to make legislation effective in the face of the challenges of the archaic model school. The main objective of this work is to investigate the scientific and / or academic production on the inclusion of people with intellectual disabilities in regular education using as methodology the State of Art or Knowledge in the research presented in the SCIELO and LILACS Platform between 1994 and 2017, using the following descriptors: inclusion of the person with intellectual disability, inclusion of the student with intellectual disability, intellectual disability and inclusion, intellectual disability in school. Through the works found, it was possible to identify that five pillars are necessary to sustain and to effect the inclusion of the student with ID, the restructuring of the school, the training of the teachers, theoretical support of the universities, elaboration of public policies and innovative pedagogical work.

Eukaryotic Elongation Factor 1A (eEF1A) plays a key role in protein synthesis by delivering aminoacylated tRNAs to the A site of the ribosome. In higher vertebrates, two isoforms of eEF1A exist called eEF1A1 and eEF1A2, with eEF1A2 being expressed in adult brain, heart and skeletal muscle. Since 2012, several different de novo heterozygous missense mutations in EEF1A2 have been identified in humans and these cause epilepsy, intellectual disability and autism. Before considering treatment options, it is vital to determine whether these mutations cause loss or gain of protein function. I performed a battery of behavioural tests using two mouse lines with heterozygous loss of function mutations in eEF1A2. The aim was to determine whether there were any behavioural phenotypes consistent with intellectual disability and/or autism. Using heterozygous wasted mice (Eef1a2+/wst), I analysed the effects of aging on behaviour and found that Eef1a2+/wst mice showed reduced marble burying activity and reduced movement in the open field test with age. In a test of social behaviour, Eef1a2+/wst mice showed a significantly reduced preference for social novelty at all ages tested. The second heterozygous null line, Del22.ex3, was generated on a pure C57BL/6J genetic background. This new line was made in order to reduce the level of variation observed in data from the wasted line, which was on a mixed genetic background. The genetic background was shown to have an influence on behaviour as the results differed between this line and the wasted line. Del22.ex3 Eef1a2+/- mice showed significantly reduced engagement in repetitive behaviours compared with wild-type littermates and normal preference for social novelty. Using CRISPR/Cas9, a mouse line with the D252H missense mutation was generated and I repeated my behavioural testing on heterozygotes from this line. I found no behavioural abnormalities in this line suggesting a mouse-human difference in the ability to tolerate eEF1A2 missense mutations. Previous attempts to make a line with the G70S missense mutation were unsuccessful but as a product of this experiment, it was found that mice expressing G70S eEF1A2 had a comparable phenotype to and died at the same age as complete knockouts. This suggested that the G70S protein is non-functional and cannot compensate for loss of wild-type eEF1A2. These experiments have improved our understanding of the phenotypic effects of Eef1a2 mutations in mice and have shown, for the first time, that mutations in Eef1a2 affect mouse behaviour.

Intellectual disability (ID) and autism spectrum disorders (ASDs) can have a devastating impact on an individual’s functioning and quality of life. Insights from pre-clinical models of monogenic forms of ID and ASD are now revealing the biochemical pathways and aberrations in cellular and synaptic functioning involved. One monogenic cause of ID, ASD and epilepsy is SYNGAP1 ID which results from mutations in the SYNGAP1 gene on human chromosome 6. Although a variety of symptoms have been reported, many affected individuals have moderate to severe intellectual impairment and severe seizure phenotypes. Previous pre-clinical studies have mainly focussed on the effects of altered SynGAP expression in mice. This thesis is therefore the first to explore altered SynGAP expression in a rat model. It also adds to the body of research exploring the roles of SynGAP isoforms in glutamatergic synaptic function. The SynGAP_GAP deletion rat was engineered to have a deletion encompassing the enzymatically active GTPase activating protein (GAP) domain of the protein, via which SynGAP regulates multiple biochemical pathways by enhancing the slow intrinsic hydrolysis of GTP by GTP-binding proteins. SyngapGAP/GAP rats appeared small and failed to thrive. As with Syngap-/- mice, this complete loss of WT SynGAP proved lethal, whereas Syngap+/GAP rats appeared to develop normally. The electrophysiological data obtained from this new model reveals a reduction in the frequency of miniature excitatory post-synaptic currents (mEPSCs) in Syngap+/GAP cultured neurons. However the exaggerated hippocampal long-term depression identified in Syngap+/- mice was not seen in the rats. There was also no evidence of differences in intrinsic cell properties, excitatory and inhibitory currents or ratios of AMPAR / GABAAR and AMPAR / NMDAR between WT and heterozygous rats. In addition to the characterisation of the SynGAP_GAP deletion rat, the impact of the previously unstudied Eα1 isoform on forebrain neuronal synaptic function was examined through mEPSC recordings. A trend towards lower mEPSC frequency was found which supports previous research showing that α1 isoforms reduce synaptic strength. This body of work therefore adds to published evidence of isoform specific functions and provides the first evidence of the impact of SynGAP alterations in rats, the results of which show some intriguing differences from previous work in mice.

Submitted by Lucienne Costa (lucienneferreira@ufcg.edu.br) on 2018-08-29T16:29:31Z No. of bitstreams: 1 LAÍS VENÂNCIO DE MELO – DISSERTAÇÃO (PPGED) 2018.pdf: 4862301 bytes, checksum: db824cf9c3511a18ab9371ca564db742 (MD5) / Made available in DSpace on 2018-08-29T16:29:31Z (GMT). No. of bitstreams: 1 LAÍS VENÂNCIO DE MELO – DISSERTAÇÃO (PPGED) 2018.pdf: 4862301 bytes, checksum: db824cf9c3511a18ab9371ca564db742 (MD5) Previous issue date: 2018-04-18 / O direito público subjetivo à educação se encontra positivado no ordenamento jurídico brasileiro, mas ainda enfrenta limites quanto à sua incorporação nas práticas sociais escolares. Barreiras arquitetônicas, comunicacionais e, sobretudo, atitudinais causam prejuízos em relação ao acesso e à permanência na escola, com apropriação dos saberes escolares, por parte do coletivo dos indivíduos em situação de deficiência. Nesse contexto, a análise da dimensão subjetiva da educação assume posição relevante, o que justifica esta pesquisa, de caráter qualitativo e matriz sócio-histórica. O objetivo geral foi analisar as concepções de professores do Atendimento Educacional Especializado (AEE) acerca da deficiência e da deficiência intelectual e suas implicações para a mediação pedagógica em contexto de ensino-aprendizagem do AEE. Além dos docentes, participaram da pesquisa sujeitos em atendimento no AEE e seus responsáveis. Os instrumentos foram questionários, entrevistas semiestruturadas e observações participantes de sessões do AEE, cujos dados foram analisados sob perspectivas de pedagogias crítico-dialéticas. A partir da análise dos dados, constatamos a hibridização de paradigmas sobre a deficiência, com forte presença de aspectos da privação cultural, e o frágil conhecimento sobre a deficiência intelectual, configurado majoritariamente pelos saberes de experiência, os quais influenciam na produção dos tipos de mediação evasiva e coercitiva. Com menor incidência, observamos o paradigma da construção social e a definição da deficiência intelectual com melhor conceituação, que interferem na construção do tipo de mediação exitosa e qualificada nas interações sociais do AEE. As implicações pedagógicas da pesquisa apontam para a necessidade de produção de políticas de formação docente melhor qualificada, que tematizem as concepções de deficiência e de deficiência intelectual e o desenvolvimento cognitivo dos indivíduos em situação de deficiência intelectual, e que ressaltem os modos pelos quais as concepções e mediações docentes escolares impactam a sua constituição intersubjetiva, intensificando a reprodução escolar da ideologia da deficiência/normalidade ou problematizando-a, com a contribuição da escola e dos docentes enquanto agentes sociais imprescindíveis à construção do modelo includente escolar em sociedades desiguais. / The subjective public right to education is in the Brazilian legal system, but still faces limits on its incorporation into school social practices. The architectural, communication and, above all, the attitudinal barriers cause damages in relation to access and permanence in school, with the appropriation of the school knowledge, by the individuals in situation of disability. In this context, the analysis of the subjective dimension of education assumes a relevant position, which justifies this qualitative and socio-historical approach. The general objective was to analyze the conceptions of teachers of the Specialized Educational Assistance (AEE) about the disability and the intellectual disability and its implications for pedagogical mediation in the teaching-learning context of AEE. These teachers, the students and their parents were the subjects of our research. The instruments were questionnaires, semi-structured interviews and participant observations from AEE sessions, whose information were analyzed under perspectives of critical-dialectical pedagogies. Based on data analysis, we have observed the hybridization of paradigms on disability, with a strong presence of aspects of cultural deprivation, and the fragile knowledge about intellectual deficiency, configured mainly by experiential knowledge, which influence the production of types of mediation evasive and coercive. The paradigm of social construction and the definition of intellectual disability by the difficulties in the triad of cognitive functioning, adaptive behavior and social aspects, which arise with less incidence and interfere in the construction of the type of successful and qualified mediation in the social interactions of AEE. The pedagogical implications of the research point to the need to produce better qualified teacher education policies that focus on the conceptions of disability and intellectual disability and the cognitive development of ISDI, and which highlight the ways in which teacher conceptions and mediations impact the intersubjective constitution of the subjects, intensifying the school reproduction of the ideology of the deficiency/normality or problematizing it, with the contribution of the school and the teachers as social agents essential to the construction of the school model in unequal societies.