The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals.

Collective evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is non-cell-autonomous and requires the interaction with the neighboring astrocytes. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1(G93A) mouse model of ALS. Mechanistic studies in vitro identified a role for the excitatory amino acid glutamate in the gliodegenerative process via the activation of its inositol 1,4,5-triphosphate (IP(3))-generating metabotropic receptor 5 (mGluR5). Since non-physiological formation of IP(3) can prompt IP(3) receptor (IP(3)R)-mediated Ca(2+) release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca(2+) signaling that occurs downstream of mGluR5 in hSOD1(G93A)-expressing astrocytes. Contrary to wild-type cells, stimulation of mGluR5 causes aberrant and persistent elevations of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in the absence of spontaneous oscillations. The interaction of IP(3)Rs with the anti-apoptotic protein Bcl-X(L) was previously described to prevent cell death by modulating intracellular Ca(2+) signals. In mutant SOD1-expressing astrocytes, we found that the sole BH4 domain of Bcl-X(L), fused to the protein transduction domain of the HIV-1 TAT protein (TAT-BH4), is sufficient to restore sustained Ca(2+) oscillations and cell death resistance. Furthermore, chronic treatment of hSOD1(G93A) mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. Our results point at TAT-BH4 as a novel glioprotective agent with a therapeutic potential for ALS.

Pesquisa disciplinar do corpus documental das teses de doutorado do PPGCI-IBICT/UFRJ: aplicando princípios e categorias para estudo interdisciplinar da ciência da informação no Brasil

A partir do histórico da ciência da informação no Brasil, realizou-se estudo visando a investigar, mediante princípios e categorias, a relação das disciplinas com a ciência da informação. O modelo aplicado dividiu o corpus de 58 teses em três categorias: disciplinas como conjuntos distintos, já que os conceitos e métodos dessa categoria não são suficientes para formalizar um quadro interdisciplinar. A segunda pela interação dos conceitos abordados, com encadeamento das questões colocadas pelas disciplinas na busca de solução para o problema proposto. A terceira remete à integração entre a disciplina e a ciência da informação, apresentando uma linguagem comum. O resultado do estudo visa a contribuir para a criação de um método de pesquisa interdisciplinar para a pós-graduação brasileira.

Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element.

The malic enzyme (ME) gene is a target for both thyroid hormone receptors and peroxisome proliferator-activated receptors (PPAR). Within the ME promoter, two direct repeat (DR)-1-like elements, MEp and MEd, have been identified as putative PPAR response elements (PPRE). We demonstrate that only MEp and not MEd is able to bind PPAR/retinoid X receptor (RXR) heterodimers and mediate peroxisome proliferator signaling. Taking advantage of the close sequence resemblance of MEp and MEd, we have identified crucial determinants of a PPRE. Using reciprocal mutation analyses of these two elements, we show the preference for adenine as the spacing nucleotide between the two half-sites of the PPRE and demonstrate the importance of the two first bases flanking the core DR1 in 5'. This latter feature of the PPRE lead us to consider the polarity of the PPAR/RXR heterodimer bound to its cognate element. We demonstrate that, in contrast to the polarity of RXR/TR and RXR/RAR bound to DR4 and DR5 elements respectively, PPAR binds to the 5' extended half-site of the response element, while RXR occupies the 3' half-site. Consistent with this polarity is our finding that formation and binding of the PPAR/RXR heterodimer requires an intact hinge T region in RXR while its integrity is not required for binding of the RXR/TR heterodimer to a DR4.

Catalogue d'une collection de bons tableaux... par suite du décès de M. X... [Rossard, De Courbonne] / [expert] Febvre

[Vente. Art. 1857-12-24. Paris]

Evolutionary history of the greater white-toothed shrew (Crocidura russula) inferred from analysis of mtDNA, Y, and X chromosome markers.

We investigate the evolutionary history of the greater white-toothed shrew across its distribution in northern Africa and mainland Europe using sex-specific (mtDNA and Y chromosome) and biparental (X chromosome) markers. All three loci confirm a large divergence between eastern (Tunisia and Sardinia) and western (Morocco and mainland Europe) lineages, and application of a molecular clock to mtDNA divergence estimates indicates a more ancient separation (2.25 M yr ago) than described by some previous studies, supporting claims for taxonomic revision. Moroccan ancestry for the mainland European population is inconclusive from phylogenetic trees, but is supported by greater nucleotide diversity and a more ancient population expansion in Morocco than in Europe. Signatures of rapid population expansion in mtDNA, combined with low X and Y chromosome diversity, suggest a single colonization of mainland Europe by a small number of Moroccan shrews >38 K yr ago. This study illustrates that multilocus genetic analyses can facilitate the interpretation of species' evolutionary history but that phylogeographic inference using X and Y chromosomes is restricted by low levels of observed polymorphism.

Catalogue d'une collection de tableaux anciens... provenant du cabinet de M. X***,... / [expert] Febvre

[Vente. Art. 1859-05-20. Paris]

Importância das interações cultivares x locais e cultivares x anos na avaliação de milho na safrinha

Com o objetivo de verificar a importância da interação cultivares x locais e cultivares x anos e de identificar entre os híbridos já disponíveis os que sejam mais adaptados e estáveis para o cultivo em safrinha, foram estimados os parâmetros de adaptabilidade e estabilidade a partir de dados obtidos em experimentos de avaliação de cultivares de milho na safrinha, nos anos de 1993, 1994 e 1995. Esses experimentos foram conduzidos nos Estados de São Paulo, Goiás e Paraná. O delineamento utilizado foi em blocos casualizados com três repetições. Constatou-se que a magnitude da variância da interação cultivares com anos dentro de locais foi mais expressiva do que entre locais, o que indica a necessidade de que as avaliações de cultivares na safrinha sejam realizadas num maior número de anos. As cultivares diferiram quanto à adaptabilidade e estabilidade de produção de grãos. Os materiais que se destacaram como mais adaptados e estáveis foram o híbrido simples Zeneca 8452, o híbrido triplo C 805 e o híbrido duplo Agromen 2012. Já os híbridos duplos BR 201, Planagri 411, AG 303 e C 125 foram os que mostraram menor adaptação e maior instabilidade.

Evaluation of Carbonate Aggregate Using X-Ray Analysis, HR-266, 1989

Iowa has more than 13,000 miles of portland cement concrete (PCC) pavement. Some pavements have performed well for over 50 years, while others have been removed or overlaid due to the premature deterioration of joints and cracks. Some of the premature deterioration is classical D-cracking, which is attributed to a critically saturated aggregate pore system (freeze-thaw damage). However, some of the premature deterioration is related to adverse chemical reactivity involving carbonate coarse aggregate. The objective of this paper is to demonstrate the value of a chemical analysis of carbonate aggregate using X-ray equipment to identify good or poor quality. At least 1.5% dolomite is necessary in a carbonate aggregate to produce a discernible dolomite peak. The shift of the maximum-intensity X-ray diffraction dolomite d-spacing can be used to predict poor performance of a carbonate aggregate in PCC. A limestone aggregate with a low percentage of strontium (less than 0.013) and phosphorus (less than 0.010) would be expected to give good performance in PCC pavement. Poor performance in PCC pavement is expected from limestone aggregates with higher percentages (above 0.05) of strontium.

Kantisme i sentit comú en Francesc X. Llorens i Barba

L'objectiu de l'article és analitzar quin sentit té el kantisme a la filosofia de Llorens i Barba. S'ha afirmat sovint que potser Llorens es va distanciar de Kant al final de la seva vida. Aquesta qüestió ens pot ocultar quelcom més important: el veritable significat dels elements d'ètica kantiana dins de la filosofia de Llorens. Mostrarem que la influència de Kant és clara, però que cal tenir present que deriva igualment de la principal font de Llorens, el filòsof escocès William Hamilton. Per assolir aquesta conclusió analitzarem la presència de la noció de sentit comú en Kant i considerarem de quina manera l'ètica complementa la metafísica en Kant, Hamilton i Llorens.

Peroxisome proliferator-activated receptor mediates cross-talk with thyroid hormone receptor by competition for retinoid X receptor. Possible role of a leucine zipper-like heptad repeat.

The peroxisome proliferator-activated receptors (PPAR) and thyroid hormone receptors (TR) are members of the nuclear receptor superfamily, which regulate lipid metabolism and tissue differentiation. In order to bind to DNA and activate transcription, PPAR requires the formation of heterodimers with the retinoid X receptor (RXR). In addition to activating transcription through its own response elements, PPAR is able to selectively down-regulate the transcriptional activity of TR, but not vitamin D receptor. The molecular basis of this functional interaction has not been fully elucidated. By means of site-directed mutagenesis of hPPAR alpha we mapped its inhibitory action on TR to a leucine zipper-like motif in the ligand binding domain of PPAR, which is highly conserved among all subtypes of this receptor and mediates heterodimerization with RXR. Replacement of a single leucine by arginine at position 433 of hPPAR alpha (L433R) abolished heterodimerization of PPAR with RXR and consequently its trans-activating capacity. However, a similar mutation of a leucine residue to arginine at position 422 showed no alteration of heterodimerization, DNA binding, or transcriptional activation. The dimerization deficient mutant L433R was no longer able to inhibit TR action, demonstrating that the selective inhibitory effect of PPAR results from the competition for RXR as well as possibly for other TR-auxiliary proteins. In contrast, abolition of DNA binding by a mutation in the P-box of PPAR (C122S) did not eliminate the inhibition of TR trans-activation, indicating that competition for DNA binding is not involved. Additionally, no evidence for the formation of PPAR:TR heterodimers was found in co-immunoprecipitation experiments. In summary, we have demonstrated that PPAR selectively inhibits the transcriptional activity of TRs by competition for RXR and possibly non-RXR TR-auxiliary proteins. In contrast, this functional interaction is independent of the formation of PPAR:TR heterodimers or competition for DNA binding.

Caracterização química da carne de cabrito da raça Moxotó e de cruzas Pardo Alpina x Moxotó

O objetivo da pesquisa foi avaliar a composição química da carne de cabrito-mamão (idade média de 72 dias), da raça Moxotó (MOX), grupos genéticos ¾ Pardo Alpina x ¼ Moxotó (3/4 PAMOX) e ½ Pardo Alpina x ½ Moxotó (1/2 PAMOX). A análise apresentou valores médios entre 77,80% a 80,25% de umidade; 15,90% a 19,08% de proteína; 1,12% a 1,21% de gordura, e 1,29% a 2,03% de cinzas. Quanto à composição mineral, os valores médios variaram de 5,62 mg/100 g a 8,21 mg/100 g de cálcio; 156,97 mg/100 g a 196,25 mg/100 g de fósforo; 0,26 mg/100 g a 0,48 mg/100 g de ferro; 16,25 mg/100 g a 23,72 mg/100 g de magnésio; 59,20 mg/100 g a 78,79 mg/100 g de sódio, e de 259,69 mg/100 g a 292,24 mg/100 g de potássio. Foram encontradas diferenças significativas a 5% de probabilidade entre os grupos genéticos no que diz respeito à composição de umidade, proteína e cinzas e mineral quanto a elementos estudados. Não houve diferenças entre os valores de gordura dos grupos genéticos.

Crystallization and preliminary X-ray diffraction studies of Drosophila melanogaster Gαo-subunit of heterotrimeric G protein in complex with the RGS domain of CG5036.

Regulator of G-protein signalling (RGS) proteins negatively regulate heterotrimeric G-protein signalling through their conserved RGS domains. RGS domains act as GTPase-activating proteins, accelerating the GTP hydrolysis rate of the activated form of Gα-subunits. Although omnipresent in eukaryotes, RGS proteins have not been adequately analysed in non-mammalian organisms. The Drosophila melanogaster Gαo-subunit and the RGS domain of its interacting partner CG5036 have been overproduced and purified; the crystallization of the complex of the two proteins using PEG 4000 as a crystallizing agent and preliminary X-ray crystallographic analysis are reported. Diffraction data were collected to 2.0 Ã… resolution using a synchrotron-radiation source.

X-Ray Diffraction Studies of Soils and Soil Stabilizers, HR-106, 1965

The two goals of this project stated in the Proposal were: (1) study lime diffusion in clayey soils, and (2) find the role of MgO in soil-dolomitic lime stabilization. Because of the practice significance of these goals we temporarily overstaffed this project, giving somewhat a "crash" program. As a result, proposed work was finished up early (as were the funds), and more important, some of the findings were early enough and of sufficient merit to put into field trials in the Fall of 1964. The work now being completed and the funds all being expended, this Final Report is therefore submitted before the anticipated project termination date.

Clonal variation in nutrient content in woody biomass of hybrid aspen (Populus tremula L. x P. tremuloides Michx.)

Abstract

Effect of CA-Montmorillonite Expansion on X-Ray Diffraction Intensities, Progress Report, HR-111, 1966

The most abundant clay mineral group in Iowa soils is montmorillonite, most commonly calcium-saturated (Hanway et al, 1960). The calcium montmorillonite-water system was therefore selected for detailed X-ray study. Montmorillonite is unusual among minerals in that it has an expanding lattice in the c direction. That is, upon wetting with water, the individual silicate layers separate to allow entry of water, and the mineral expands. Characteristics of this expansion are readily studied by means of X-ray diffraction: the X-ray diffraction angle gives the average layer-to-layer "d001" spacing for any given moisture condition; the sharpness of the diffraction peak is a measure of uniformity of the d001 spacing; and the intensity of the peak relates to uniformity of the d001 spacing and in addition to the electron density distribution within the repeating elements. The latter is embodied in the "structure factor".