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Showing papers by "University of Lisbon published in 2000"


Journal ArticleDOI
TL;DR: This article attempts to provide useful insights on the linkages between innovation and competitiveness by considering how knowledge development is related with personal characteristics and personal development.
Abstract: Is concerned with human value management, examines the relationships between organizations’ competitiveness, innovation advancements, and knowledge management and presents a set of considerations regarding how these relationships affect strategic management and the formulation of competitive strategies. By considering how knowledge development is related with personal characteristics and personal development, this article attempts to provide useful insights on the linkages between innovation and competitiveness. These considerations point out the importance of knowledge development and the role of knowledge management in order to assure competitiveness. This work proposes also a conceptual model, with special focus on the relationships between knowledge management, competitiveness, and innovation. The major factors are presented and directions for future research are suggested according to the proposed model.

609 citations


Journal ArticleDOI
TL;DR: In this paper, an objective classification scheme of the atmospheric circulation affecting Portugal, between 1946 and 1990, is presented, where daily circulation is characterized through the use of a set of indices associated with the direction and vorticity of the geostrophic flow.
Abstract: An objective classification scheme of the atmospheric circulation affecting Portugal, between 1946 and 1990, is presented, where daily circulation is characterized through the use of a set of indices associated with the direction and vorticity of the geostrophic flow. The synoptic characteristics and the frequency of ten basic circulation weather types (CWTs) are discussed, as well as the amount of precipitation associated with each type between 1957 and 1986. It is shown that the anticyclonic (A) type, although being the most frequent class in winter (37%), gives a rather small (less then 16%) contribution to the winter precipitation amount, observed on a daily basis. On the other hand, the three wettest CWTs, namely the cyclonic (C), southwesterly (SW) and westerly (W) types, together representing only 32% of all winter days, account for more than 62% of the observed daily precipitation. Results obtained highlight the existence of strong links between the interannual variability of monthly precipitation and interannual variability of CWTs. Multiple regression models, developed for 18 stations, show the ability of modelling monthly winter precipitation through the exclusive use, as predictors, of the wet CWTs (i.e. C, SW and W). The observed decreasing trend of March precipitation is also analysed and shown to be especially associated with the decrease of the three wet weather types. The anomalous low (high) frequency of wet CWTs during the hydrological year is shown to be strongly related with the occurrence of extreme dry (wet) years in Portugal, which had important impacts on Portuguese agriculture. Overall, the results suggest that the precipitation regime over Portugal, including interannual variability, trends and extremes, may be adequately explained in terms of variability of a fairly small number of circulation weather patterns. On the other hand, observed contrasts in the spatial distribution of correlations between frequency of wet CWTs and rainfall amounts suggest that precipitation regimes are of a different nature in northern and southern regions of Portugal; the former possessing an orographic origin and the latter being associated to cyclogenetic activity. Copyright © 2000 Royal Meteorological Society.

439 citations


Journal ArticleDOI
TL;DR: The emerging view is that molecular confinement in the nucleolus actively contributes to the control of cellular survival and proliferation.
Abstract: Compartmentalization has long been known to have a key role in regulation of cellular processes. By keeping enzymes and regulatory complexes in compartments where the delivery of substrate or exit of product is controlled, competing reactions can occur simultaneously in different parts of the cell. Moreover, spatial confinement facilitates the working of molecules participating in reaction chains and is crucial for coupling unfavourable with energetically favourable chemical reactions. Although in many cases intracellular compartmentalization relies on boundaries imposed by membranes, several non-membrane-bounded compartments exist in eukaryotic cells. One of these, the nucleolus, has recently attracted much attention. The emerging view is that molecular confinement in the nucleolus actively contributes to the control of cellular survival and proliferation.

397 citations


Journal ArticleDOI
01 Jan 2000-RNA
TL;DR: The interaction of TAP with nucleoporins, its direct binding to the CTE RNA, and its association with two mRNP binding proteins suggest that TAP is an RNA export mediator that may bridge the interaction between specific RNP export substrates and the NPC.
Abstract: Messenger RNAs are exported from the nucleus as large ribonucleoprotein complexes (mRNPs). To date, proteins implicated in this process include TAP/Mex67p and RAE1/Gle2p and are distinct from the nuclear transport receptors of the beta-related, Ran-binding protein family. Mex67p is essential for mRNA export in yeast. Its vertebrate homolog TAP has been implicated in the export of cellular mRNAs and of simian type D viral RNAs bearing the constitutive transport element (CTE). Here we show that TAP is predominantly localized in the nucleoplasm and at both the nucleoplasmic and cytoplasmic faces of the nuclear pore complex (NPC). TAP interacts with multiple components of the NPC including the nucleoporins CAN, Nup98, Nup153, p62, and with three major NPC subcomplexes. The nucleoporin-binding domain of TAP comprises residues 508-619. In HeLa cells, this domain is necessary and sufficient to target GFP-TAP fusions to the nuclear rim. Moreover, the isolated domain strongly competes multiple export pathways in vivo, probably by blocking binding sites on the NPC that are shared with other transport receptors. Microinjection experiments implicate this domain in the export of specific CTE-containing RNAs. Finally, we show that TAP interacts with transportin and with two proteins implicated in the export of cellular mRNAs: RAE1/hGle2 and E1B-AP5. The interaction of TAP with nucleoporins, its direct binding to the CTE RNA, and its association with two mRNP binding proteins suggest that TAP is an RNA export mediator that may bridge the interaction between specific RNP export substrates and the NPC.

332 citations


Journal ArticleDOI
TL;DR: It is demonstrated that VSV M inhibits host cell gene expression by targeting a nucleoporin and primarily blocking nuclear export.

263 citations


Journal ArticleDOI
TL;DR: In this article, the authors evaluated the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-infected patients first starting protease inhibitor or non-nucleoside retrotranscriptase inhibitor-containing antiretroviral therapy in Europe.
Abstract: Background Predictors of virological response to highly active antiretroviral therapy (HAART) have never been systematically evaluated in a large continental multicenter cohort of unselected human immunodeficiency virus (HIV)–infected people. Objective To determine the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-1–infected patients first starting protease inhibitor– or nonnucleoside retrotranscriptase inhibitor–containing HAART in Europe. Design Prospective multicenter cohort study. Setting Fifty-two clinical centers in 17 European countries included in the EuroSIDA Study Group, from August 1996 to April 1999. Patients A total of 1469 HIV-positive patients first starting HAART recruited from an unselected cohort of more than 7300 HIV-positive patients. Main Outcome Measure Detection of factors related to virological success after first starting HAART (baseline) and ensuing failure by standard survival techniques, including Kaplan-Meier techniques and Cox proportional hazards models. All analyses were intention to treat. Results Most patients (80%) achieved plasma HIV-1 RNA levels of less than 500 copies/mL during follow-up (60.4% at 6 months from the onset of HAART). Patients with higher baseline HIV-1 RNA levels (relative hazard [RH], 0.76 per log higher; 95% confidence interval [CI], 0.69-0.84; P P + lymphocyte counts (RH per 50% higher, 1.09; 95% CI, 1.02-1.16; P =.008) and the initiation of 3 or more new antiretroviral drugs (RH, 1.29; 95% CI, 1.03-1.61; P =.02) were independent predictors of higher success. Once success was achieved, HIV-1 RNA levels rebounded in more than one third of all patients during follow-up (24% at 6 months). Antiretroviral-naive patients (RH, 0.50; 95% CI, 0.29-0.87; P =.01), older patients (RH, 0.86 per year older; 95% CI, 0.75-0.99; P =.04), and those starting a protease inhibitor other than saquinavir hard gel (RH, 0.66; 95% CI, 0.44-0.98; P =.04) were at decreased hazard for virological failure. Higher baseline HIV-1 RNA level (RH, 1.18 per log higher; 95% CI, 0.99-1.40; P =.06) and a longer time to achieve virological success (RH per 12 months, 1.53; 95% CI, 0.99-2.38; P =.06) were marginally significant predictors of a decreased hazard of ensuing virological failure. Conclusions HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor. Older patients are more likely to achieve virological success. Thereafter, the higher durability of virological response is predicted by an antiretroviral-naive status and by the use of specific regimens. Lower baseline HIV-1 RNA levels and rapid maximal viral suppression seem to be other important factors in the durability of virological response.

253 citations


Journal ArticleDOI
TL;DR: In this article, the AIM approach, by analyzing the topological properties of the charge density with the determination of critical points, provides another way of looking for bonds, as discussed in several examples.

250 citations


Journal ArticleDOI
J. Alcaraz, Behcet Alpat, Giovanni Ambrosi, H. Anderhub1  +199 moreInstitutions (20)
TL;DR: The lepton kinetic energy ranges from 0.2 to 40 GeV for e − and from 3 GeV to 6 GeVs for e + were measured by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at altitudes near 380 km.

248 citations


Journal ArticleDOI
TL;DR: The results indicate that the TAP-p15 mRNA export pathway has diversified in higher eukaryotes compared to yeast, perhaps reflecting a greater substrate complexity.
Abstract: Vertebrate TAP (also called NXF1) and its yeast orthologue, Mex67p, have been implicated in the export of mRNAs from the nucleus. The TAP protein includes a noncanonical RNP-type RNA binding domain, four leucine-rich repeats, an NTF2-like domain that allows heterodimerization with p15 (also called NXT1), and a ubiquitin-associated domain that mediates the interaction with nucleoporins. Here we show that TAP belongs to an evolutionarily conserved family of proteins that has more than one member in higher eukaryotes. Not only the overall domain organization but also residues important for p15 and nucleoporin interaction are conserved in most family members. We characterize two of four human TAP homologues and show that one of them, NXF2, binds RNA, localizes to the nuclear envelope, and exhibits RNA export activity. NXF3, which does not bind RNA or localize to the nuclear rim, has no RNA export activity. Database searches revealed that although only one p15 (nxt) gene is present in the Drosophila melanogaster and Caenorhabditis elegans genomes, there is at least one additional p15 homologue (p15-2 [also called NXT2]) encoded by the human genome. Both human p15 homologues bind TAP, NXF2, and NXF3. Together, our results indicate that the TAP-p15 mRNA export pathway has diversified in higher eukaryotes compared to yeast, perhaps reflecting a greater substrate complexity.

232 citations


Journal ArticleDOI
TL;DR: It is reported that PABP2 is detected in filamentous nuclear inclusions, which are the pathological hallmark of OPMD, and the inclusions were labeled with antibodies directed against ubiquitin and the subunits of the proteasome and contained a form of P ABP2 that was more resistant to salt extraction than the protein dispersed in the nucleoplasm.
Abstract: Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. The autosomal dominant form of the disease is caused by short (GCG)8–13 expansions in the PABP2 gene. This gene encodes the poly(A) binding protein 2 (PABP2), an abundant nuclear protein that binds with high affinity to nascent poly(A) tails, stimulating their extension and controlling their length. I nt his work we report that PABP2 is detected in filamentous nuclear inclusions, which are the pathological hallmark of OPMD. Using both immunoelectron microscopy and fluorescence confocal microscopy, the OPMD-specific nuclear inclusions appeared decorated by anti-PABP2 antibodies. In addition, the inclusions were labeled with antibodies directed against ubiquitin and the subunits of the proteasome and contained a form of PABP2 that was more resistant to salt extraction than the protein dispersed in the nucleoplasm. This suggests that the polyalanine expansions in PABP2 induce a misfolding and aggregation of the protein into insoluble inclusions, similarly to events in neurodegenerative diseases caused by CAG/polyglutamine expansions. No significant differences were observed in the steady-state poly(A) tail length in OPMD and normal myoblasts. However, the nuclear inclusions were shown to sequester poly(A) RNA. This raises the possibility that in OPMD the polyalanine expansions in the PABP2 protein may interfere with the cellular traffic of poly(A) RNA.

229 citations


Journal ArticleDOI
TL;DR: In this article, the computation of normal forms for Partial Functional Differential Equations (PFDEs) near equilibria has been studied and the analysis is based on the theory previously developed for autonomous functional differential equations and on the existence of center (or other invariant) manifold.
Abstract: The paper addresses the computation of normal forms for some Partial Functional Differential Equations (PFDEs) near equilibria. The analysis is based on the theory previously developed for autonomous retarded Functional Differential Equations and on the existence of center (or other invariant) manifolds. As an illustration of this procedure, two examples of PFDEs where a Hopf singularity occurs on the center manifold are considered.

Journal ArticleDOI
TL;DR: In this article, the authors describe the structure of subdirectly irreducible hoops, and establish that the class of hoops is generated, as a quasivariety, by its finite members.
Abstract: A hoop is a naturally ordered pocrim (ie, a partially ordered commutative residuated integral monoid) We list some basic properties of hoops, describe in detail the structure of subdirectly irreducible hoops, and establish that the class of hoops, which is a variety, is generated, as a quasivariety, by its finite members

Journal ArticleDOI
TL;DR: Evidence is reviewed to suggest that ATP may also act presynaptically rather than solely postsynaptically in the nervous system.

Journal ArticleDOI
TL;DR: Pollen tubes may serve as a powerful model for exploring the basis of cell growth and morphogenesis and unite experimental simplicity with clear oscillatory patterns of both structural and temporal features.
Abstract: Summary The occurrence of oscillatory behaviours in living cells can be viewed as a visible consequence of stable, regulatory homeostatic cycles. Therefore, they may be used as experimental windows on the underlying physiological mechanisms. Recent studies show that growing pollen tubes are an excellent biological model for these purposes. They unite experimental simplicity with clear oscillatory patterns of both structural and temporal features, most being measurable during real-time in live cells. There is evidence that these cellular oscillators involve an integrated input of plasma membrane ion fluxes, and a cytosolic choreography of protons, calcium and, most likely, potassium and chloride. In turn, these can create positive feedback regulation loops that are able to generate and self-sustain a number of spatial and temporal patterns. Other features, including cell wall assembly and rheology, turgor, and the cytoskeleton, play important roles and are targets or modulators of ion dynamics. Many of these features have similarities with other cell types, notably with apical-growing cells. Pollen tubes may thus serve as a powerful model for exploring the basis of cell growth and morphogenesis. BioEssays 23:86‐94, 2001. fl 2001 John Wiley & Sons, Inc.

Journal ArticleDOI
TL;DR: When relatives of patients with schizophrenia are able to improve their coping strategies, it is possible for burden to be reduced even after several years, and this points to the necessity to provide families of chronic psychotic patients with psychoeducational interventions emphasising the adoption of an effective coping style.
Abstract: Background: To date, only few data are available on how family burden in schizophrenia changes over time. In addition, no study has explored how such factors as coping styles and social support influence burden over time. This paper presents the 1-year follow-up data from the BIOMED I study on family burden and coping strategies in schizophrenia. Methods: A sample of 159 relatives of patients with schizophrenia living in five European countries was followed up prospectively for 1 year with regard to burden and coping strategies, using validated questionnaires. Results: In the sample as a whole, the burden was stable. A reduction of family burden over time was found among relatives who adopted less emotion-focused coping strategies and received more practical support from their social network. In addition, family burden decreased in relation to the improvement of patient's social functioning. Conclusions: When relatives of patients with schizophrenia are able to improve their coping strategies, it is possible for burden to be reduced even after several years. This points to the necessity to provide families of chronic psychotic patients with psychoeducational interventions emphasising the adoption of an effective coping style.

Book ChapterDOI
TL;DR: The geological setting and vent fluid composition of the fields are considered together with their community composition to tentatively ascertain the order of a hierarchy between dispersal and environmental control, suggesting faunal islands that have distinct composition and habitat requirements.
Abstract: Until 1985, seven vent fields were described from the Mid-Atlantic Ridge (MAR). An eighth field, Mount Saldanha (36° N), discovered in 1998, showed unusual geological and biological settings. Vent sites on the MAR exhibit varied environmental conditions, resulting from depth variation of the axis and associated physical parameters, and different source rocks. These could be considered as first order (i.e. most dominant) factors affecting the composition of vent communities on the MAR, in contrast to the East Pacific Rise (EPR) where geographical isolation appears to be a major determinant of faunal differences. In this paper, the geological setting and vent fluid composition of the fields are considered together with their community composition to tentatively ascertain the order of a hierarchy between dispersal and environmental control. The deepest fields (>3000 m) are rather stable systems. The shallower fields, especially Rainbow and Menez Gwen, present some evidence of instability in time and space. The variability in fluid composition is related to phase separation processes (boiling/distillation of subsurface vent fluids) and to the nature of the basement rocks. Depending on depth, phase separation produces gas-enriched and metal-depleted fluids (Menez Gwen, Lucky Strike) or metal-enriched brines (Rainbow, TAG). In addition, high methane content characterises the fluids formed in ultramafic rocks (Rainbow, Logatchev) compared to basaltic rocks. The discrepancy in mineral particulate fluxes at Lucky Strike and Menez Gwen, on one hand, and TAG and Rainbow, on the other, is correlated to the predominance of the vapour or brine phase. The semi-quantitative description of the faunal composition of the different vent fields displays a continuum from Rimicaris-dominated to Bathymodiolus-dominated assemblages. Rather than geographic or bathymetric zonation, this gradation appears to be related to the metal content of the fluids. In addition, the penetration of non vent species into the vent environment increases with decreasing hydrostatic pressure and/or metal content in the fluids. Similarity analysis between vent communities shows that similarity is strongest between Menez Gwen and Lucky Strike (the shallowest fields), less significant between these sites and Rainbow, and weakest for Snake Pit. The inverse relationship between filter feeding organisms and metal concentration in vent fluids could result from a hindrance of mussel bed development by particulate or toxic metal fluxes, and has to be further investigated. Conversely, high metal and particulate content would less affect the more mobile Rimicaris populations. Considering specific similarities of endemic fauna between the four best known hydrothermal vents, the distance between vent fields appears to be a first order parameter. Nevertheless, within the proximity of the Azores Triple Junction area, and in the absence of geographical discontinuity, the similarity between fields stays rather low suggesting faunal islands that have distinct composition and habitat requirements.

Journal ArticleDOI
TL;DR: In this article, the relativistic and non-relativistic binary-encounter-dipole (BEB) models were extended to relativistically incident electron energies.
Abstract: Formulas for the total ionization cross section by electron impact based on the binary-encounter-dipole (BED) model and its simpler version, the binary-encounter-Bethe (BEB) model are extended to relativistic incident electron energies. Total ionization cross sections for the hydrogen and helium atoms from the new relativistic formulas are compared to experimental data. Relativistic effects double the total ionization cross section of H and He at incident electron energy $\ensuremath{\approx}300 \mathrm{keV}$ and dominate the cross section thereafter. A simple modification of the original BED-BEB formulas is proposed for applications to ion targets and inner-shell electrons of neutral atoms and molecules. The relativistic and nonrelativistic BEB cross sections are compared to the K-shell ionization cross sections by electron impact for the carbon, argon, nickel, niobium, and silver atoms. For carbon and argon, the relativistic effects are small, and both forms of the BEB cross sections agree well with available experimental data. For the nickel and heavier atoms, the relativistic increase of cross sections becomes noticeable from about 100 keV and higher in the incident electron energy. The empirical formula by Casnati et al. [J. Phys. B 15, 155 (1982)] after correcting for relativistic effects as shown by Quarles [Phys. Rev. A 13, 1278 (1976)] agrees well with the BEB cross sections for light atoms. However, the peak values of the Casnati cross sections become higher than the relativistic BEB peak cross sections as the atomic number increases. The BEB model is also applied to the total ionization cross section of the xenon atom, and the theory agrees well with experiments at low incident electron energies, but disagrees with experiment at relativistic incident energies.

Journal ArticleDOI
TL;DR: In this article, the present understanding of how dipolar forces affect the structure and phase behaviour of classical fluids is reviewed, focusing mainly on the apparent absence of a liquid-vapour phase transition for strongly polar spherical particles and discuss how the same can be recovered.
Abstract: The present understanding of how dipolar forces affect the structure and phase behaviour of classical fluids is reviewed. We focus mainly on the apparent absence of a liquid-vapour phase transition for strongly polar spherical particles, and discuss how the same can be recovered. By concentrating on theoretical and simulation studies of simple models, the roles and interplay of dipolar and Van der Waals interactions and molecular shape can be clearly discerned. Connection is made with experimental work on ferrofluids. Finally, we discuss the theoretical and computational challenges that lie ahead.

Journal ArticleDOI
TL;DR: In this article, the authors examine the role that big cities play in an ongoing change towards a 'global cultural economy' starting from Allen Scott's argument that a handful of urban flagships may benefit from...
Abstract: This article examines the role that big cities play in an ongoing change towards a ‘global cultural economy’. Starting from Allen Scott’s argument that a handful of urban flagships may benefit from...

Journal ArticleDOI
TL;DR: In this paper, the authors examined the traditional interpretation of Coccolithus pelagicus as a cold water proxy based on its distribution patterns in the water column off the Portuguese coast (using data from eleven cruises) and in Holocene surface sediment samples and Quaternary cores from the same region.

Journal ArticleDOI
TL;DR: It was concluded that H. portulacoides is a more effective accumulator of metals than S. maritima, and both root-sediment systems exhibited a seasonal variation of metal concentrations.

Book ChapterDOI
01 Jan 2000
TL;DR: In this article, a rewiew paper summarizes some results and applications concerning first and second order sweeping processes, starting from an elementary level, and summarizing some results, applications, and results.
Abstract: Starting from an elementary level, this rewiew paper summarizes some results and applications concerning first and second order sweeping processes.

Journal ArticleDOI
TL;DR: In this paper, the authors discuss contravariant connections on Poisson manifolds and show that these connections play an important role in the study of global properties of Poisson manifold, and use them to define Poisson holonomy and new invariants.
Abstract: We discuss contravariant connections on Poisson manifolds. For vector bun­ dles, the corresponding operational notion of a contravariant derivative had been introduced by I. Vaisman. We show that these connections play an important role in the study of global properties of Poisson manifolds and we use them to define Poisson holonomy and new invariants of Poisson manifolds.

Journal ArticleDOI
TL;DR: It is shown that the Drosophila kinetochore components Rough deal (Rod) and Zeste-White 10 (Zw10) are required for the proper functioning of the metaphase checkpoint in flies, the first checkpoint components to be identified that do not have obvious homologues in budding yeast.
Abstract: The metaphase–anaphase transition during mitosis is carefully regulated in order to assure high-fidelity transmission of genetic information to the daughter cells. A surveillance mechanism known as the metaphase checkpoint (or spindle-assembly checkpoint) monitors the attachment of kinetochores to the spindle microtubules, and inhibits anaphase onset until all chromosomes have achieved a proper bipolar orientation on the spindle. Defects in this checkpoint lead to premature anaphase onset, and consequently to greatly increased rates of aneuploidy. Here we show that the Drosophila kinetochore components Rough deal (Rod) and Zeste-White 10 (Zw10) are required for the proper functioning of the metaphase checkpoint in flies. Drosophila cells lacking either ROD or Zw10 exhibit a phenotype that is similar to that of bub1 mutants — they do not arrest in metaphase in response to spindle damage, but instead separate sister chromatids, degrade cyclin B and exit mitosis. These are the first checkpoint components to be identified that do not have obvious homologues in budding yeast.

Journal ArticleDOI
TL;DR: For both species, the importance of larger prey items in the diet, namely H. diversicolor and Crangon crangon, increased with fish size.
Abstract: Among the stomach contents of 609 individuals of Solea solea and 1104 of S. senegalensis the main food items of S. solea were Corophium spp. and Hediste diversicolor, and of S. senegalensis were Corophium spp., H. diversicolor and Scrobicularia plana. For both species, the importance of larger prey items in the diet, namely H. diversicolor and Crangon crangon, increased with fish size. Feeding activity of S. solea and S senegalensis increased in spring and summer. Short-term variations were particularly related to the tidal cycle and the two species fed in intertidal areas. Dietary differences between the two nursery areas reflected prey availability mainly. Although intra- and interspecific length classes overlapped in diet, potential interspecific competition was probably minimized by a differential habitat use pattern.

Journal ArticleDOI
TL;DR: The present results demonstrated the involvement of NO on DNA damage leading to cell death, and point to a potential role of NO as a signal molecule in these plants.
Abstract: Leaves and callus of Kalanchoe daigremontiana and Taxus brevifolia were used to investigate nitric oxide-induced apoptosis in plant cells. The effect of nitric oxide (NO) was studied by using a NO donor, sodium nitroprusside (SNP), a nitric oxide-synthase (NOS) inhibitor, N:(G)-monomethyl-L-arginine (NMMA), and centrifugation (an apoptosis-inducing treatment in these species). NO production was visualized in cells and tissues with a specific probe, diaminofluorescein diacetate (DAF-2 DA). DNA fragmentation was detected in situ by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. In both species, NO was detected diffused in the cytosol of epidermal cells and in chloroplasts of guard cells and leaf parenchyma cells. Centrifugation increased NO production, DNA fragmentation and subsequent cell death by apoptosis. SNP mimicked centrifugation results. NMMA significantly decreased NO production and apoptosis in both species. The inhibitory effect of NMMA on NO production suggests that a putative NOS is present in Kalanchoe and Taxus cells. The present results demonstrated the involvement of NO on DNA damage leading to cell death, and point to a potential role of NO as a signal molecule in these plants.

Journal ArticleDOI
TL;DR: The data suggest that the mitochondria is a pharmacological target for cytoprotection during unconjugated hyperbilirubinemia and neurodegenerative disorders, and that UDC or TUDC may be potential therapeutic agents.
Abstract: BACKGROUND: The pathogenesis of bilirubin encephalopathy and Alzheimer's disease appears to result from accumulation of unconjugated bilirubin (UCB) and amyloid-beta (Abeta) peptide, respectively, which may cause apoptosis Permeabilization of the mitochondrial membrane, with release of intermembrane proteins, has been strongly implicated in cell death Inhibition of the mitochondrial permeability is one pathway by which ursodeoxycholate (UDC) and tauroursodeoxycholate (TUDC) protect against apoptosis in hepatic and nonhepatic cells In this study, we further characterize UCB- and Abeta-induced cytotoxicty in isolated neural cells, and investigate membrane perturbation during incubation of isolated mitochondria with both agents In addition, we evaluate whether the anti-apoptotic drugs UDC and TUDC prevent any changes from occurring MATERIALS AND METHODS: Primary rat neuron and astrocyte cultures were incubated with UCB or Abeta peptide, either alone or in the presence of UDC Apoptosis was assessed by DNA fragmentation and nuclear morphological changes Isolated mitochondria were treated with each toxic, either alone or in combination with UDC, TUDC, or cyclosporine A Mitochondrial swelling was measured spectrophotometrically and cytochrome c protein levels determined by Western blot RESULTS: Incubation of neural cells with both UCB and Abeta induced apoptosis (p 50% (p < 005) Both toxins caused membrane permeabilization in isolated mitochondria (p < 0001); whereas, pretreatment with UDC was protective (p < 005) TUDC was even more effective at preventing matrix swelling mediated by Abeta (p < 001) UDC and TUDC markedly reduced cytochrome c release associated with mitochondrial permeabilization induced by UCB and Abeta, respectively (p < 005) Moreover, cyclosporine A significantly inhibited mitochondrial swelling and cytochrome c efflux mediated by UCB (p < 005) CONCLUSION: UCB and Abeta peptide activate the apoptotic machinery in neural cells Toxicity occurs through a mitochondrial-dependent pathway, which in part involves opening of the permeability transition pore Furthermore, membrane permeabilization is required for cytochrome c release from mitochondria and can be prevented by UDC or TUDC These data suggest that the mitochondria is a pharmacological target for cytoprotection during unconjugated hyperbilirubinemia and neurodegenerative disorders, and that UDC or TUDC may be potential therapeutic agents

Journal ArticleDOI
TL;DR: The adenosine A(2A) receptor system appears to be one of the first presynaptic neuromodulatory systems able to enhance the evoked release of GABA from hippocampal nerve terminals.

Journal ArticleDOI
TL;DR: In this paper, the authors focused on the factors regulating both nitrogen fluxes across the sediment-water interface and denitrification, and on the effect of microphytobenthos activity in controlling nitrogen cycling in these areas.
Abstract: Dissolved nitrogen fluxes and denitrification were studied during 1 yr in intertidal sediments of the Tagus estuary (Portugal). This study focused on the factors regulating both nitrogen fluxes across the sediment-water interface and denitrification, and on the effect of microphytobenthos activity in controlling nitrogen cycling in these areas. Sampling was performed monthly at 2 stations located in inner and outer intertidal areas. Fluxes of O 2 , NO 3 - , NO 2 - , NH 4 + and N 2 O, and denitrification (determined by the nitrogen-isotope pairing technique) were measured simultaneously in closed chambers incubated in the laboratory under simulated in situ temperature and light conditions, as well as in the dark. At the sediment-water interface, higher DIN fluxes and lower denitrification rates were registered at higher temperatures and lower NO 3 - concentration in the water column. Oxygen uptake by the sediment was generally higher than release, particularly in summer. Primary productivity displayed a seasonal cycle, positively influenced by temperature. Denitrification rates were closely related to NO 3 - river-input, Temperature, NO 3 - concentration in the water column, microphytobenthos, infauna and tidal height were the key parameters involved in controlling nitrogen cycling at the sediment-water interface in the Tagus estuary. A comparison of annual nitrogen fluxes and denitrification rates between sites was made, taking into account tidal immersion periods. Hence, N-removal by denitrification accounted for 156 mmol m -2 yr -1 in the inner station and 482 mmol m -2 yr -1 in the outer station. These rates represent respectively ca 3 and 9% of total DIN available in the estuarine water column at those 2 stations, respectively. N 2 O production was comparatively very low (0.3 to 0.6 mmol m -2 yr -1 ). The estimated nitrogen assimilation rates by microphytobenthos were 707 mmol m -2 yr -1 in the inner station and 333 mmol m -2 yr -1 in the outer station, indicating that a considerable amount of nitrogen was retained within benthic microalgae. The assimilation/denitrification ratio, with a mean value of 2, shows the relative importance of the denitrification role as a N-sink. Apart from denitrification, it is suggested that other processes must be involved in the removal of nitrogen from the estuary.

Book ChapterDOI
02 Apr 2000
TL;DR: The core part of the calculus is introduced, its basic syntactic properties are presented, and its use as a tool for programming language analysis is illustrated by a sound embedding of a secure multi-threaded imperative calculus of Volpano and Smith.
Abstract: We propose a new type discipline for the π-calculus in which secure information flow is guaranteed by static type checking. Secrecy levels are assigned to channels and are controlled by subtyping. A behavioural notion of types capturing causality of actions plays an essential role for ensuring safe information flow in diverse interactive behaviours, making the calculus powerful enough to embed known calculi for type-based security. The paper introduces the core part of the calculus, presents its basic syntactic properties, and illustrates its use as a tool for programming language analysis by a sound embedding of a secure multi-threaded imperative calculus of Volpano and Smith. The embedding leads to a practically meaningful extension of their original type discipline.