Showing papers by "Katholieke Universiteit Leuven published in 1998"

Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.

Abstract: As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor (HIF)-1alpha helps to restore oxygen homeostasis by inducing glycolysis, erythropoiesis and angiogenesis. Here we show that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (HIF-1alpha+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1alpha genes (HIF-1alpha-/-); however, a deficiency of HIF-1alpha does not affect apoptosis induced by cytokines. We find that hypoxia/hypoglycaemia-regulated genes involved in controlling the cell cycle are either HIF-1alpha-dependent (those encoding the proteins p53, p21, Bcl-2) or HIF-1alpha-independent (p27, GADD153), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients. Loss of HIF-1alpha reduces hypoxia-induced expression of vascular endothelial growth factor, prevents formation of large vessels in ES-derived tumours, and impairs vascular function, resulting in hypoxic microenvironments within the tumour mass. However, growth of HIF-1alpha tumours was not retarded but was accelerated, owing to decreased hypoxia-induced apoptosis and increased stress-induced proliferation. As hypoxic stress contributes to many (patho)biological disorders, this new role for HIF-1alpha in hypoxic control of cell growth and death may be of general pathophysiological importance.

The holographic Weyl anomaly

Abstract: We calculate the Weyl anomaly for conformal field theories that can be described via the adS/CFT correspondence. This entails regularizing the gravitational part of the corresponding supergravity action in a manner consistent with general covariance. Up to a constant, the anomaly only depends on the dimension d of the manifold on which the conformal field theory is defined. We present concrete expressions for the anomaly in the physically relevant cases d = 2,4 and 6. In d = 2 we find for the central charge c = 3l/2GN, in agreement with considerations based on the asymptotic symmetry algebra of adS3. In d = 4 the anomaly agrees precisely with that of the corresponding = 4 superconformal SU(N) gauge theory. The result in d = 6 provides new information for the (0, 2) theory, since its Weyl anomaly has not been computed previously. The anomaly in this case grows as N3, where N is the number of coincident M5 branes, and it vanishes for a Ricci-flat background.

Separate jasmonate-dependent and salicylate-dependent defense-response pathways in Arabidopsis are essential for resistance to distinct microbial pathogens

Abstract: The endogenous plant hormones salicylic acid (SA) and jasmonic acid (JA), whose levels increase on pathogen infection, activate separate sets of genes encoding antimicrobial proteins in Arabidopsis thaliana. The pathogen-inducible genes PR-1, PR-2, and PR-5 require SA signaling for activation, whereas the plant defensin gene PDF1.2, along with a PR-3 and PR-4 gene, are induced by pathogens via an SA-independent and JA-dependent pathway. An Arabidopsis mutant, coi1, that is affected in the JA-response pathway shows enhanced susceptibility to infection by the fungal pathogens Alternaria brassicicola and Botrytis cinerea but not to Peronospora parasitica, and vice versa for two Arabidopsis genotypes (npr1 and NahG) with a defect in their SA response. Resistance to P. parasitica was boosted by external application of the SA-mimicking compound 2,6-dichloroisonicotinic acid [Delaney, T., et al. (1994) Science 266, 1247–1250] but not by methyl jasmonate (MeJA), whereas treatment with MeJA but not 2,6-dichloroisonicotinic acid elevated resistance to Alternaria brassicicola. The protective effect of MeJA against A. brassicicola was the result of an endogenous defense response activated in planta and not a direct effect of MeJA on the pathogen, as no protection to A. brassicicola was observed in the coi1 mutant treated with MeJA. These data point to the existence of at least two separate hormone-dependent defense pathways in Arabidopsis that contribute to resistance against distinct microbial pathogens.

Concomitant activation of jasmonate and ethylene response pathways is required for induction of a plant defensin gene in Arabidopsis.

Abstract: Activation of the plant defensin gene PDF1.2 in Arabidopsis by pathogens has been shown previously to be blocked in the ethylene response mutant ein2-1 and the jasmonate response mutant coi1-1. In this work, we have further investigated the interactions between the ethylene and jasmonate signal pathways for the induction of this defense response. Inoculation of wild-type Arabidopsis plants with the fungus Alternaria brassicicola led to a marked increase in production of jasmonic acid, and this response was not blocked in the ein2-1 mutant. Likewise, A. brassicicola infection caused stimulated emission of ethylene both in wild-type plants and in coi1-1 mutants. However, treatment of either ein2-1 or coi1-1 mutants with methyl jasmonate or ethylene did not induce PDF1.2, as it did in wild-type plants. We conclude from these experiments that both the ethylene and jasmonate signaling pathways need to be triggered concomitantly, and not sequentially, to activate PDF1.2 upon pathogen infection. In support of this idea, we observed a marked synergy between ethylene and methyl jasmonate for the induction of PDF1.2 in plants grown under sterile conditions. In contrast to the clear interdependence of the ethylene and jasmonate pathways for pathogen-induced activation of PDF1.2, functional ethylene and jasmonate signaling pathways are not required for growth responses induced by jasmonate and ethylene, respectively.

Self-calibration and metric reconstruction in spite of varying and unknown internal camera parameters

Abstract: In this paper the feasibility of self-calibration in the presence of varying internal camera parameters is under investigation. A self-calibration method is presented which efficiently deals with all kinds of constraints on the internal camera parameters. Within this framework a practical method is proposed which can retrieve metric reconstruction from image sequences obtained with uncalibrated zooming/focusing cameras. The feasibility of the approach is illustrated on real and synthetic examples.

Analysis of 1.9 Mb of contiguous sequence from chromosome 4 of Arabidopsis thaliana

Abstract: The plant Arabidopsis thaliana (Arabidopsis) has become an important model species for the study of many aspects of plant biology. The relatively small size of the nuclear genome and the availability of extensive physical maps of the five chromosomes provide a feasible basis for initiating sequencing of the five chromosomes. The YAC (yeast artificial chromosome)-based physical map of chromosome 4 was used to construct a sequence-ready map of cosmid and BAC (bacterial artificial chromosome) clones covering a 1.9-megabase (Mb) contiguous region, and the sequence of this region is reported here. Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases (kb), and 54% of the predicted genes had significant similarity to known genes. Other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, the frequent occurrence of clustered gene families, and the sequence of several classes of genes not previously encountered in plants.

SOX10 mutations in patients with Waardenburg-Hirschsprung disease.

Abstract: Waardenburg syndrome (WS; deafness with pigmentary abnormalities) and Hirschsprung's disease (HSCR; aganglionic megacolon) are congenital disorders caused by defective function of the embryonic neural crest. WS and HSCR are associated in patients with Waardenburg-Shah syndrome (WS4), whose symptoms are reminiscent of the white coat-spotting and aganglionic megacolon displayed by the mouse mutants Dom (Dominant megacolon), piebald-lethal (sl) and lethal spotting (ls). The sl and ls phenotypes are caused by mutations in the genes encoding the Endothelin-B receptor (Ednrb) and Endothelin 3 (Edn3), respectively. The identification of Sox10 as the gene mutated in Dom mice (B.H. et al., manuscript submitted) prompted us to analyse the role of its human homologue SOX10 in neural crest defects. Here we show that patients from four families with WS4 have mutations in SOX10, whereas no mutation could be detected in patients with HSCR alone. These mutations are likely to result in haploinsufficiency of the SOX10 product. Our findings further define the locus heterogeneity of Waardenburg-Hirschsprung syndromes, and point to an essential role of SOX10 in the development of two neural crest-derived human cell lineages.

Oxidized LDL and Malondialdehyde-Modified LDL in Patients With Acute Coronary Syndromes and Stable Coronary Artery Disease

Abstract: Background—The association between oxidative modifications of LDL and coronary artery disease (CAD) is suspected but not established. Therefore, the association between plasma levels of oxidized LD...

Concepts and Principles of O-Linked Glycosylation

Abstract: The biosynthesis, structures, and functions of O-glycosylation, as a complex posttranslational event, is reviewed and compared for the various types of O-glycans. Mucin-type O-glycosylation is initiated by tissue-specific addition of a GalNAc-residue to a serine or a threonine of the fully folded protein. This event is dependent on the primary, secondary, and tertiary structure of the glycoprotein. Further elongation and termination by specific transferases is highly regulated. We also describe some of the physical and biological properties that O-glycosylation confers on the protein to which the sugars are attached. These include providing the basis for rigid conformations and for protein stability. Clustering of O-glycans in Ser/Thr(/Pro)-rich domains allows glycan determinants such as sialyl Lewis X to be presented as multivalent ligands, essential for functional recognition. An additional level of regulation, imposed by exon shuffling and alternative splicing of mRNA, results in the expression of prot...

Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization

Abstract: Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis.

Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research

Abstract: This study compares bone composition, density, and quality in bone samples derived from seven vertebrates that are commonly used in bone research: human, dog, pig, cow, sheep, chicken, and rat. Cortical femoral bone samples were analyzed for their content of ash, collagen, extractable proteins, and insulin-like growth factor-I. These parameters were also measured in bone powder fractions that were obtained after separation of bone particles according to their density. Large interspecies differences were observed in all analyses. Of all species included in the biochemical analyses, rat bone was most different, whereas canine bone best resembled human bone. In addition, bone density and mechanical testing analyses were performed on cylindrical trabecular bone cores. Both analyses demonstrated large interspecies variations. The lowest bone density and fracture stress values were found in the human samples; porcine and canine bone best resembled these samples. The relative contribution of bone density to bone mechanical competence was largely species-dependent. Together, the data reported here suggest that interspecies differences are likely to be found in other clinical and experimental bone parameters and should therefore be considered when choosing an appropriate animal model for bone research.

Plant Lectins: A Composite of Several Distinct Families of Structurally and Evolutionary Related Proteins with Diverse Biological Roles

Abstract: Many plants contain carbohydrate-binding proteins that are commonly designated as lectins, agglutinins, or hemagglutinins. Due to the obvious differences in molecular structure, biochemical properties, and carbohydrate-binding specificity, plant lectins are usually considered a complex and heterogeneous group of proteins. Recent advances in the structural analysis of lectins and molecular cloning of lectin genes enable subdividision of plant lectins in a limited number of subgroups of structurally and evolutionary related proteins. Four major lectin families, namely, the legume lectins, the chitin-binding lectins composed of hevein domains, the type 2 ribosome-inactivating proteins, and the monocot mannose-binding lectins comprise the majority of all currently known plant lectins. In addition to these four large families the jacalin-related lectins, the amaranthin family, and the Cucurbitaceae phloem lectins are now recognized as separate subgroups. Each of the above-mentioned lectin families is discussed...

Strong Enhancement of Nonlinear Optical Properties Through Supramolecular Chirality

Abstract: A new approach to second-order nonlinear optical (NLO) materials is reported, in which chirality and supramolecular organization play key roles. Langmuir-Blodgett films of a chiral helicene are composed of supramolecular arrays of the molecules. The chiral supramolecular organization makes the second-order NLO susceptibility about 30 times larger for the nonracemic material than for the racemic material with the same chemical structure. The susceptibility of the nonracemic films is a respectable 50 picometers per volt, even though the helicene structure lacks features commonly associated with high nonlinearity. Susceptibility components that are allowed only by chirality dominate the second-order NLO response.

Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice.

Abstract: The development of colorectal cancer, one of the most frequent cancers, is influenced by prostaglandins and fatty acids. Decreased prostaglandin production, seen in mice with mutations in the cyclooxygenase 2 gene or in animals and humans treated with cyclooxygenase inhibitors, prevents or attenuates colon cancer development. There is also a strong correlation between the intake of fatty acids from animal origin and colon cancer. Therefore, the peroxisome proliferator-activated receptor gamma (PPARgamma), a downstream transcriptional mediator for prostaglandins and fatty acids which is highly expressed in the colon may be involved in this process. Activation of PPARgamma by two different synthetic agonists increased the frequency and size of colon tumors in C57BL/6J-APCMin/+ mice, an animal model susceptible to intestinal neoplasia. Tumor frequency was only increased in the colon, and did not change in the small intestine, coinciding with the colon-restricted expression of PPARgamma. Treatment with PPARgamma agonists increased beta-catenin levels both in the colon of C57BL/61-APCMin/+ mice and in HT-29 colon carcinoma cells. Genetic abnormalities in the Wnt/wingless/APC pathway, which enhance the transcriptional activity of the beta-catenin-T-cell factor/lymphoid enhancer factor 1 transcription complex, often underly the development of colon tumors. Our data indicate that PPARgamma activation modifies the development of colon tumors in C57BL/61-APCMin/+ mice.

New insights in the relation between electron trap generation and the statistical properties of oxide breakdown

Abstract: In this paper it is demonstrated in a wide stress field range that breakdown in thin oxide layers occurs as soon as a critical density of neutral electron traps in the oxide is reached. It is proven that this corresponds to a critical hole fluence, since a unique relationship between electron trap generation and hole fluence is found independent of stress field and oxide thickness. In this way literature models relating breakdown to hole fluence or to trap generation are linked. A new model for intrinsic breakdown, based on a percolation concept, is proposed. It is shown that this model can explain the experimentally observed statistical features of the breakdown distribution, such as the increasing spread of the Q/sub BD/-distribution for ultrathin oxides. An important consequence of this large spread is the strong area dependence of the Q/sub BD/ for ultrathin oxides.

Hydrothermal Modifications of Granular Starch, with Retention of the Granular Structure: A Review

Abstract: Annealing and heat−moisture treatment are two hydrothermal treatments that modify the physicochemical properties of starch, without destroying granular structure They involve incubation of starch granules in excess water/intermediate water content (annealing) or at low moisture levels (heat−moisture treatment) during a certain period of time, at a temperature above the glass transition temperaturr but below the gelatinization temperature The impact of hydrothermal treatments on starch physicochemical properties is extensively discussed Such physicochemical properties include granule morphology and crystallinity, double-helix content, amount and appearance of amylose−lipid complexes, gelatinization and pasting, swelling power and solubility, gel properties, and susceptibilities to acid and enzymic hydrolysis Finally, the major differences between the effects of annealing and heat−moisture treatment are pointed out and an overview is given of possible explanations for the observed effects of hydrotherma

Team Sports and the Theory of Deliberate Practice

Abstract: Two studies tested the theory of deliberate practice (Ericsson, Krampe, & Tesch-Romer, 1993) and contrasted results with the sport commitment model (Scanlan, Carpenter, Schmidt, Simons, & Keeler, 1993a, 1993b). In Part I, international, national, and provincial soccer and field hockey players recalled the amount of time they spent in individual and team practice, sport-related activities, and everyday activities at the start of their career and every 3 years since. In Part II, these activities were rated in terms of their relevance for improving performance, effort and concentration required, and enjoyment. A monotonic relationship between accumulated individual plus team practice and skill level was found. In contrast with Ericsson et al.’s (1993) findings for musicians, relevant activities were also enjoyable, while concentration became a separate dimension from effort. The viability of a generalized theory of expertise is discussed.

Low-IF topologies for high-performance analog front ends of fully integrated receivers

Abstract: When it comes to integratability, the zero-intermediate frequency (IF) receiver is an alternative for the heterodyne or IF receiver. In recent years, the zero-IF receiver has been introduced in several applications, but its performance cannot be compared to that of the IF receiver yet. This lower performance is closely related to its baseband operation, resulting in filter saturation and distortion, both caused by DC-offsets and self-mixing at the inputs of the mixers. The low-IF receiver has a topology which is closely related to the zero-IF receiver, but it does not operate in the baseband, only near the baseband. The consequences are that, as for the zero-IF receiver, the implementation of a low-IF receiver can be done with a high degree of integration, however, its performance can be better. In this paper, the fundamental principles of the low-IF receiver topology are introduced. Different low-IF receiver topologies are synthesized and fully analyzed in this paper. This is done by applying the complex signal technique-a technique used in digital applications to the study of analog receiver front ends.

Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth.

Abstract: Pronounced adrenarche with precocious pubarche (PP) in girls has been associated with hyperinsulinism and subsequent functional ovarian hyperandrogenism (FOH). Recently, pronounced adrenarche and insulin resistance have each been related to low birth weight. We have now tested the hypothesis that the frequent concurrence of PP with pronounced adrenarche, FOH, and hyperinsulinemia in girls may be secondary to separate relationships between these conditions and low birth weight. A total of 185 girls (aged 5-18 yr) without endocrinopathy or with PP and pronounced adrenarche with or without FOH were studied; mean serum insulin (MSI) concentrations were determined after a standardized oral glucose tolerance test. Birth weight SD scores [mean (SEM)] of control girls (0.38+/-0.08; n = 83) were higher (P < 0.0001) than those of PP girls (-0.81+/-0.13; n = 102). Among postmenarcheal PP girls, birth weight SD scores of girls without FOH (-0.25+/-0.19; n = 25) were higher (P < 0.0001) than those in girls with FOH (-1.51+/-0.28; n = 23). In pubertal girls (n = 145), MSI levels correlated negatively with birth weight SD scores (r = -0.48; P < 0.05), independently of PP. MSI levels in girls with birth weight below 1 SD (93+/-9 mU/L; n = 33) were higher (P < 0.0001) than those in girls with birth weight between -1 and +1 SD (52+/-2 mU/L; n = 94), whereas glycemia profiles were comparable. Integration of the aforementioned data suggests that there may be a sequence in the associations between reduced fetal growth and components of the postnatal endocrine system; minor fetal growth reduction appears to be associated with amplified adrenarche, whereas more pronounced prenatal growth restriction seem to precede FOH and hyperinsulinemia during adolescence. In conclusion, these findings corroborate the hypothesis that the frequent concurrence of PP (with pronounced adrenarche), FOH, and hyperinsulinemia in girls may result from a common early origin (low birth weight serving as a marker), rather than from a direct interrelationship later in life.

Top-Down Induction of Clustering Trees

Abstract: An approach to clustering is presented that adapts the basic top-down induction of decision trees method towards clustering. To this aim, it employs the principles of instance based learning. The resulting methodology is implemented in the TIC (Top down Induction of Clustering trees) system for first order clustering. The TIC system employs the first order logical decision tree representation of the inductive logic programming system Tilde. Various experiments with TIC are presented, in both propositional and relational domains.