85 research outputs found

    A REGRESSIVIDADE DEMOCRÁTICA DA BNCC

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    Este artigo consiste em análise documental que evidencia o desrespeito à Constituição Federal e à LDBEN/96 efetivado na BNCC (Base Nacional Comum Curricular). Afirma-se que a BNCC, como documento de caráter normativo, impõe uma única concepção pedagógica e curricular: a Pedagogia e o Currículo por Competências. Ao fazê-lo, desrespeita os princípios constitucionais da pluralidade de concepções pedagógicas, da liberdade de ensinar e aprender e o da autonomia das escolas na construção de suas propostas pedagógicas

    Assessment of stainless steel 348 fuel rod performance against literature available data using TRANSURANUS code

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    Submitted by Marco Antonio Oliveira da Silva ([email protected]) on 2016-12-19T18:16:45Z No. of bitstreams: 1 22767.pdf: 301745 bytes, checksum: 6988361c17e5bad3bd430a177b061f79 (MD5) Made available in DSpace on 2016-12-19T18:16:45Z (GMT). No. of bitstreams: 1 22767.pdf: 301745 bytes, checksum: 6988361c17e5bad3bd430a177b061f79 (MD5) Early pressurized water reactors were originally designed to operate using stainless steel as cladding material, but during their lifetime this material was replaced by zirconium-based alloys. However, after the Fukushima Daiichi accident, the problems related to the zirconium-based alloys due to the hydrogen production and explosion under severe accident brought the importance to assess different materials. In this sense, initiatives as ATF (Accident Tolerant Fuel) program are considering different material as fuel cladding and, one candidate is iron-based alloy. In order to assess the fuel performance of fuel rods manufactured using iron-based alloy as cladding material, it was necessary to select a specific stainless steel (type 348) and modify properly conventional fuel performance codes developed in the last decades. Then, 348 stainless steel mechanical and physics properties were introduced in the TRANSURANUS code. The aim of this paper is to present the obtained results concerning the verification of the modified TRANSURANUS code version against data collected from the open literature, related to reactors which operated using stainless steel as cladding. Considering that some data were not available, some assumptions had to be made. Important differences related to the conventional fuel rods were taken into account. Obtained results regarding the cladding behavior are in agreement with available information. This constitutes an evidence of the modified TRANSURANUS code capabilities to perform fuel rod investigation of fuel rods manufactured using 348 stainless steel as cladding material

    Cell adhesion molecule L1 contributes to neuronal excitability regulating the function of voltage-gated Na+ channels

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    L1 (also known as L1CAM) is a trans-membrane glycoprotein mediating neuron-neuron adhesion through homophilic and heterophilic interactions. Although experimental evidence has implicated L1 in axonal outgrowth, fasciculation and pathfinding, its contribution to voltage-gated Na+ channel function and membrane excitability has remained unknown. Here, we show that firing rate, single cell spiking frequency and Na+ current density are all reduced in hippocampal excitatory neurons from L1-deficient mice both in culture and in slices owing to an overall reduced membrane expression of Na+ channels. Remarkably, normal firing activity was restored when L1 was reintroduced into L1-deficient excitatory neurons, indicating that abnormal firing patterns are not related to developmental abnormalities, but are a direct consequence of L1 deletion. Moreover, L1 deficiency leads to impairment of action potential initiation, most likely due to the loss of the interaction of L1 with ankyrin G that produces the delocalization of Na+ channels at the axonal initial segment. We conclude that L1 contributes to functional expression and localization of Na+ channels to the neuronal plasma membrane, ensuring correct initiation of action potential and normal firing activity

    Recruitment of Endophilin to Clathrin-Coated Pit Necks Is Required for Efficient Vesicle Uncoating after Fission

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    SummaryEndophilin is a membrane-binding protein with curvature-generating and -sensing properties that participates in clathrin-dependent endocytosis of synaptic vesicle membranes. Endophilin also binds the GTPase dynamin and the phosphoinositide phosphatase synaptojanin and is thought to coordinate constriction of coated pits with membrane fission (via dynamin) and subsequent uncoating (via synaptojanin). We show that although synaptojanin is recruited by endophilin at bud necks before fission, the knockout of all three mouse endophilins results in the accumulation of clathrin-coated vesicles, but not of clathrin-coated pits, at synapses. The absence of endophilin impairs but does not abolish synaptic transmission and results in perinatal lethality, whereas partial endophilin absence causes severe neurological defects, including epilepsy and neurodegeneration. Our data support a model in which endophilin recruitment to coated pit necks, because of its curvature-sensing properties, primes vesicle buds for subsequent uncoating after membrane fission, without being critically required for the fission reaction itself

    Autoantibodies to synapsin I sequestrate synapsin I and alter synaptic function

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    Synapsin I is a phosphoprotein that coats the cytoplasmic side of synaptic vesicles and regulates their trafficking within nerve terminals. Autoantibodies against Syn I have been described in sera and cerebrospinal fluids of patients with numerous neurological diseases, including limbic encephalitis and clinically isolated syndrome; however, the effects and fate of autoantibodies in neurons are still unexplored. We found that in vitro exposure of primary hippocampal neurons to patient\u2019s autoantibodies to SynI decreased the density of excitatory and inhibitory synapses and impaired both glutamatergic and GABAergic synaptic transmission. These effects were reproduced with a purified SynI antibody and completely absent in SynI knockout neurons. Autoantibodies to SynI are internalized by Fc\u3b3II/III-mediated endocytosis, interact with endogenous SynI, and promote its sequestration and intracellular aggregation. Neurons exposed to human autoantibodies to SynI display a reduced density of SVs, mimicking the SynI loss-of-function phenotype. Our data indicate that autoantibodies to intracellular antigens such as SynI can reach and inactivate their targets and suggest that an antibody-mediated synaptic dysfunction may contribute to the evolution and progression of autoimmune-mediated neurological diseases positive for SynI autoantibodies

    Comparative clinical evaluation of progressive addition lenses in presbyopia

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    OBJETIVO: Avaliar o desempenho clínico de lentes progressivas (LP) em présbitas amétropes, comparando LP Gradal Top® às LP que usavam. MÉTODOS: Realizou-se um estudo clínico com 40 présbitas satisfeitos com seus óculos com adição <2,00D, atualizados e aviados com LP de várias marcas. Todos foram submetidos a exame oftalmológico completo e receberam os novos óculos com lentes progressivas Gradal Top® fornecidos sem custo por Carl Zeiss Vision do Brasil. As avaliações foram feitas em entrevista durante a qual se anotavam os resultados. Para a avaliação do desempenho clínico das LP foram utilizados três questionários. O primeiro foi respondido quando do fornecimento dos novos óculos e dizia respeito à avaliação das LP em uso. Os outros dois foram respondidos após 2 a 3 semanas de uso dos LP Gradal Top®. O desempenho visual foi avaliado com notas de 1 a 10, sendo consideradas a qualidade da visão de perto, intermediária e dinâmica (passagem da visão de perto para a intermediária), adaptação e satisfação geral com as LP e preferência entre as LP anteriores e as LP Gradal Top®. RESULTADOS: Em todos os itens constantes dos questionários o desempenho visual de Gradal Top® foi superior àquele das LP anteriores. Em comparação aos óculos que usavam, 33 présbitas (82,5%) preferiram Gradal Top® e 5 (12,5%) preferiram as LP anteriores. Para dois présbitas (5%) não houve diferença. CONCLUSÃO: Na maioria dos présbitas amétropes estudados as LP Gradal Top® demonstraram desempenho clínico superior às LP anteriormente usadas.PURPOSE: To study the clinical performance of progressive addition lens (PAL) Gradal Top®, Carl Zeiss Vision compared with other PAL lenses previously worn by presbyopic ametropes. METHODS: Forty presbyopes satisfied with their PAL spectacles (addition <2.00D) were included in the study. Following a complete ophthalmologic examination all presbyopes received new prescription glasses fitted with Gradal Top® PAL supplied by Carl Zeiss Vision Brasil at no cost. Evaluation occurred during an interview and the results were recorded in three different forms. The first form concerned the PAL formerly worn and was completed at delivery of the new glasses. The two remaining forms were completed two or three weeks after wearing Gradal Top®. The visual performance was graded from 1 to 10, and concerned near, intermediate and dynamic (shift from near to intermediate) visual acuity, patient adjustment to PAL and patient satisfaction. RESULTS: According to all variables on the record form, visual performance with Gradal Top® was better than with the previously worn PAL. Thirty-three patients (82.5%) preferred Gradal Top®, five patients (12.5%) preferred their former PAL and two patients (5%) showed no preference. CONCLUSION: For most of the studied patients Gradal Top® showed better clinical performance than the formerly worn PAL

    Structural determinants of the specificity for synaptic vesicle-associated membrane protein/synaptobrevin of tetanus and botulinum type B and G neurotoxins

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    Tetanus and botulinum neurotoxins type B and G are zinc-endopeptidases of remarkable specificity. They recognize and cleave a synaptic vesicle- associated membrane protein (VAMP)/synaptobrevin, an essential protein component of the vesicle docking and fusion apparatus. VAMP contains two copies of a nine-residue motif, also present in SNAP-25 (synaptosomal- associated protein of 25 kDa) and syntaxin, the two other substrates of clostridial neurotoxins. This motif was suggested to be a determinant of the target specificity of neurotoxins. Antibodies raised against this motif cross-react among VAMP, SNAP-25, and syntaxin and inhibit the proteolytic activity of the neurotoxins. Moreover, the various neurotoxins cross-inhibit each other's proteolytic action. The role of the three negatively charged residues of the motif in neurotoxin recognition was probed by site-directed mutagenesis. Substitution of acidic residues in both copies of the VAMP motif indicate that the first one is involved in tetanus neurotoxin recognition, whereas the second one is implicated in binding botulinum B and G neurotoxins. These results suggest that the two copies of the motif have a tandem association in the VAMP molecule

    Altered synaptobrevin-II trafficking in neurons expressing a synaptophysin mutation associated with a severe neurodevelopmental disorder

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    textabstractFollowing exocytosis, synaptic vesicles (SVs) have to be reformed with the correct complement of proteins in the correct stoichiometry to ensure continued neurotransmission. Synaptophysin is a highly abundant, integral SV protein necessary for the efficient retrieval of the SV SNARE protein, synaptobrevin II (sybII). However the molecular mechanism underpinning synaptophysin-dependent sybII retrieval is still unclear. We recently identified a male patient with severe intellectual disability, hypotonia, epilepsy and callosal agenesis who has a point mutation in the juxtamembrane region of the fourth transmembrane domain of synaptophysin (T198I). This mutation had no effect on the activity-dependent retrieval of synaptophysin that was tagged with the genetically-encoded pH-sensitive reporter (pHluorin) in synaptophysin knockout hippocampal cultures. This suggested the mutant has no global effect on SV endocytosis, which was confirmed when retrieval of a different SV cargo (the glutamate transporter vGLUT1) was examined. However neurons expressing this T198I mutant did display impaired activity-dependent sybII retrieval, similar to that observed in synaptophysin knockout neurons. Interestingly this impairment did not result in an increased stranding of sybII at the plasma membrane. Screening of known human synaptophysin mutations revealed a similar presynaptic phenotype between T198I and a mutation found in X-linked intellectual disability. Thus this novel human synaptophysin mutation has revealed that aberrant retrieval and increased plasma membrane localisation of SV cargo can be decoupled in human disease
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