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Showing papers by "Ghent University published in 2001"


Journal ArticleDOI
TL;DR: List of participants (GOLD Scientific Committee): Nicholas Anthonisen, Winnipeg, Canada, William C. Bailey, Birmingham, US, Tim Clark, London, UK, Leonardo Fabbri, Modena, Italy, Yoshinosuke Fukuchi, Tokyo, Japan; Lawrence Grouse, Seattle, US; James C. Hogg, Vancouver, Canada; Dirkje S. Postma, Groningen, the Netherlands.

5,740 citations


Journal ArticleDOI
TL;DR: In this paper, the authors found that risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known, and the women were randomly assigned to receive treatment with either oral risingronate (2.5 or 5.0 mg) or placebo for three years.
Abstract: Background Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known. Methods We studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [–4] or lower than –3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than –4 or lower than –3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture. Results Overall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned t...

1,719 citations


Journal ArticleDOI
TL;DR: It is reported that expression of wild-type but not of mutated SIP1 downregulates mammalian E-cadherin transcription via binding to both conserved E2 boxes of the minimal E- cadheringin promoter.

1,369 citations


Journal ArticleDOI
TL;DR: Characterization of lateral root development in the shoot meristemless1 mutant demonstrates that root basipetal and leaf acropetal auxin transport activities are required during the initiation and emergence phases, respectively, of lateralRoot development.
Abstract: Lateral root development in Arabidopsis provides a model for the study of hormonal signals that regulate postembryonic organogenesis in higher plants. Lateral roots originate from pairs of pericycle cells, in several cell files positioned opposite the xylem pole, that initiate a series of asymmetric, transverse divisions. The auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) arrests lateral root development by blocking the first transverse division(s). We investigated the basis of NPA action by using a cell-specific reporter to demonstrate that xylem pole pericycle cells retain their identity in the presence of the auxin transport inhibitor. However, NPA causes indoleacetic acid (IAA) to accumulate in the root apex while reducing levels in basal tissues critical for lateral root initiation. This pattern of IAA redistribution is consistent with NPA blocking basipetal IAA movement from the root tip. Characterization of lateral root development in the shoot meristemless1 mutant demonstrates that root basipetal and leaf acropetal auxin transport activities are required during the initiation and emergence phases, respectively, of lateral root development.

995 citations



Journal ArticleDOI
TL;DR: The results suggest a novel mechanism by which metalloproteinases can influence invasion, as indicated by induction of invasion into collagen type I and inhibition of E-cadherin-dependent cell aggregation.
Abstract: The function of many transmembrane molecules can be altered by cleavage and subsequent release of their ectodomains. We have investigated ectodomain cleavage of the cell-cell adhesion and signal-transducing molecule E-cadherin. The E-cadherin ectodomain is constitutively shed from the surface of MCF-7 and MDCKts.srcC12 cells in culture. Release of the 80 kDa soluble E-cadherin fragment is stimulated by phorbol-12-myristate-13-acetate and is inhibited by overexpression of the tissue inhibitor of metalloproteinases-2. The metalloproteinases matrilysin and stromelysin-1 both cleave E-cadherin at the cell surface and release sE-CAD into the medium. The soluble E-cadherin fragment thus released inhibits E-cadherin functions in a paracrine way, as indicated by induction of invasion into collagen type I and inhibition of E-cadherin-dependent cell aggregation. Our results, therefore, suggest a novel mechanism by which metalloproteinases can influence invasion.

722 citations


Book
18 Oct 2001
TL;DR: A consequence of aerobic life is the formation of reactive forms of oxygen such as Superoxide radicals (O2•), hydrogen peroxide (H2O2), and hydroxyl radicals (OH•) as discussed by the authors.
Abstract: A consequence of aerobic life is the formation of reactive forms of oxygen such as Superoxide radicals (O2•), hydrogen peroxide (H2O2), and hydroxyl radicals (OH•). In particular, hydroxyl radicals are one of the most reactive species known to chemistry, being able to react with DNA, proteins, lipids, and almost any other constituent of living cells (Halliwell, 1984). Its primary route of formation is thought to be an iron-catalyzed reaction of Superoxide radicals with hydrogen peroxide as follows

689 citations


Journal ArticleDOI
TL;DR: It is proved that many fuzzy relations used for the comparison of fuzzy quantities satisfy some conditions stronger than acyclicity, so a widely applicable formulation to derive a total ranking order from a fuzzy relation is given.

674 citations


Journal ArticleDOI
TL;DR: In this paper, a review of the involvement of active oxygen species (AOS) in stress signal transduction in plants, guided by a summary of work performed in our laboratory on plants that are deficient in catalase activity, is presented.

671 citations


Journal ArticleDOI
TL;DR: It is concluded that KRP2 exerts a plant growth inhibitory activity by reducing cell proliferation in leaves, but, in contrast to its mammalian counterparts, it may not control the timing of cell cycle exit and differentiation.
Abstract: Cyclin-dependent kinase inhibitors, such as the mammalian p27Kip1 protein, regulate correct cell cycle progression and the integration of developmental signals with the core cell cycle machinery. These inhibitors have been described in plants, but their function remains unresolved. We have isolated seven genes from Arabidopsis that encode proteins with distant sequence homology with p27Kip1, designated Kip-related proteins (KRPs). The KRPs were characterized by their domain organization and transcript profiles. With the exception of KRP5, all presented the same cyclin-dependent kinase binding specificity. When overproduced, KRP2 dramatically inhibited cell cycle progression in leaf primordia cells without affecting the temporal pattern of cell division and differentiation. Mature transgenic leaves were serrated and consisted of enlarged cells. Although the ploidy levels in young leaves were unaffected, endoreduplication was suppressed in older leaves. We conclude that KRP2 exerts a plant growth inhibitory activity by reducing cell proliferation in leaves, but, in contrast to its mammalian counterparts, it may not control the timing of cell cycle exit and differentiation.

652 citations


Journal ArticleDOI
TL;DR: This review principally focuses on ash from the wood industry and power plants and considers its physical, chemical and mineralogical characteristics, its effect on soil properties, on the availability of nutrient elements and on the growth and chemical composition of crops and trees, as well as its impact on the environment.

Journal ArticleDOI
TL;DR: (GTG)(5)-PCR was found to be a promising genotypic tool for rapid and reliable speciation and typing of lactobacilli and other lactic acid bacteria important in food-fermentation industries.
Abstract: PCR amplification of repetitive bacterial DNA elements fingerprinting using the (GTG)5 primer ((GTG)5-PCR) was proven to be useful for differentiation of a wide range of lactobacilli (i.e. 26 different (sub)species) at the species, subspecies and potentially up to the strain level. Using this rapid and reproducible genotypic technique, new Lactobacillus isolates recovered from different types of fermented dry sausage could be reliable identified at the (sub)species level. In conclusion, (GTG)5-PCR was found to be a promising genotypic tool for rapid and reliable speciation and typing of lactobacilli and other lactic acid bacteria important in food-fermentation industries.

Journal ArticleDOI
TL;DR: A proteome analysis of the model plant Arabidopsis revealed new proteins associated with the different phases of seed germination and priming and highlighted the power of proteomics to unravel specific features of complex developmental processes such as germination.
Abstract: To better understand seed germination, a complex developmental process, we developed a proteome analysis of the model plant Arabidopsis for which complete genome sequence is now available. Among about 1,300 total seed proteins resolved in two-dimensional gels, changes in the abundance (up- and down-regulation) of 74 proteins were observed during germination sensu stricto (i.e. prior to radicle emergence) and the radicle protrusion step. This approach was also used to analyze protein changes occurring during industrial seed pretreatments such as priming that accelerate seed germination and improve seedling uniformity. Several proteins were identified by matrix-assisted laser-desorption ionization time of flight mass spectrometry. Some of them had previously been shown to play a role during germination and/or priming in several plant species, a finding that underlines the usefulness of using Arabidopsis as a model system for molecular analysis of seed quality. Furthermore, the present study, carried out at the protein level, validates previous results obtained at the level of gene expression (e.g. from quantitation of differentially expressed mRNAs or analyses of promoter/reporter constructs). Finally, this approach revealed new proteins associated with the different phases of seed germination and priming. Some of them are involved either in the imbibition process of the seeds (such as an actin isoform or a WD-40 repeat protein) or in the seed dehydration process (e.g. cytosolic glyceraldehyde-3-phosphate dehydrogenase). These facts highlight the power of proteomics to unravel specific features of complex developmental processes such as germination and to detect protein markers that can be used to characterize seed vigor of commercial seed lots and to develop and monitor priming treatments.

Journal ArticleDOI
TL;DR: The discovery of a fourth rhizobial branch involving bacteria of the Methylobacterium genus is reported, which is closely related to Bradyrhizobium NodA, suggesting that this gene was acquired by horizontal gene transfer.
Abstract: Rhizobia described so far belong to three distinct phylogenetic branches within the alpha-2 subclass of Proteobacteria. Here we report the discovery of a fourth rhizobial branch involving bacteria of the Methylobacterium genus. Rhizobia isolated from Crotalaria legumes were assigned to a new species, "Methylobacterium nodulans," within the Methylobacterium genus on the basis of 16S ribosomal DNA analyses. We demonstrated that these rhizobia facultatively grow on methanol, which is a characteristic of Methylobacterium spp. but a unique feature among rhizobia. Genes encoding two key enzymes of methylotrophy and nodulation, the mxaF gene, encoding the alpha subunit of the methanol dehydrogenase, and the nodA gene, encoding an acyltransferase involved in Nod factor biosynthesis, were sequenced for the type strain, ORS2060. Plant tests and nodA amplification assays showed that "M. nodulans" is the only nodulating Methylobacterium sp. identified so far. Phylogenetic sequence analysis showed that "M. nodulans" NodA is closely related to Bradyrhizobium NodA, suggesting that this gene was acquired by horizontal gene transfer.

Journal ArticleDOI
TL;DR: Populus is presented as a model system for the study of wood formation and high-resolution analysis of auxin distribution across cambial region tissues suggests that auxin provides positional information for the exit of cells from the meristem and probably also for the duration of cell expansion.
Abstract: Populus is presented as a model system for the study of wood formation (xylogenesis). The formation of wood (secondary xylem) is an ordered developmental process involving cell division, cell expansion, secondary wall deposition, lignification and programmed cell death. Because wood is formed in a variable environment and subject to developmental control, xylem cells are produced that differ in size, shape, cell wall structure, texture and composition. Hormones mediate some of the variability observed and control the process of xylogenesis. High-resolution analysis of auxin distribution across cambial region tissues, combined with the analysis of transgenic plants with modified auxin distribution, suggests that auxin provides positional information for the exit of cells from the meristem and probably also for the duration of cell expansion. Poplar sequencing projects have provided access to genes involved in cell wall formation. Genes involved in the biosynthesis of the carbohydrate skeleton of the cell wall are briefly reviewed. Most progress has been made in characterizing pectin methyl esterases that modify pectins in the cambial region. Specific expression patterns have also been found for expansins, xyloglucan endotransglycosylases and cellulose synthases, pointing to their role in wood cell wall formation and modification. Finally, by studying transgenic plants modified in various steps of the monolignol biosynthetic pathway and by localizing the expression of various enzymes, new insight into the lignin biosynthesis in planta has been gained.

Journal ArticleDOI
TL;DR: VEGF is identified as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes and may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.
Abstract: Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.

Journal ArticleDOI
TL;DR: Since no artificial feed formulation is yet available to completely substitute for Artemia, feeding live prey to young fish larvae still remains essential in commercial hatchery operations.

Journal ArticleDOI
TL;DR: Mutations were found at early noninvasive stages, associating E-cadherin mutations with loss of cell growth control and defining CDH1 as the tumor suppressor for the lobular breast cancer subtype.
Abstract: E-cadherin is a cell–cell adhesion protein fulfilling a prominent role in epithelial differentiation. Data from model systems suggest that E-cadherin is a potent invasion/tumor suppressor of breast cancer. Consistent with this role in breast cancer progression, partial or complete loss of E-cadherin expression has been found to correlate with poor prognosis in breast cancer patients. The E-cadherin gene (CDH1) is located on human chromosome 16q22.1, a region frequently affected with loss of heterozygosity in sporadic breast cancer. Invasive lobular breast carcinomas, which are typically completely E-cadherin-negative, often show inactivating mutations in combination with loss of heterozygosity of the wild-type CDH1 allele. Mutations were found at early noninvasive stages, thus associating E-cadherin mutations with loss of cell growth control and defining CDH1 as the tumor suppressor for the lobular breast cancer subtype. Ductal breast cancers in general show heterogeneous loss of E-cadherin expression, associated with epigenetic transcriptional downregulation. It is proposed that the microenvironment at the invasive front is transiently downregulating E-cadherin transcription. This can be associated with induction of nonepithelial cadherins.

Journal ArticleDOI
TL;DR: At the beginning of this review it is essential to clarify the terminology that will be used to refer to the members of the Burkholderia cepacia complex and their relatives.
Abstract: At the beginning of this review it is essential to clarify the terminology that will be used to refer to the members of the Burkholderia cepacia complex and their relatives. The name B. cepacia will relate only to B. cepacia genomovar I. Strains resembling B. cepacia may belong to the B. cepacia

Journal ArticleDOI
TL;DR: An international round robin test on the analysis of carbonaceous aerosols on quartz fiber filters sampled at an urban site was organized by the Vienna University of Technology as discussed by the authors, where 17 laboratories participated using nine different thermal and optical methods.

Journal ArticleDOI
TL;DR: The best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods.
Abstract: Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5 per thousand and the interquartile range was between 3 and 12 per thousand. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods.

Journal ArticleDOI
G. Lindström1, M. Ahmed2, Sebastiano Albergo, Phillip Allport3, D.F. Anderson4, Ladislav Andricek5, M. Angarano6, Vincenzo Augelli, N. Bacchetta, P. Bartalini6, Richard Bates7, U. Biggeri, G. M. Bilei6, Dario Bisello, D. Boemi, E. Borchi, T. Botila, T. J. Brodbeck8, Mara Bruzzi, T. Budzyński, P. Burger, Francesca Campabadal9, Gianluigi Casse3, E. Catacchini, A. Chilingarov8, Paolo Ciampolini6, Vladimir Cindro10, M. J. Costa9, Donato Creanza, Paul Clauws11, C. Da Via2, Gavin Davies12, W. De Boer13, Roberto Dell'Orso, M. De Palma, B. Dezillie14, V. K. Eremin, O. Evrard, Giorgio Fallica15, Georgios Fanourakis, H. Feick16, Ettore Focardi, Luis Fonseca9, E. Fretwurst1, J. Fuster9, K. Gabathuler, Maurice Glaser17, Piotr Grabiec, E. Grigoriev13, Geoffrey Hall18, M. Hanlon3, F. Hauler13, S. Heising13, A. Holmes-Siedle2, Roland Horisberger, G. Hughes8, Mika Huhtinen17, I. Ilyashenko, Andrew Ivanov, B.K. Jones8, L. Jungermann13, A. Kaminsky, Z. Kohout19, Gregor Kramberger10, M Kuhnke1, Simon Kwan4, F. Lemeilleur17, Claude Leroy20, M. Letheren17, Z. Li14, Teresa Ligonzo, Vladimír Linhart19, P.G. Litovchenko21, Demetrios Loukas, Manuel Lozano9, Z. Luczynski, Gerhard Lutz5, B. C. MacEvoy18, S. Manolopoulos7, A. Markou, C Martinez9, Alberto Messineo, M. Mikuž10, Michael Moll17, E. Nossarzewska, G. Ottaviani, Val O'Shea7, G. Parrini, Daniele Passeri6, D. Petre, A. Pickford7, Ioana Pintilie, Lucian Pintilie, Stanislav Pospisil19, Renato Potenza, C. Raine7, Joan Marc Rafi9, P. N. Ratoff8, Robert Richter5, Petra Riedler17, Shaun Roe17, P. Roy20, Arie Ruzin22, A.I. Ryazanov23, A. Santocchia18, Luigi Schiavulli, P. Sicho24, I. Siotis, T. J. Sloan8, W. Slysz, Kristine M. Smith7, M. Solanky2, B. Sopko19, K. Stolze, B. Sundby Avset25, B. G. Svensson26, C. Tivarus, Guido Tonelli, Alessia Tricomi, Spyros Tzamarias, Giusy Valvo15, A. Vasilescu, A. Vayaki, E. M. Verbitskaya, Piero Giorgio Verdini, Vaclav Vrba24, Stephen Watts2, Eicke R. Weber16, M. Wegrzecki, I. Węgrzecka, P. Weilhammer17, R. Wheadon, C.D. Wilburn27, I. Wilhelm28, R. Wunstorf29, J. Wüstenfeld29, J. Wyss, K. Zankel17, P. Zabierowski, D. Žontar10 
TL;DR: In this paper, a defect engineering technique was employed resulting in the development of Oxygen enriched FZ silicon (DOFZ), ensuring the necessary O-enrichment of about 2×1017 O/cm3 in the normal detector processing.
Abstract: The RD48 (ROSE) collaboration has succeeded to develop radiation hard silicon detectors, capable to withstand the harsh hadron fluences in the tracking areas of LHC experiments. In order to reach this objective, a defect engineering technique was employed resulting in the development of Oxygen enriched FZ silicon (DOFZ), ensuring the necessary O-enrichment of about 2×1017 O/cm3 in the normal detector processing. Systematic investigations have been carried out on various standard and oxygenated silicon diodes with neutron, proton and pion irradiation up to a fluence of 5×1014 cm−2 (1 MeV neutron equivalent). Major focus is on the changes of the effective doping concentration (depletion voltage). Other aspects (reverse current, charge collection) are covered too and the appreciable benefits obtained with DOFZ silicon in radiation tolerance for charged hadrons are outlined. The results are reliably described by the “Hamburg model”: its application to LHC experimental conditions is shown, demonstrating the superiority of the defect engineered silicon. Microscopic aspects of damage effects are also discussed, including differences due to charged and neutral hadron irradiation.

Journal ArticleDOI
TL;DR: It is concluded that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to theIRSp53 SH3 domain.

Journal ArticleDOI
TL;DR: Strains exhibiting virulence traits were not necessarily positive for all traits; thus, the incidence of virulence factors may be considered to be strain specific.
Abstract: The incidence of virulence factors among 48 Enterococcus faecium and 47 Enterococcus faecalis strains from foods and their antibiotic susceptibility were investigated. No strain was resistant to all antibiotics, and for some strains, multiple resistances were observed. Of E. faecium strains, 10.4% were positive for one or more virulence determinants, compared to 78.7% of E. faecalis strains. Strains exhibiting virulence traits were not necessarily positive for all traits; thus, the incidence of virulence factors may be considered to be strain specific.

Posted Content
TL;DR: In this article, the authors present a complete set of results describing the effects of monetary policy in 10 countries of the Euro area for the pre-EMU period and show that an unexpected rise in the short-term interest rate leads to a decrease in GDP, with investment and exports falling more than consumption.
Abstract: This paper presents a complete set of results describing the effects of monetary policy in 10 countries of the Euro area for the pre-EMU period. For each country, we impose one of three identification schemes depending on its monetary integration with Germany, the nominal anchor of the ERM. The first identification scheme applies to Germany, the second to countries of the core EMS (Austria, Belgium and the Netherlands) and the third to all the other countries. An unexpected rise in the short-term interest rate leads to a decrease in GDP, (with investment and exports falling more than consumption) and a gradual decrease in prices for all countries. We also show that, given the width of the error bands around the estimate, we cannot reject that the effects of monetary policy on GDP and on prices are broadly similar in the individual countries of the Euro area.

Journal ArticleDOI
TL;DR: The aim of this work is to study the functional equations of Frank and Alsina for two classes of commutative, associative and increasing binary operators, one of which is the class of uninorms introduced by Yager and Rybalov and the other is theclass of nullnorms arising from the study of the Frank equation for uninormS.

Journal ArticleDOI
TL;DR: The ability of truncated Bid (tBid) to induce the release of a DNAse activity from mitochondria during apoptosis was confirmed in the liver from mice injected with agonistic anti-Fas antibody and is completely prevented in Bcl-2 transgenic mice.
Abstract: A hallmark of apoptosis is the fragmentation of nuclear DNA. Although this activity involves the caspase-3-dependent DNAse CAD (caspase-activated DNAse), evidence exists that DNA fragmentation can occur independently of caspase activity. Here we report on the ability of truncated Bid (tBid) to induce the release of a DNAse activity from mitochondria. This DNAse activity was identified by mass spectrometry as endonuclease G, an abundant 30 kDa protein released from mitochondria under apoptotic conditions. No tBid-induced endonuclease G release could be observed in mitochondria from Bcl-2-transgenic mice. The in vivo occurrence of endonuclease G release from mitochondria during apoptosis was confirmed in the liver from mice injected with agonistic anti-Fas antibody and is completely prevented in Bcl-2 transgenic mice. These data indicate that endonuclease G may be involved in CAD-independent DNA fragmentation during cell death pathways in which truncated Bid is generated.

Journal ArticleDOI
TL;DR: It is shown by direct transport assays that arsenite uptake is mediated by Fps1p, and the first report describing a eukaryotic uptake mechanism for arsenite and antimonite and its involvement in metalloid tolerance is described.
Abstract: Laboratorium voor Moleculaire Celbiologie, KatholiekeUniversiteit Leuven, Kasteelpark Arenberg 31, B-3001Leuven-Heverlee, Flanders, Belgium.SummaryThe Saccharomyces cerevisiae FPS1 gene encodes aglycerol channel protein involved in osmoregulation.We present evidence that Fps1p mediates influx of thetrivalent metalloids arsenite and antimonite in yeast.Deletion of FPS1 improves tolerance to arsenite andpotassium antimonyl tartrate. Under high osmolarityconditions, when the Fps1p channel is closed, wild-type cells show the same degree of As(III) and Sb(III)tolerance as the fps1Dmutant. Additional deletion ofFPS1 in mutants defective in arsenite and antimonitedetoxification partially suppresses their hypersensi-tivity to metalloid salts. Cells expressing a constitu-tively open form of the Fps1p channel are highlysensitive to both arsenite and antimonite. We alsoshow by direct transport assays that arsenite uptakeis mediated by Fps1p. Yeast cells appear to controlthe Fps1p-mediated pathway of metalloid uptake, asexpression of the FPS1 gene is repressed upon As(III)and Sb(III) addition. To our knowledge, this is the firstreport describing a eukaryotic uptake mechanism forarsenite and antimonite and its involvement inmetalloid tolerance.IntroductionArsenic and antimony are toxic metalloids with a longhistory of usage as therapeutic agents. Paul Ehrlichshowedatthebeginningofthetwentiethcenturythatsomeinfectious diseases such as syphilis and trypanosomiasiscould be treated successfully with organic derivatives ofarsenic (Xu et al., 1998). In addition, potassium arsenitewas used for controlling the level of leucocytes in patientssuffering from chronic myelocytic leukaemia until the1930s (Forkner and McNair-Scott, 1931). Although thesedrugs have been replaced with more effective and lesstoxic agents, the organic arsenical melarsoprol is still inuse for the treatment of sleeping sickness. Likewise, allforms of leishmaniasis are treated with drugs containingthe related metalloid antimony (Borst and Ouellette,1995).Arsenic trioxide has been shown recently to be a highlyeffective and relatively safe drug in treating patients withacute promyelocytic leukaemia who are resistant toconventional chemotherapy (Shen et al., 1997; Soignetetal.,1998).Invitrostudieshaverevealedthatantimonialsand melarsoprol inhibit growth and induce apoptosis ofleukaemia cells in a similar way to arsenic trioxide andcould therefore be used in antileukaemic therapy (Mu¨lleret al., 1998; Wang et al., 1998; Rousselot et al., 1999).There is promising evidence that arsenic trioxide causesapoptosis of both haematologic and solid tumour celllines in vitro and that it might also be effective in vivo(Ko¨nig et al., 1997; Yang et al., 1999; Zhang et al., 1999).However, the development of clinical resistance in somepatients treated with arsenic trioxide suggests thepresence of resistance mechanisms (Soignet et al.,1998). Hence, it is of interest to elucidate the molecularmechanisms involved in resistance to both arsenic andantimony in eukaryotes.Although tolerance to arsenic and antimony salts iswelldefined inbacteria, therehasbeenlittle informationonsuch mechanisms in eukaryotic cells (Silver, 1998; Rosen,1999a, b). Several genes of the eukaryotic modelorganism Saccharomyces cerevisiae (baker’s yeast)have been shown recently to affect metalloid tolerance,which hascontributed toa rapid progress in understandingthis phenomenon.Arsenite [As(III)] and arsenate [As(V)] tolerance in yeastis mediated by a cluster of three genes: ACR1 (ARR1,YAP8), ACR2 (ARR2) and ACR3 (ARR3) (Bobrowiczet al., 1997). The ACR1 gene encodes a transcriptionfactor belonging to the fungus-specific Yap family of bZIPproteins (Fernandes et al., 1997). Acr1p appears to beinvolved in controlling the induction of ACR2 and ACR3

Journal ArticleDOI
TL;DR: In this paper, a modeling approach for photonic crystal structures and vertical-cavity surface-emitting lasers (VCSELs) is presented based on vectorial eigenmode expansion combined with perfectly matched layer (PML) boundary conditions.
Abstract: We present a modelling approach for photonic crystal structures and vertical-cavity surface-emitting lasers (VCSELs). This method is based on vectorial eigenmode expansion combined with perfectly matched layer (PML) boundary conditions. Compared to other methods, a relatively small computational effort is required, while at the same time accurate results are obtained, even in the presence of strong scattering and diffraction losses.

Journal ArticleDOI
TL;DR: The gene that encoded the cytosolic class II smHSP in Arabidopsis thaliana was characterized and its expression was induced by heat and osmotic stress, as well as during seed development, suggesting stress-induced post-transcriptional regulation of At-HSP17.6A expression.
Abstract: Owing to their sessile lifestyle, it is crucial for plants to acquire stress tolerance. The function of heat-shock proteins, including small heat-shock proteins (smHSPs), in stress tolerance is not fully explored. To gain further knowledge about the smHSPs, the gene that encoded the cytosolic class II smHSP in Arabidopsis thaliana (At-HSP17.6A) was characterized. The At-HSP17.6A expression was induced by heat and osmotic stress, as well as during seed development. Accumulation of At-HSP17.6A proteins could be detected with heat and at a late stage of seed development, but not with osmotic stress, suggesting stress-induced post-transcriptional regulation of At-HSP17.6A expression. Overproduction of At-HSP17.6A could increase salt and drought tolerance in Arabidopsis. The chaperone activity of At-HSP17.6A was demonstrated in vitro.