An accurate diagnosis of schizophrenia is difficult; no reliable biomarkers of the disease exist. We present a computational approach for diagnosis of schizophrenia from electroencephalography (EEG) recordings. Novel and existing mathematical methods for the interpretation of EEG are surveyed and compared. Methods utilizing single electrodes are used in conjunction with those incorporating the recordings of multiple electrodes. A data-driven, machine-learning approach is used to automate the selection of relevant features, which are then classified using least-squares support vector machines. This approach yielded a prediction accuracy of 86.5%, using a stringent application of correct statistical techniques. Those features deemed most relevant are related with known abnormalities symptomatic of schizophrenia.

An accurate diagnosis of schizophrenia is difficult; no reliable biomarkers of the disease exist. We present a computational approach for diagnosis of schizophrenia from electroencephalography (EEG) recordings. Novel and existing mathematical methods for the interpretation of EEG are surveyed and compared. Methods utilizing single electrodes are used in conjunction with those incorporating the recordings of multiple electrodes. A data-driven, machine-learning approach is used to automate the selection of relevant features, which are then classified using least-squares support vector machines. This approach yielded a prediction accuracy of 86.5%, using a stringent application of correct statistical techniques. Those features deemed most relevant are related with known abnormalities symptomatic of schizophrenia.

Discovery of a new host-parasite relationship, <i>Parelaphostrongylus odocoilei</i> in Dalls sheep (<i>Ovis dalli dalli</i>) in the Canadian North, prompted the first investigation of the geographic distribution, pathogenesis, ecology and epidemiology of this parasite, as well as the related protostrongylid <i>Protostrongylus stilesi</i>, at Subarctic latitudes (60-65ºN). All protostrongylid parasites have an indirect life-cycle, where first-stage larvae are shed in the feces of a mammalian definitive host, penetrate the foot of a gastropod intermediate host, and develop to infective third-stage larvae. <p> Protostrongylid larvae were recovered from over 2000 fecal samples from thinhorn sheep (<i>Ovis dalli</i>) and other hosts for <i>P. odocoilei</i> and <i>P. stilesi</i> across northwestern North America (38-69 ºN). Through novel application of molecular techniques to identify morphologically indistinguishable first-stage larvae, new records for <i>P. odocoilei</i> were established at 20 locations. This provided insight into the historical origins and biogeography of this new host-parasite relationship, and greatly expanded the known geographic range of both protostrongylids. <p> Clinical effects, including a neurological syndrome, were described in five thinhorn sheep experimentally infected with <i>P. odocoilei</i>. Neural and respiratory pathology in these five sheep were compared with over 50 wild Dalls sheep from a population naturally infected with <i>P. odocoilei</i> and <i>P. stilesi</i>. In the end stages, diffuse verminous interstitial pneumonia associated with P. odocoilei led to respiratory failure, and may have acted as a predisposing factor for bacterial pneumonia, which caused sporadic mortalities in this wild population. <p> At Subarctic latitudes, seasonal patterns in host and parasite availability, including larval shedding by Dalls sheep and larval development in experimentally infected gastropods, suggested that lambs become infected with <i>P. odocoilei</i> in a narrow seasonal window in their first fall on winter range. In combination with laboratory experiments, a degree day model for temperature-dependent larval development was developed, validated, and applied to describe and predict the effects of climate warming on protostrongylid parasites of thinhorn sheep in northern North America. In a future of climate warming, the narrow seasonal window for parasite development and transmission would be significantly extended, leading to amplification of populations of <i>P. odocoilei</i> and <i>P. stilesi</i> in endemic regions, and possibly range expansion of <i>P. odocoilei</i>. This may have consequences for the health of thinhorn sheep, as well as other wildlife that are important resources in the Canadian North.

Discovery of a new host-parasite relationship, <i>Parelaphostrongylus odocoilei</i> in Dalls sheep (<i>Ovis dalli dalli</i>) in the Canadian North, prompted the first investigation of the geographic distribution, pathogenesis, ecology and epidemiology of this parasite, as well as the related protostrongylid <i>Protostrongylus stilesi</i>, at Subarctic latitudes (60-65ºN). All protostrongylid parasites have an indirect life-cycle, where first-stage larvae are shed in the feces of a mammalian definitive host, penetrate the foot of a gastropod intermediate host, and develop to infective third-stage larvae. <p> Protostrongylid larvae were recovered from over 2000 fecal samples from thinhorn sheep (<i>Ovis dalli</i>) and other hosts for <i>P. odocoilei</i> and <i>P. stilesi</i> across northwestern North America (38-69 ºN). Through novel application of molecular techniques to identify morphologically indistinguishable first-stage larvae, new records for <i>P. odocoilei</i> were established at 20 locations. This provided insight into the historical origins and biogeography of this new host-parasite relationship, and greatly expanded the known geographic range of both protostrongylids. <p> Clinical effects, including a neurological syndrome, were described in five thinhorn sheep experimentally infected with <i>P. odocoilei</i>. Neural and respiratory pathology in these five sheep were compared with over 50 wild Dalls sheep from a population naturally infected with <i>P. odocoilei</i> and <i>P. stilesi</i>. In the end stages, diffuse verminous interstitial pneumonia associated with P. odocoilei led to respiratory failure, and may have acted as a predisposing factor for bacterial pneumonia, which caused sporadic mortalities in this wild population. <p> At Subarctic latitudes, seasonal patterns in host and parasite availability, including larval shedding by Dalls sheep and larval development in experimentally infected gastropods, suggested that lambs become infected with <i>P. odocoilei</i> in a narrow seasonal window in their first fall on winter range. In combination with laboratory experiments, a degree day model for temperature-dependent larval development was developed, validated, and applied to describe and predict the effects of climate warming on protostrongylid parasites of thinhorn sheep in northern North America. In a future of climate warming, the narrow seasonal window for parasite development and transmission would be significantly extended, leading to amplification of populations of <i>P. odocoilei</i> and <i>P. stilesi</i> in endemic regions, and possibly range expansion of <i>P. odocoilei</i>. This may have consequences for the health of thinhorn sheep, as well as other wildlife that are important resources in the Canadian North.

Alternative splicing (AS) is a major source of biological diversity and a crucial determinant of cell fate and identity. Characterizing the role of AS regulatory networks in physiological and pathological processes remains challenging. The work presented here addresses this challenge using systems biology analyses of AS regulatory networks in programmed cell death and neurological disorders. The first study describes a genome-wide screen based on splicing-sensitive reporters to identify factors that affect the AS of apoptosis regulators Bclx and Mcl1. The screen identified over 150 factors that affect apoptosis through modulating the pro- and anti-apoptotic splicing variants of these apoptosis regulators. This screen revealed a new functional connection between apoptosis regulation and cell-cycle control through an AS network. It also unearthed many disease-associated factors as AS effectors. The second study describes the functions of the Polyglutamine-binding protein 1 (PQBP1)-mediated AS regulatory network in neurological disorders. PQBP1 is a factor linked to intellectual disability and was unexpectedly identified as an AS effector from the screen described above. We found that PQBP1 influences the splicing of many mRNAs and is associated with a wide range of splicing factors. Depletion of PQBP1 in mouse primary cortical neurons caused defects in neurite outgrowth and altered AS of mRNAs enriched for functions in neuron projection regulation. Disease-mutants of PQBP1 lose associations with splicing factors and cannot complement the aberrant AS patterns and neuron morphology defects in PQBP1 depleted-neurons. This study revealed a novel function of PQBP1 in AS regulation associated with neurite outgrowth and indicated that aberrant AS underlies the pathology of PQBP1-related neurological disorders. A final study examines the dynamics of the Drosophila Sex-lethal AS regulation network using a combination of experimental tools and mathematical modeling. This study demonstrates that the features of Sxl AS regulation have great potentials in building synthetic memory circuits in mammalian cells to track cell fate. Collectively, this work describes the landscape of three diverse AS regulatory networks in various biological processes. The results and methods presented here contribute to our rapidly advancing knowledge of AS regulation in biology and human disease.

Les neurones exprimant l'hormone de mélano-concentration (MCH) sont observés dans l'hypothalamus postérieur de tous les vertébrés, de la lamproie à l'Homme. Ces neurones sont impliqués dans diverses fonctions comme le cycle veille/sommeil ou la prise alimentaire. Ils forment une population non homogène et au moins deux sous-populations sont reconnues, chez le rat. La première sous-population est composée de neurones nés au 11ème jour de vie embryonnaire (E11) qui projettent massivement sur les régions les plus postérieures du système nerveux central. La seconde est générée à E12/E13 et les neurones la caractérisant projettent sur les régions les plus antérieures du cerveau et expriment le peptide CART (cocaine and amphetamine regulated transcript) et le récepteur NK3 (neurokinine). L'objectif de notre travail était de comprendre l'origine de ces deux sous-populations. Pour cela, nous avons utilisé des approches histologiques, moléculaires et in vitro. Les neurones à MCH sont parmi les premiers neurones à naître et à différencier leur phénotype chimique le long d'une région longitudinale définie par une prolifération intense, appelée " cell cords " par Keyser en 1972. Cette bande longitudinale est caractérisée par l'expression de gènes comme Sonic Hedgehog (Shh), Nkx2.1, Nkx2.2 et a été récemment renommée " diagonale intrahypothalamica " ou ID. La différenciation des neurones à MCH dépend de l'expression du facteur morphogène Shh et ces neurones expriment Nkx2.1 et Nkx2.2, facteurs de transcription régulés positivement par Shh. Les neurones de la première sous-population envoient des projections le long du premier tractus longitudinal à se mettre en place, le tractus postopticus (tpoc). Ceux issus de la deuxième sous-population se différencient concomitamment au développement des régions télencéphaliques et leurs projections changent de direction pour innerver les régions antérieures du cerveau sous la dépendance de protéines de guidage axonal, Nétrine1 et Slit2. Nétrine1 permet d'attirer les axones MCH exprimant le récepteur DCC précocement vers la moelle épinière et plus tardivement vers le télencéphale alors que Slit2 contraint les axones MCH exprimant Robo2 à sortir de l'hypothalamus. L'étude du modèle " MCH " permet de mettre en lumière un changement d'organisation précocement au cours du développement dans l'axe longitudinal du prosencéphale. La bande longitudinale d'expression des facteurs de transcription Shh, Nkx2.2 peut être perçue comme une extension rostrale de la colonne neurogénique médiane déjà décrite chez des espèces d'invertébrés possédant une symétrie bilatérale. Les neurones générés le long de cette colonne le sont très tôt au cours du développement. / Neurons expressing melanin-concentrating hormone (MCH) are observed in the vertebrate posterior hypothalamus, from lampreys to humans. These neurons are involved in various functions such as sleep/wake cycle or food intake. They form a non-homogeneous population and at least two sub-populations are indentified in the rat. The first sub-population is composed of neurons born on the 11th embryonic day (E11) that project heavily on posterior regions of the central nervous system. The second is characterized by neurons born at E12/E13, projecting in anterior regions of the brain and expressing the peptide CART (cocaine and amphetamine Regulated Transcript) and the NK 3 receptor (neurokinin). The aim of this study was to understand the origin of these two sub-populations. For this, we used histological, molecular and in vitro approaches. MCH neurons are among the first neurons to be born and to differentiate their chemical phenotype along a longitudinal region defined by intense proliferation and called " cell cord " by Keyser in 1972. This longitudinal band is characterized by the expression of genes such as Sonic Hedgehog (Shh), Nkx2.1, Nkx2.2 and was recently named " diagonal intrahypothalamica " or ID. Differenciation of MCH neurons depends on expression of the morphogenetic factor Shh and these neurons express Nkx2.1 and Nkx2.2, transcription factors upregulated by Shh. The neurons of the first sub-population send projections along the tractus postopticus (tpoc), which is the first longitudinal tract to develop. Neurons of the second sub-population differentiate concomitantly to the development of the basal forebrain and their projections innervate anterior brain regions. Our results obtained in vitro showed that Netrin1 attracts MCH axons and that this reponse is mediated by DCC. Slit2 repulses MCH axons and this reponse is mediated by the Robo2 receptor. Overall, our study of the development of the MCH system shed light on an organizational change in the longitudinal axis of the forebrain during early development : a primary longitudinal organization characterized by the longitudinal expression of Shh and Nkx2.2 and the path of the tractus postopticus in the diencephalon and mesencephalon. MCH neurons of the first sub-population develop during this stage. Then, as the basal telencephalon extends and expresses Netrin1, the medial forebrain bundle differentiates, inducing a change in the main axis of the forebrain ; meanwhile MCH neurons of the second sub-population appear. MCH sub-populations reflect distinct developmental stages of the forebrain.

The research, on which this account is based, took place within the context of Blooming Acres, my home, and the learning community that I co-founded with my wife Sherri-Ann. In the first chapters, I tell the story of how I came to home-educate learners with complex special needs at my farm north of Toronto, Canada. I describe the neurological disorders that the children in my care are diagnosed with and map out the main literature that guides how I think about and practice education. The aim of this section is to paint a picture of the context in which the research takes place and describe my role in this community. The second section consists of my research with two of the children who lived and learned at Blooming Acres. This includes their stories as told by them, their parent(s), and the educators at Blooming Acres. As I juxtaposed the life experiences of these learners with each other, and wove together aspects of these stories, significant themes emerged relating to their academic and medical histories, as well as their social, extracurricular, and family life, and finally, their experience at Blooming Acres. I employed a life history methodology; one that honours the meaning and knowledge that exists in the storied lives of individuals. As I applied this methodology and engaged in the storied lives of these learners I learned more about what it is like to live and learn with neurological disorders. Four major themes emerged. The first, Pathology for Support / Support for Pathology, relates to learning issues, referral, assessment, diagnosis, medications and “school battles”. Second, Parent Stress includes behavioural issues, judgment, stressful calls from teachers and principals and school failure. Third, Oasis Teachers / Mentors is an expression of care, support, social competence, self-esteem and relationships. Finally, Strengths and Coping is a culmination of issues such as advocacy for support, strategies for success, identifying and coping with stress, understanding diagnosis and becoming well. These emergent themes are articulated within the context of neurology and school failure (risk) and the context of transformation and getting well (resilience). This work contributes to parenting, education, social work, disabilities, medical and risk / resiliency literature.

Made available in DSpace on 2016-06-02T20:18:13Z (GMT). No. of bitstreams: 1 3415.pdf: 1250906 bytes, checksum: ba6707324e714954f634130cba45f223 (MD5) Previous issue date: 2010-11-12 / Universidade Federal de Minas Gerais / The palmar grasp behavior in human infants has been approached by this work. Three studies were conducted. The first study consisted of exposing the state of the art regarding the use of palmar grasp reflex (PGR) in neuropsichomotor assessment instruments and the use of PGR as a research subject in infants. The second study determined the reliability of an instrument to measure grasp strength in infants from birth to two months old. We have studied 39 healthy infants of both sexes who were allocated into three groups ("SC", "FR", "BL") according to the city from where came from . The equipment under test was called M-FLEX , which provides values of maximum grasp strength (FMAX), mean grip force (FMEAN) and grasp time (GT). The third study aimed to characterize the palmar grasp behavior of human infants , we studied 90 healthy infants of both sexes, born at term, originated from three Brazilian cities with climate and socio-cultural characteristics similars. Infants were classified into three groups according to their age. Measurements were performed on both hands face to the right side, face in the middle line and face to the left side. The variables were compared between sexes and correlated with data weight and height development. Comparisons were made of variables between the different positions of the face and between age groups. It was found that the side that the face is turned and age group are factors that affect the variables measured by M-FLEX and it is possible to measure how much asymmetry is tolerable to characterize the behavior of an infant with typical grasp. / O comportamento de preensão palmar em lactentes humanos foi abordado por este trabalho. Foram realizados 3 estudos. O estudo 1 consistiu em expor o estado da arte referente a utilização do reflexo de preensão palmar (RPP) nos instrumentos de avaliação neuropsicomotora e a utilização do RPP como objeto de pesquisa em lactente. O estudo 2 determinou a confiabilidade de um instrumento para medir a força de preensão palmar em lactentes, do nascimento aos quatro meses de idade. Foram avaliados 39 lactentes saudáveis, de ambos os sexos, compreendidos na faixa etária do nascimento aos quatro meses de vida que foram alocados em três grupos ( SC , FR , BL ) de acordo com a cidade de onde eram oriundos. O equipamento em teste denomina-se M-FLEX® o qual fornece valores de força de preensão máxima (FMAX), força de preensão média (FMED) e o tempo de preensão (TPR). O estudo 3 teve como objetivo caracterizar o comportamento de preensão palmar em lactentes humanos, para isso, foram estudados 90 lactentes saudáveis, de ambos os sexos, nascidos a termo, originados de três cidades brasileiras com características climáticas e sócio-culturais semelhantes. Os lactentes foram classificados em 3 grupos de acordo com a sua faixa etária. Foram realizadas medidas em ambas as mãos com a face voltada para o lado direito, com a face na linha média e com a face voltada para o lado esquerdo. As variáveis foram comparadas entre os sexos e correlacionadas com os dados pônderoestaturais. Foram feitas comparações das variáveis entre as diferentes posições da face e entre os grupos etários. Constatou-se que o lado que a face está virada e o grupo etário são fatores que interferem nas variáveis medidas pelo M-FLEX® e que é possível medir quanta assimetria é tolerável para caracterizar um lactente com comportamento de preensão palmar típico.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A retrospective study including dogs with neurological disease was conducted at the Service of Neurology (SN) of the Veterinary Teaching Hospital, Universidade Federal de Santa Maria (UFSM) between 2006 and 2013, with the objective to identify and characterize the age, breed and sex, neurological diseases and classify them according to the anatomical region and DINAMIT-V acronym. Were evaluated 1.277 neurological records of dogs and obtained the information for inclusion in the study in 1.184 of them being the etiological diagnosis in 525 (44,4%) and presumptive in 659 dogs (55,6%). The most common breeds were dachshunds (27,5%), followed by mixed breed. The most common sites were the spinal cord between T3-L3 (40,9%) and thalamus-cortex (17,5%). Most dogs were diagnosed with degenerative disorders (49%), being disc disease intervertebral more observed, followed inflammatory/infectious disease (16,6%). It can be concluded that the higher prevalence of neurological disorders in dogs involve the spinal cord and thalamus-cortex, with the most frequent being degenerative and the data obtained may assist future studies associated with frequency and distribution of the main neurological diseases in dogs. / Foi realizado um estudo retrospectivo de cães atendidos no Serviço de Neurologia (SN) do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria (UFSM), entre 2006 e 2013, com o objetivo de identificar e caracterizar a idade, raça e sexo, as doenças neurológicas e classificá-las de acordo com a região anatômica e acrônimo DINAMIT-V. Foram avaliadas 1.277 fichas neurológicas de cães e obtidas as informações para inclusão no estudo em 1.184 delas, sendo o diagnóstico etiológico confirmado em 525 cães (44,4%) e presuntivo em 659 (55,6%). As raças mais frequentes foram dachshunds (29,2%), seguido das sem raça definida. Os locais mais comuns foram a medula espinhal entre T3-L3 (40,9%) e tálamo-córtex (17,5%). A maioria dos cães foram diagnosticados com doenças degenerativas (49%) , sendo a doença do disco intervertebral a mais observada, seguido das doenças inflamatórias/infecciosas (16,6%). Pode-se concluir que a maior prevalência das doenças neurológicas de cães envolvem a medula espinhal e tálamo-cortex, sendo as degenerativas as mais frequentes e os dados obtidos poderão auxiliar em futuros estudos sobre a frequência e distribuição das principais doenças neurológicas em cães.

Made available in DSpace on 2015-03-26T13:46:57Z (GMT). No. of bitstreams: 1 texto completo.pdf: 3876616 bytes, checksum: c9c4e52759aa0a34b8a0630e1d0ae55e (MD5) Previous issue date: 2011-03-14 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Effective treatment for spinal cord injury remains subject of several studies. Cell therapy is considered an option promising for lesions of the central nervous system, particularly stem cells after experimental animal models showed the transplantation of bone marrow-derived cells results in amelioration of the functional deficit in various neurological diseases. This work evaluated the effect of an intravenous injection of mesenchymal stem cells (MSCs) in different intervals after compressive spinal cord injury compared to treatment with methylprednisolone (MP) and no treatment. MSCs from rat bone marrow were cultivated and expanded in vitro until transplantation. Spinal cord injury was performed with 2-Fr Fogarty catheter after T9-T10 laminectomy. Animals were randomly divided into five experimental groups with 10 animals each and subjected to different treatments: group (CG), which received only PBS; MP group (GM), who received 30 mg/kg SSMP three hours after injury, group 3 hours (GCT), which received administration of MSCs three hours after induction of injury, group 3 days (G3D), received the MSC after three days of injury; and group 7 days (G7D), received MSC seven days after spinal cord injury. Animals were evaluated weekly using the Basso-Beattie-Bresnahan (BBB) open field locomotor test. 35 days after the lesion was performed histological evaluation. All groups treated with MSC showed better results in the motor recovery. The BBB test revealed no difference between GC and GM. In morphometric analysis, the groups treated with MSC showed minor injury area and a higher percentage of healthy tissue than other groups. No differences were observed between groups in the GM and GC analysis histology. It was found that cell therapy with MSCs contributes positively in clinical recovery and preservation of nervous tissue after compressive spinal cord injury. / O tratamento efetivo para pacientes com lesão medular é motivo de diversas pesquisas. Após a obtenção de resultados satisfatórios em vários modelos experimentais, a terapia celular é considerada uma opção promissora para lesões do sistema nervoso central, sobretudo com a utilização de células-tronco. O presente trabalho avaliou o uso de células-tronco mesenquimais (CTM) indiferenciadas em diferentes intervalos de aplicação endovenosa após lesão medular compressiva e realizou estudo comparativo com succinato sódico de metilprednisolona (SSMP) e nenhum tratamento. As CTM foram obtidas da medula óssea de ratos Wistar, cultivadas, caracterizadas e transplantadas na sexta passagem para animais com lesão medular. A lesão medular foi realizada com a introdução do cateter de Fogarty n.º 2 Fr. no espaço epidural T8 e insuflação do cuff com 50&#956;L de salina por cinco minutos, após laminectomia das vértebras T9 e T10. Os animais foram distribuídos aleatoriamente em cinco grupos experimentais com 10 animais em cada e, submetidos a tratamentos distintos: grupo controle (GC), que recebeu aplicação de PBS; grupo metilprednisolona (GM), que recebeu 30mg/Kg de SSMP três horas após a lesão; grupo 3 horas (GCT), que recebeu administração das CTM três horas após a indução da lesão; grupo 3 dias (G3D), que recebeu as CTM após três dias da lesão; grupo 7 dias (G7D), que recebeu as CTM após sete dias da lesão medular. Foi realizada avaliação motora com a escala de Basso-Beattie-Bresnehan (BBB), semanalmente, até o 35º dia após a lesão. Em seguida, foi realizada avaliação histológica da área de lesão e percentual de área preservada nos fragmentos craniais e caudais à área de lesão macroscópica e no fragmento contendo a lesão macroscópica. Os três grupos tratados com as CTM apresentaram melhores índices de recuperação da função motora na escala de BBB, estatisticamente diferentes dos grupos GC e GM. Não foi observada diferença estatística entre os grupos GC e GM quanto à recuperação motora, através dos índices da escala de BBB. Na avaliação histológica, os grupos tratados com as CTM exibiram menor área de lesão e maior percentual de tecido nervoso preservado que os outros grupos. Não foi observada diferenças entre os grupos GM e GC na análise histológica. Constatou-se que a terapia celular com CTM derivadas da medula óssea de ratos Wistar contribui positivamente na melhora clínica e na preservação do tecido nervoso após lesão medular compressiva.