665 resultados para Polyglutamine Tracts
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Pen-and-ink and watercolor.
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Mutations in the SPG4 gene (SPG4-HSP) are the most frequent cause of hereditary spastic paraplegia, but the extent of the neurodegeneration related to the disease is not yet known. Therefore, our objective is to identify regions of the central nervous system damaged in patients with SPG4-HSP using a multi-modal neuroimaging approach. In addition, we aimed to identify possible clinical correlates of such damage. Eleven patients (mean age 46.0 ± 15.0 years, 8 men) with molecular confirmation of hereditary spastic paraplegia, and 23 matched healthy controls (mean age 51.4 ± 14.1years, 17 men) underwent MRI scans in a 3T scanner. We used 3D T1 images to perform volumetric measurements of the brain and spinal cord. We then performed tract-based spatial statistics and tractography analyses of diffusion tensor images to assess microstructural integrity of white matter tracts. Disease severity was quantified with the Spastic Paraplegia Rating Scale. Correlations were then carried out between MRI metrics and clinical data. Volumetric analyses did not identify macroscopic abnormalities in the brain of hereditary spastic paraplegia patients. In contrast, we found extensive fractional anisotropy reduction in the corticospinal tracts, cingulate gyri and splenium of the corpus callosum. Spinal cord morphometry identified atrophy without flattening in the group of patients with hereditary spastic paraplegia. Fractional anisotropy of the corpus callosum and pyramidal tracts did correlate with disease severity. Hereditary spastic paraplegia is characterized by relative sparing of the cortical mantle and remarkable damage to the distal portions of the corticospinal tracts, extending into the spinal cord.
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G-quadruplexes are secondary structures present in DNA and RNA molecules, which are formed by stacking of G-quartets (i.e., interaction of four guanines (G-tracts) bounded by Hoogsteen hydrogen bonding). Human PAX9 intron 1 has a putative G-quadruplex-forming region located near exon 1, which is present in all known sequenced placental mammals. Using circular dichroism (CD) analysis and CD melting, we showed that these sequences are able to form highly stable quadruplex structures. Due to the proximity of the quadruplex structure to exon-intron boundary, we used a validated double-reporter splicing assay and qPCR to analyze its role on splicing efficiency. The human quadruplex was shown to have a key role on splicing efficiency of PAX9 intron 1, as a mutation that abolished quadruplex formation decreased dramatically the splicing efficiency of human PAX9 intron 1. The less stable, rat quadruplex had a less efficient splicing when compared to human sequences. Additionally, the treatment with 360A, a strong ligand that stabilizes quadruplex structures, further increased splicing efficiency of human PAX9 intron 1. Altogether, these results provide evidences that G-quadruplex structures are involved in splicing efficiency of PAX9 intron 1.
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OBJETIVO: Analisar os fatores relacionados à determinação e às desigualdades no acesso e uso dos serviços de saúde por idosos. MÉTODOS: Estudo integrante do Projeto Saúde, Bem-estar e Envelhecimento (SABE), no qual foram entrevistados 2.143 indivíduos com 60 anos ou mais no município de São Paulo, SP, em 2000. A amostra foi obtida em dois estágios, utilizando-se setores censitários com reposição, probabilidade proporcional à população e complementação da amostra de pessoas de 75 anos. Foi mensurado o uso de serviços hospitalares e ambulatoriais nos quatro meses anteriores à entrevista, relacionando-os com fatores de capacidade, necessidade e predisposição (renda total, escolaridade, seguro saúde, morbidade referida, auto-percepção, sexo e idade). O método estatístico utilizado foi regressão logística multivariada. RESULTADOS: Dos entrevistados, 4,7% referiram ter utilizado a internação hospitalar e 64,4% o atendimento ambulatorial. Dos atendimentos ambulatoriais em serviço público, 24,7% ocorreram em hospital e 24,1% em serviço ambulatorial; dentre os que ocorreram em serviços privados, 14,5% foram em hospital e 33,7% em clínicas. Pela análise multivariada, observou-se associação entre a utilização de serviços e sexo, presença de doenças, auto-percepção de saúde, interação da renda e escolaridade e posse de seguro saúde. A análise isolada com escolaridade apresentou efeito inverso. CONCLUSÕES: Foram observadas desigualdades no uso e acesso aos serviços de saúde e inadequação do modelo de atenção, indicando necessidade de políticas públicas que levem em conta as especificidades dessa população, facilitem o acesso e possam reduzir essas desigualdades.
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OBJETIVO: Desenvolver método para planejamento e avaliação de campanhas de vacinação contra a raiva animal. MÉTODOS: O desenvolvimento da metodologia baseou-se em sistemas de informação geográfica para estimar a população e a densidade animal (canina e felina) por setores censitários e subprefeituras do município de São Paulo, em 2002. O número de postos de vacinação foi estimado para atingir uma dada cobertura vacinal. Foram utilizadas uma base de dados censitários para a população humana, e estimativas para razões cão:habitante e gato:habitante. RESULTADOS: Os números estimados foram de 1.490.500 cães e 226.954 gatos em São Paulo, uma densidade populacional de 1.138,14 animais domiciliados por km². Foram vacinados, na campanha de 2002, 926.462 animais, garantindo uma cobertura vacinal de 54%. O número total estimado de postos no município para atingir uma cobertura vacinal de 70%, vacinando em média 700 animais por posto foi de 1.729. Estas estimativas foram apresentadas em mapas de densidade animal, segundo setores censitários e subprefeituras. CONCLUSÕES: A metodologia desenvolvida pode ser aplicada de forma sistemática no planejamento e no acompanhamento das campanhas de vacinação contra a raiva, permitindo que sejam identificadas áreas de cobertura vacinal crítica.
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A clamidiose ou ornitose é uma doença infecciosa, causada pela bactéria Chlamydophila psittaci, que acomete aves e mamíferos. Trata-se de uma das principais zoonoses de origem aviária. A transmissão ocorre principalmente por inalação de secreções contaminadas. Os sinais clínicos mais comuns incluem alterações no sistema gastrointestinal, respiratório e ocular, porém é possível encontrar aves infectadas sem sinais aparentes, dificultando a identificação da doença. O diagnóstico definitivo em aves vivas pode ser difícil, devido às características da infecção pela bactéria. Há duas principais abordagens para o diagnóstico, a primeira envolve a detecção direta da bactéria e a segunda implica a detecção de anticorpos anti-Chlamydophila sp. O tratamento é longo e envolve o uso de tetraciclinas, quinolonas ou macrolídeos, durante 21-45 dias, dependendo da espécie e do fármaco de escolha. Atualmente, o Brasil não dispõe de medidas padronizadas que visam a guiar o clínico na identificação, manejo e tratamento para a doença. Tais medidas tornam-se necessárias, bem como a pesquisa de novos métodos diagnósticos e auxiliares para a doença.
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OBJETIVO: Identificar diferenciais intra-urbanos e fatores de risco na prevalência de baixo peso ao nascer. MÉTODOS: Foram utilizadas as informações das declarações de nascido vivo de mães residentes no município de São Paulo, obtidos do Sistema de Informação de Nascidos Vivos e Fundação Seade, para o período de 2002 e 2003, totalizando 368.980 nascidos vivos. Os endereços foram geo-referenciados em setores censitários e classificados em seis grupos de vulnerabilidade segundo o Índice Paulista de Vulnerabilidade Social. Para identificação dos possíveis fatores de risco empregou-se análise de regressão logística. RESULTADOS: Observou-se tendência de crescimento da prevalência de baixo peso ao nascer com aumento da vulnerabilidade (de 6,8% a 8,1%). Houve diferenças significativas entre os grupos quanto às características maternas, assistência pré-natal e da proporção de nascimentos de não pré-termo de baixo peso. No grupo de baixo peso não pré-termo, proxy da presença de retardo do crescimento intra-uterino, residir em áreas vulneráveis (1,29;1,17-1,43) e características socioeconômicas maternas desaforáveis, como mães adolescentes (1,13;1,04-1,22), baixa escolaridade (1,26;1,17-1,35) e elevada paridade (1,10;1,01-1,20) foram fatores de risco, assim como mães idosas (1,38;1,30-1,47), e sem companheiro (1,15;1,11-1,20). A ausência de pré-natal apresentou o maior risco de baixo peso para nascimentos de pré-termo (3,39;2,86-4,02) e não pré-termo (2,12;1,87-2,41). Houve redução de risco de baixo peso com o aumento de consultas de pré-natal para nascimentos de pré-termo e não pré-termo. CONCLUSÕES: Há diferenças de prevalência de baixo peso ao nascer segundo grupos de vulnerabilidade. A assistência pré-natal mostrou-se desigual segundo grupos de vulnerabilidade e seu elevado risco para o baixo peso ao nascer indica a importância de ampliar o acesso e qualidade dos serviços de saúde
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Skp1, Cul1, Rbx1, and the FBXO25 protein form a functional ubiquitin ligase complex. Here, we investigate the cellular distribution of FBXO25 and its colocalization with some nuclear proteins by using immunochemical and biochemical approaches. FBXO25 was monitored with affinity-purified antibodies raised against the recombinant fragment spanning residues 2-62 of the FBXO25 sequence. FBXO25 protein was expressed in all mouse tissues tested except striated muscle, as indicated by immunoblot analysis. Confocal analysis revealed that the endogenous FBXO25 was partially concentrated in a novel dot-like nuclear domain that is distinct from clastosomes and other well-characterized structures. These nuclear compartments contain a high concentration of ubiquitin conjugates and at least two other components of the ubiquitin-proteasome system: 20S proteasome and Skp1. We propose to name these compartments FBXO25-associated nuclear domains. Interestingly, inhibition of transcription by actinomycin D or heat-shock treatment drastically affected the nuclear organization of FBXO25-containing structures, indicating that they are dynamic compartments influenced by the transcriptional activity of the cell. Also, we present evidences that an FBXO25-dependent ubiquitin ligase activity prevents aggregation of recombinant polyglutamine-containing huntingtin protein in the nucleus of human embryonic kidney 293 cells, suggesting that this protein can be a target for the nuclear FBXO25 mediated ubiquitination.
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Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[06/56855-0]
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Secondary neurodegeneration takes place in the surrounding tissue of spinal cord trauma and modifies substantially the prognosis, considering the small diameter of its transversal axis. We analyzed neuronal and glial responses in rat spinal cord after different degree of contusion promoted by the NYU Impactor. Rats were submitted to vertebrae laminectomy and received moderate or severe contusions. Control animals were sham operated. After 7 and 30 days post surgery, stereological analysis of Nissl staining cellular profiles showed a time progression of the lesion volume after moderate injury, but not after severe injury. The number of neurons was not altered cranial to injury. However, same degree of diminution was seen in the caudal cord 30 days after both severe and moderate injuries. Microdensitometric image analysis demonstrated a microglial reaction in the white matter 30 days after a moderate contusion and showed a widespread astroglial reaction in the white and gray matters 7 days after both severities. Astroglial activation lasted close to lesion and in areas related to Wallerian degeneration. Data showed a more protracted secondary degeneration in rat spinal cord after mild contusion, which offered an opportunity for neuroprotective approaches. Temporal and regional glial responses corroborated to diverse glial cell function in lesioned spinal cord. (C) 2007 Elsevier Ltd. All rights reserved.
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Tropical countries face special specific problems in implementing sustainable forest management (SFM). In many countries, questions are raised on whether tropical forests should be publicly, commonly or privately owned and managed in order to enhance sustainability. Other debates also focus on whether small-scale enterprises are better positioned than large-scale industrial concessions to reduce poverty and attain sustainable management. In countries where large tracts of forest are state-owned, concessions are viewed as a means of delivering services of public and collective interest through an association of private investment and public regulation. However, the success of an industrial concession model in countries with large forest resource endowment to achieve multiple goals such as sustainable forest management and local/regional development depends on two critical assumptions. First, forest functions and services should be managed and maintained as public goods. In many cases, additional uses - and corresponding rights - can take place alongside logging activities. Industrial concessions can be more efficient than other tenure models (such as community-based forest management and small-scale enterprises) in achieving SFM, add value to raw material and comply with growing environmental norms. This is especially the case in market-remote areas with low population density and poor infrastructure. Secondly, to achieve these different outcomes, any concession system needs to be monitored and regulated, especially in contexts dominated by asymmetrical information between regulating authorities and concessionaires. New institutional responses have recently been put forward in several countries, providing valuable materials to design a renewed policy mix which associates public and private incentives. This paper provides a survey of the experience of forest concessions in several Central African and South American countries. The concession system is examined in order to clarify the issues involved, the problems encountered, and what can be learned from the shared experience of these countries in the last decade. This paper argues that despite a sometimes patchy record, concessions can help promote SFM so long as they are packaged with a certain number of specific measures. (C) 2008 Elsevier B.V. All rights reserved.
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We investigated the inhibitory potential of aqueous extracts of bark and leaves of Esenbeckia leiocarpa Engl. on lettuce germination and early seedling growth. We compared the effects of four concentrations (100, 75, 50 and 25%) of each extract to water and polyethylene glycol (PEG 6000) solution controls for four replicates of 50 seeds tor germination and four replicates of ten seedlings for seedling growth. The inhibitory effects of E. leiocarpa extracts on the percentage of germination and on the germination speed seemed to be inure than simply an osmotic effect, except for the percentage of seeds germinated in bark extracts. When compared to water control. both bark and leaf extracts delayed germination, and leaf extracts also affected the percentage of germinated seeds. Leaf ex tracts of all concentrations strongly inhibited the development of seedlings and caused them some degree of abnormality; bark extracts also caused abnormalities and reduced seedling growth. Root development was more sensitive to the extracts than hypocotyl growth. The negative effects of leaf extracts on germination and seedling growth were more pronounced than those of bark extracts, and the overall effects of both extracts were positively correlated with extract concentrations.
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In the developing vertebrate brain, growing axons establish a scaffold of axon tracts connected across the midline via commissures. We have previously identified a population of telencephalic neurons that express NOC-2, a novel glycoform of the neural cell adhesion molecule N-CAM that is involved in axon guidance in the forebrain. These axons arise from the presumptive telencephalic nucleus, course caudally along the principal longitudinal tract of the forebrain, cross the ventral midline in the midbrain, and then project to the contralateral side of the brain. In the present study we have investigated mechanisms controlling the growth of these axons across the ventral midline of the midbrain. The axon guidance receptor DCC is expressed by the NOC-2 population of axons both within the longitudinal tract and within the ventral midbrain commissure. Disruption of DCC-dependent interactions, both in vitro and in vivo, inhibited the NOC-2 axons from crossing the ventral midbrain. Instead, these axons grew along aberrant trajectories away from the midline, suggesting that DCC-dependent interactions are important for overcoming inhibitory mechanisms within the midbrain of the embryonic vertebrate brain. Thus, coordinated responsiveness of forebrain axons to both chemostimulatory and chemorepulsive cues appears to determine whether they cross the ventral midline in the midbrain, (C) 2000 Academic Press.
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A novel MRI method-diffusion tensor imaging-was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimer's disease, in which global cognitive decline is a more prominent feature than motor disturbance.
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Diverse self-incompatibility (SI) mechanisms permit flowering plants to inhibit fertilization by pollen that express specificities in common with the pistil. Characteristic of at least two model systems is greatly reduced recombination across large genomic tracts surrounding the S-locus, which regulates SI. In three angiosperm families, including the Solanaceae, the gene that controls the expression of gametophytic SI in the pistil encodes a ribonuclease (S-RNase). The gene that controls pollen SI expression is currently unknown, although several candidates have recently been proposed. Although each candidate shows a high level of polymorphism and complete allelic disequilibrium with the S-RNase gene, such properties may merely reflect tight linkage to the S-locus, irrespective of any functional role in SI. We analyzed the magnitude and nature of nucleotide variation, with the objective of distinguishing likely candidates for regulators of SI from other genes embedded in the S-locus region. We studied the S-RNase gene of the Solanaceae and 48A, a candidate for the pollen gene in this system, and we also conducted a parallel analysis of the regulators of sporophytic SI in Brassica, a system in which both the pistil and pollen genes are known. Although the pattern of variation shown by the pollen gene of the Brassica system is consistent with its role as a determinant of pollen specificity, that of 48A departs from expectation. Our analysis further suggests that recombination between 48A and S-RNase may have occurred during the interval spanned by the gene genealogy, another indication that 48A may not regulate SI expression in pollen.