Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos.

An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to investigate the influence of glial cells on the neurotoxicity of two organophosphorus pesticides (OPs), chlorpyrifos and parathion. Mixed-cell aggregate cultures were treated continuously for 10 days between DIV 5 and 15. Parathion induced astrogliosis at concentration at which MAP-2 immunostaining, found here to be more sensitive than neuron-specific enzyme activities, was not affected. In contrast, chlorpyrifos induced a comparatively weak gliotic reaction, and only at concentrations at which neurons were already affected. After similar treatments, increased neurotoxicity of parathion and chlorpyrifos was found in aggregate cultures deprived of glial cells. These results suggest that glial cells provide neuroprotection against OPs toxicity. To address the question of the difference in toxicity between parathion and chlorpyrifos, the toxic effects of their leaving groups, p-nitrophenol and trichloropyridinol, were studied in mixed-cell aggregates. General cytotoxicity was more pronounced for trichloropyridinol and both compounds had similar toxic effects on neuron-specific enzyme activities. In contrast, trichloropyridinol induced a much stronger decrease in glutamine synthetase activity, the enzymatic marker of astrocytes. Trichloropyridinol may exert a toxic effect on astrocytes, compromising their neuroprotective function, thus exacerbating the neurotoxicity of chlorpyrifos. This is in line with the suggestion that glial cells may contribute to OPs neurotoxicity, and with the view that OPs may exert their neurotoxic effects through different mechanisms.

Financial development, financial fragility and growth

This paper studies the apparent contradiction between two strands of the literature on the effects of financial intermediation on economic activity. On the one hand, the empirical growth literature finds a positive effect of financial depth as measured by, for instance, private domestic credit and liquid liabilities (e.g., Levine, Loayza, and Beck 2000). On the other hand, the banking and currency crisis literature finds that monetary aggregates, such as domestic credit, are among the best predictors of crises and their related economic downturns (e.g., Kaminski and Reinhart 1999). The paper accounts for these contrasting effects based on the distinction between the short- and long-run impacts of financial intermediation. Working with a panel of cross-country and time-series observations, the paper estimates an encompassing model of short- and long-run effects using the Pooled Mean Group estimator developed by Pesaran, Shin, and Smith (1999). The conclusion from this analysis is that a positive long-run relationship between financial intermediation and output growth co-exists with a, mostly, negative short-run relationship. The paper further develops an explanation for these contrasting effects by relating them to recent theoretical models, by linking the estimated short-run effects to measures of financial fragility(namely, banking crises and financial volatility), and by jointly analyzing the effects of financial depth and fragility in classic panel growth regressions.

Extracção de areia na Praia de Calhetona (Ilha de Santiago, Cabo Verde) : causas, processos e consequências

A extracção de areia nas praias do mar, nas bacias hidrográficas e nas encostas montanhosas, tem sido prática de muitas famílias cabo-verdianas. A Praia de Calhetona foi uma das que nos últimos anos sofreu degradação significativa, em função da apanha clandestina de areia, sem qualquer plano de extracção, destinada a construção civil. A extracção de areia, para vender ou para a autoconstrução, é efectuada em família por indivíduos, maioritariamente do sexo feminino, de baixa renda ou sem profissão remunerada. O processo de extracção de areia na Praia de Calhetona teve o seu ponto alto nos anos 80, diminuindo consideravelmente com a escassez de areia e implementação do Decreto – Lei nº 69/97, de 3 de Novembro, que visava disciplinar a exploração de inertes nas praias. Em face da pesquisa feita, baseada no estudo de caso, ficou expresso que os inquiridos implicados na actividade de extracção clandestina de areia correm riscos elevados para obterem lucros reduzidos. Quem efectivamente beneficia são os camionistas que compram esse inerte e o vendem pelo dobro do preço. Qualquer actividade de exploração de recursos naturais causa impactes sobre o espaço de actuação. No caso da Praia de Calhetona, observa-se o recuo da linha de costa, a quase ausência de areia e a desertificação de propriedades nas suas proximidades, para além dos impactes negativos sobre o turismo, a função balnear e a desova de tartaruga. Apesar de tudo, constata-se uma consciência generalizada dos impactes ambientais causados pelos inquiridos, os quais, no entanto, alegam que a extracção de areia é uma das alternativas para garantir a sobrevivência individual e das suas famílias.

Extracção de areia na Praia de Calhetona (Ilha de Santiago, Cabo Verde) : causas, processos e consequências

A extracção de areia nas praias do mar, nas bacias hidrográficas e nas encostas montanhosas, tem sido prática de muitas famílias cabo-verdianas. A Praia de Calhetona foi uma das que nos últimos anos sofreu degradação significativa, em função da apanha clandestina de areia, sem qualquer plano de extracção, destinada a construção civil. A extracção de areia, para vender ou para a autoconstrução, é efectuada em família por indivíduos, maioritariamente do sexo feminino, de baixa renda ou sem profissão remunerada. O processo de extracção de areia na Praia de Calhetona teve o seu ponto alto nos anos 80, diminuindo consideravelmente com a escassez de areia e implementação do Decreto – Lei nº 69/97, de 3 de Novembro, que visava disciplinar a exploração de inertes nas praias. Em face da pesquisa feita, baseada no estudo de caso, ficou expresso que os inquiridos implicados na actividade de extracção clandestina de areia correm riscos elevados para obterem lucros reduzidos. Quem efectivamente beneficia são os camionistas que compram esse inerte e o vendem pelo dobro do preço. Qualquer actividade de exploração de recursos naturais causa impactes sobre o espaço de actuação. No caso da Praia de Calhetona, observa-se o recuo da linha de costa, a quase ausência de areia e a desertificação de propriedades nas suas proximidades, para além dos impactes negativos sobre o turismo, a função balnear e a desova de tartaruga. Apesar de tudo, constata-se uma consciência generalizada dos impactes ambientais causados pelos inquiridos, os quais, no entanto, alegam que a extracção de areia é uma das alternativas para garantir a sobrevivência individual e das suas famílias.

Extracção de areia na Praia de Calhetona (Ilha de Santiago, Cabo Verde) : causas, processos e consequências

A extracção de areia nas praias do mar, nas bacias hidrográficas e nas encostas montanhosas, tem sido prática de muitas famílias cabo-verdianas. A Praia de Calhetona foi uma das que nos últimos anos sofreu degradação significativa, em função da apanha clandestina de areia, sem qualquer plano de extracção, destinada a construção civil. A extracção de areia, para vender ou para a autoconstrução, é efectuada em família por indivíduos, maioritariamente do sexo feminino, de baixa renda ou sem profissão remunerada. O processo de extracção de areia na Praia de Calhetona teve o seu ponto alto nos anos 80, diminuindo consideravelmente com a escassez de areia e implementação do Decreto – Lei nº 69/97, de 3 de Novembro, que visava disciplinar a exploração de inertes nas praias. Em face da pesquisa feita, baseada no estudo de caso, ficou expresso que os inquiridos implicados na actividade de extracção clandestina de areia correm riscos elevados para obterem lucros reduzidos. Quem efectivamente beneficia são os camionistas que compram esse inerte e o vendem pelo dobro do preço. Qualquer actividade de exploração de recursos naturais causa impactes sobre o espaço de actuação. No caso da Praia de Calhetona, observa-se o recuo da linha de costa, a quase ausência de areia e a desertificação de propriedades nas suas proximidades, para além dos impactes negativos sobre o turismo, a função balnear e a desova de tartaruga. Apesar de tudo, constata-se uma consciência generalizada dos impactes ambientais causados pelos inquiridos, os quais, no entanto, alegam que a extracção de areia é uma das alternativas para garantir a sobrevivência individual e das suas famílias.

Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress.

Active protein-disaggregation by a chaperone network composed of ClpB and DnaK + DnaJ + GrpE is essential for the recovery of stress-induced protein aggregates in vitro and in Escherichia coli cells. K-glutamate and glycine-betaine (betaine) naturally accumulate in salt-stressed cells. In addition to providing thermo-protection to native proteins, we found that these osmolytes can strongly and specifically activate ClpB, resulting in an increased efficiency of chaperone-mediated protein disaggregation. Moreover, factors that inhibited the chaperone network by impairing the stability of the ClpB oligomer, such as natural polyamines, dilution, or high salt, were efficiently counteracted by K-glutamate or betaine. The combined protective, counter-negative and net activatory effects of K-glutamate and betaine, allowed protein disaggregation and refolding under heat-shock temperatures that otherwise cause protein aggregation in vitro and in the cell. Mesophilic organisms may thus benefit from a thermotolerant osmolyte-activated chaperone mechanism that can actively rescue protein aggregates, correctly refold and maintain them in a native state under heat-shock conditions.

Abnormal balance between proliferation and apoptotic cell death in fibroblasts derived from keloid lesions.

A new culture model was developed to study the role of proliferation and apoptosis in the etiology of keloids. Fibroblasts were isolated from the superficial, central, and basal regions of six different keloid lesions by using Dulbecco's Modified Eagle Medium containing 10% fetal calf serum as a culture medium. The growth behavior of each fibroblast fraction was examined in short-term and long-term cultures, and the percentage of apoptotic cells was assessed by in situ end labeling of fragmented DNA. The fibroblasts obtained from the superficial and basal regions of keloid tissue showed population doubling times and saturation densities that were similar to those of age-matched normal fibroblasts. In contrast, the fibroblasts from the center of the keloid lesions showed significantly reduced doubling times (25.9 +/- 6.3 hours versus 43.5 +/- 6.3 hours for normal fibroblasts) and reached higher cell densities. In long-term culture, central keloid fibroblasts formed a stratified three-dimensional structure, contracted the self-produced extracellular matrix, and gave rise to nodular cell aggregates, mimicking the formation of keloid tissue. Apoptotic cells were detected in both normal and keloid-derived fibroblasts, but their numbers were twofold higher in normal cells compared with all keloid fibroblasts. To examine whether apoptosis mediates the therapeutic effect of ionizing radiation on keloids, the cells were exposed to gamma rays at a dose of 8 Gy. Under these conditions, a twofold increase in the population of apoptotic cells was detected. These results indicate that the balance between proliferation and apoptosis is impaired in keloid fibroblasts, which could be responsible for the formation of keloid tumors. The results also suggest that keloids contain at least two different fibroblast fractions that vary in growth behavior and extracellular matrix metabolism.

Extracção de Areia na Praia de Calhetona (Ilha de Santiago, Cabo Verde) - Causas, Processos e Consequências

A extracção de areia nas praias do mar, nas bacias hidrográficas e nas encostas montanhosas, tem sido prática de muitas famílias cabo-verdianas. A Praia de Calhetona foi uma das que nos últimos anos sofreu degradação significativa, em função da apanha clandestina de areia, sem qualquer plano de extracção, destinada a construção civil. A extracção de areia, para vender ou para a autoconstrução, é efectuada em família por indivíduos, maioritariamente do sexo feminino, de baixa renda ou sem profissão remunerada. O processo de extracção de areia na Praia de Calhetona teve o seu ponto alto nos anos 80, diminuindo consideravelmente com a escassez de areia e implementação do Decreto – Lei nº 69/97, de 3 de Novembro, que visava disciplinar a exploração de inertes nas praias. Em face da pesquisa feita, baseada no estudo de caso, ficou expresso que os inquiridos implicados na actividade de extracção clandestina de areia correm riscos elevados para obterem lucros reduzidos. Quem efectivamente beneficia são os camionistas que compram esse inerte e o vendem pelo dobro do preço. Qualquer actividade de exploração de recursos naturais causa impactes sobre o espaço de actuação. No caso da Praia de Calhetona, observa-se o recuo da linha de costa, a quase ausência de areia e a desertificação de propriedades nas suas proximidades, para além dos impactes negativos sobre o turismo, a função balnear e a desova de tartaruga. Apesar de tudo, constata-se uma consciência generalizada dos impactes ambientais causados pelos inquiridos, os quais, no entanto, alegam que a extracção de areia é uma das alternativas para garantir a sobrevivência individual e das suas famílias.

Identification of an agrin mutation that causes congenital myasthenia and affects synapse function.

We report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. Gene analysis identified a homozygous missense mutation, c.5125G>C, leading to the p.Gly1709Arg variant. The muscle-biopsy specimen showed a major disorganization of the neuromuscular junction, including changes in the nerve-terminal cytoskeleton and fragmentation of the synaptic gutters. Experiments performed in nonmuscle cells or in cultured C2C12 myotubes and using recombinant mini-agrin for the mutated and the wild-type forms showed that the mutated form did not impair the activation of MuSK or change the total number of induced acetylcholine receptor aggregates. A solid-phase assay using the dystrophin glycoprotein complex showed that the mutation did not affect the binding of agrin to alpha-dystroglycan. Injection of wild-type or mutated agrin into rat soleus muscle induced the formation of nonsynaptic acetylcholine receptor clusters, but the mutant protein specifically destabilized the endogenous neuromuscular junctions. Importantly, the changes observed in rat muscle injected with mutant agrin recapitulated the pre- and post-synaptic modifications observed in the patient. These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction.

Dessalinização da Água do Mar Através da Energia Solar - Caso de Estudo Salamansa – Cabo Verde

principal objectivo deste trabalho é o estudo da viabilidade técnica e económica da dessalinização da água do mar, utilizando a energia solar, tomando como caso de aplicação uma pequena comunidade rural de Cabo Verde, a vila piscatória de Salamansa, local onde há graves problemas com a disponibilidade de água potável. No entanto, a proximidade do mar e a disponibilidade de energia solar sugerem a dessalinização como processo para mitigar a falta de água. A dessalinização da água do mar pode ser obtida através de diversas técnicas que podem ser agrupadas de acordo com os princípios em que estes processos se baseiam: processos de dessalinização térmica (destilação solar, destilação multi-estágio, destilação multi-efeito, etc.) e processos de dessalinização por membranas (electrodiálise e osmose inversa). A destilação solar passiva foi a tecnologia de dessalinização estudada neste trabalho e que se pode vir a tornar uma alternativa promissora para um fornecimento regular de água. Por outro lado, o uso de fontes alternativas de energia, como a solar, apresenta-se como uma solução para viabilizar a dessalinização em meios semi-áridos como o deste caso de estudo. Fez-se uma modelação matemática da unidade de destilação solar proposta utilizando o Engineering Equation Solver (EES) como ferramenta para ajudar a resolver as equações de balanço térmico. O projecto do destilador solar proposto poderá atender às necessidades de água doce para consumo de 18 famílias constituídas por 5 agregados (92 pessoas) e apresenta uma eficiência média diária de aproximadamente 78% no Verão e 77% no Inverno.

Association of nuclear matrix proteins with granular and threaded nuclear bodies in cell lines undergoing apoptosis.

The granules which appear in the nucleolar area in apoptotic HL-60 cells after camptothecin administration (Zweyer et al., Exp. Cell Res. 221,27-40, 1995) were detected also in several other cell lines induced to undergo apoptosis by different stimuli, such as MOLT-4 treated with staurosporine, K-562 incubated with actinomycin D, P-815 exposed to temperature causing heat shock, Jurkat cells treated with EGTA, U-937 growing in the presence of cycloheximide and tumor necrosis factor-alpha, and HeLa cells treated with etoposide. Using immunoelectron microscopy techniques, we demonstrate that, besides the already described nuclear matrix proteins p125 and p160, these granules contain other nucleoskeletal polypeptides such as proliferating cell nuclear antigen, a component of ribonucleoprotein particles, a 105-kDa constituent of nuclear spliceosomes, and the 240-kDa nuclear mitotic apparatus-associated protein referred to as NuMA. Moreover, we also found in the granules SAF-A/hn-RNP-U and SATB1 proteins, two polypeptides that have been reported to bind scaffold-associated regions DNA sequences in vitro, thus mediating the formation of looped DNA structures in vivo. Fibrillarin and coilin are not present in these granules or the PML protein. Thus, the granules seen during the apoptotic process apparently are different from coiled bodies or other types of nuclear bodies. Furthermore, these granules do not contain chromatin components such as histones and DNA. Last, Western blotting analysis revealed that nuclear matrix proteins present in the granules are not proteolytically degraded except for the NuMA polypeptide. We propose that these granules might represent aggregates of nuclear matrix proteins forming during the apoptotic process. Moreover, since the granules are present in several cell lines undergoing apoptosis, they could be considered a previously unrecognized morphological hallmark of the apoptotic process.

Forecasting the effects of global warming on biodiversity

The demand for accurate forecasting of the effects of global warming on biodiversity is growing, but current methods for forecasting have limitations. in this article, we compare and discuss the different uses of four forecasting methods: (1) models that consider species individually, (2) niche-theory models that group species by habitat (more specifically, by environmental conditions under which a species can persist or does persist), (3) general circulation models and coupled ocean-atmosphere-biosphere models, and (4) specics-area curve models that consider all species or large aggregates of species. After outlining the different uses and limitations of these methods, we make eight primary suggestions for improving forecasts. We find that greater use of the fossil record and of modern genetic studies would improve forecasting methods. We note a Quaternary conundrum: While current empirical and theoretical ecological results suggest that many species could be at risk from global warming, during the recent ice ages surprisingly few species became extinct. The potential resolution of this conundrum gives insights into the requirements for more accurate and reliable forecasting. Our eight suggestions also point to constructive synergies in the solution to the different problems.

Avaluació dels recursos d'àrids disponibles en medis fluvials mitjançant tècniques geofisiques. Aplicació a la cubeta de Celrà (Riu Ter, Ne Catalunya)

The depth of the water table and the clay content are determinant factors for the exploitability of natural aggregates, such as the alluvial sands and gravels found on the fluvial domain of the Ter River. In this preliminary study, carried out in the Celri basin, we conclude that these variables can be determined by means of geophysical methods and recornmends the use of such methods in studies of regional character

Iron oxides in plinthic soils on sedimentary deposits in northeastern Brazil

This study was conducted to examine the distribution and nature of Fe oxides in plinthic soils on the sediments of Barreiras Group (in the state of Piauí) and Itapecuru Formation (in the state of Maranhão) in Northeastern Brazil. Four pedons were selected: a "plinthic, dystrophic, epieutrophic Gray Podzolic with low activity clay" and a "dystrophic Plinthosol with low activity clay" (both Plinthic Kandiustalfs) on the Barreiras sediments, as well as an "eutrophic Plinthosol with low activity clay" and an "allic Plinthosol with low activity clay" (both Plinthustalfs) on the Itapecuru sediments. Soil samples were fractionated into > 2 mm (pisoliths), water-stable aggregates (plinthite) and matrices; the aggregates and matrices were further fractionated into sand, silt and clay sizes. Dithionite extractable iron (Fe d) and aluminum (Al d), as well as oxalate extractable iron (Fe o), were determined for all fractions, and X-ray diffraction analyses were performed on the pisoliths. It was observed that the Plinthustalfs contain more iron oxides, exhibit more extensive plinthite development and have a greater potential for further plinthite development than the Kandiustalfs. The distribution of values for the Fe d indicates that plinthite formation and induration in all soils were accompanied by an enrichment of Fe oxides in all particle size fractions. This Fe segregation was accompanied by aggregation of particles leading to a greater degree of crystallinity, as indicated by analysis of the ratios of Al d:Fe d. Larger ratios of goethite to hematite, and relatively smaller amounts of silicates in the more mature pisoliths were revealed by X-ray diffraction analysis. Ratios of Al d:Fe d were larger in the Kandiustalfs than in the Plinthustalfs, and also larger than expected for Al-substituted Fe oxides. According to ratios of Al d:Fe d, Fe mobilization in all soils has likely occurred under reducing conditions, facilitated by organic matter on the soil surface.

Structure-function characterization and optimization of a plant-derived antibacterial peptide.

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.