Showing papers by "Hungarian Academy of Sciences published in 2003"

Role of Endogenous Cannabinoids in Synaptic Signaling

Abstract: Research of cannabinoid actions was boosted in the 1990s by remarkable discoveries including identification of endogenous compounds with cannabimimetic activity (endocannabinoids) and the cloning of their molecular targets, the CB1 and CB2 receptors. Although the existence of an endogenous cannabinoid signaling system has been established for a decade, its physiological roles have just begun to unfold. In addition, the behavioral effects of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, the major active compound of hashish and marijuana, await explanation at the cellular and network levels. Recent physiological, pharmacological, and high-resolution anatomical studies provided evidence that the major physiological effect of cannabinoids is the regulation of neurotransmitter release via activation of presynaptic CB1 receptors located on distinct types of axon terminals throughout the brain. Subsequent discoveries shed light on the functional consequences of this localization by demonstrating the involvement of endocannabinoids in retrograde signaling at GABAergic and glutamatergic synapses. In this review, we aim to synthesize recent progress in our understanding of the physiological roles of endocannabinoids in the brain. First, the synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. The fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release. Finally, the possible functions of endocannabinoids as retrograde synaptic signal molecules are discussed in relation to synaptic plasticity and network activity patterns.

Microstructural evolution during film growth

Abstract: Atomic-scale control and manipulation of the microstructure of polycrystalline thin films during kinetically limited low-temperature deposition, crucial for a broad range of industrial applications, has been a leading goal of materials science during the past decades. Here, we review the present understanding of film growth processes—nucleation, coalescence, competitive grain growth, and recrystallization—and their role in microstructural evolution as a function of deposition variables including temperature, the presence of reactive species, and the use of low-energy ion irradiation during growth.

Graphite Oxide: Chemical Reduction to Graphite and Surface Modification with Primary Aliphatic Amines and Amino Acids

Abstract: The chemical reduction of graphite oxide (GO) to graphite by either NaBH4 or hydroquinone and also its surface modification with neutral, primary aliphatic amines and amino acids are described. Treatment of GO with NaBH4 leads to turbostatic graphite that upon calcination under an inert atmosphere is transformed to highly ordered graphitic carbon, while the reduction with hydroquinone yields directly crystalline graphite under soft thermal conditions. On account of the surface-exposed epoxy groups present in the GO solid, its surface modification with neutral, primary aliphatic amines or amine-containing molecules (amino acids and aminosiloxanes) takes place easily through the corresponding nucleophilic substitution reactions. In this way, valuable GO derivatives can be obtained, like molecular pillared GO, organically modified GO affording in organic solvents stable organosols or hydrophilic GO affording in water stable hydrosols and possessing direct cation exchange sites. The potential combination of s...

Rapid Induction of Distinct Stress Responses after the Release of Singlet Oxygen in Arabidopsis

Abstract: The conditional fluorescent (flu) mutant of Arabidopsis accumulates the photosensitizer protochlorophyllide in the dark. After a dark-to-light shift, the generation of singlet oxygen, a nonradical reactive oxygen species, starts within the first minute of illumination and was shown to be confined to plastids. Immediately after the shift, plants stopped growing and developed necrotic lesions. These early stress responses of the flu mutant do not seem to result merely from physicochemical damage. Peroxidation of chloroplast membrane lipids in these plants started rapidly and led to the transient and selective accumulation of a stereospecific and regiospecific isomer of hydroxyoctadecatrieonic acid, free (13S)-HOTE, that could be attributed almost exclusively to the enzymatic oxidation of linolenic acid. Within the first 15 min of reillumination, distinct sets of genes were activated that were different from those induced by superoxide/hydrogen peroxide. Collectively, these results demonstrate that singlet oxygen does not act primarily as a toxin but rather as a signal that activates several stress-response pathways. Its biological activity in Arabidopsis exhibits a high degree of specificity that seems to be derived from the chemical identity of this reactive oxygen species and/or the intracellular location at which it is generated.

A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes

Abstract: A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different Type II enzymes now identified and provides a system for naming the putative genes found by sequence analysis of microbial genomes.

Transition of somatic plant cells to an embryogenic state

Abstract: Under appropriate in vivo or in vitro conditions, certain somatic plant cells have the capability to initiate embryogenic development (somatic embryogenesis). Somatic embryogenesis provides an unique experimental model to understand the molecular and cellular bases of developmental plasticity in plants. In the last few years, the application of modern experimental techniques, as well as the characterization of Arabidopsis embryogenesis mutants, have resulted in the accumulation of novel data about the acquisition of embryogenic capabilities by somatic plant cells. In this review, we summarize relevant experimental observations that can contribute to the description and definition of a transitional state of somatic cells induced to form totipotent, embryogenic cells. During this somatic-to-embryogenic transition, cells have to dedifferentiate, activate their cell division cycle and reorganize their physiology, metabolism and gene expression patterns. The roles of stress, endogenous growth regulators and chromatin remodelling in the coordinated reorganization of the cellular state are especially emphasized.

Genetic content and evolution of adenoviruses.

Abstract: This review provides an update of the genetic content, phylogeny and evolution of the family Adenoviridae. An appraisal of the condition of adenovirus genomics highlights the need to ensure that public sequence information is interpreted accurately. To this end, all complete genome sequences available have been reannotated. Adenoviruses fall into four recognized genera, plus possibly a fifth, which have apparently evolved with their vertebrate hosts, but have also engaged in a number of interspecies transmission events. Genes inherited by all modern adenoviruses from their common ancestor are located centrally in the genome and are involved in replication and packaging of viral DNA and formation and structure of the virion. Additional niche-specific genes have accumulated in each lineage, mostly near the genome termini. Capture and duplication of genes in the setting of a ‘leader–exon structure’, which results from widespread use of splicing, appear to have been central to adenovirus evolution. The antiquity of the pre-vertebrate lineages that ultimately gave rise to the Adenoviridae is illustrated by morphological similarities between adenoviruses and bacteriophages, and by use of a protein-primed DNA replication strategy by adenoviruses, certain bacteria and bacteriophages, and linear plasmids of fungi and plants.

Dynamic, yet structured: The cell membrane three decades after the Singer-Nicolson model

Abstract: The fluid mosaic membrane model proved to be a very useful hypothesis in explaining many, but certainly not all, phenomena taking place in biological membranes. New experimental data show that the compartmentalization of membrane components can be as important for effective signal transduction as is the fluidity of the membrane. In this work, we pay tribute to the Singer-Nicolson model, which is near its 30th anniversary, honoring its basic features, "mosaicism" and "diffusion," which predict the interspersion of proteins and lipids and their ability to undergo dynamic rearrangement via Brownian motion. At the same time, modifications based on quantitative data are proposed, highlighting the often genetically predestined, yet flexible, multilevel structure implementing a vast complexity of cellular functions. This new "dynamically structured mosaic model" bears the following characteristics: emphasis is shifted from fluidity to mosaicism, which, in our interpretation, means nonrandom codistribution patterns of specific kinds of membrane proteins forming small-scale clusters at the molecular level and large-scale clusters (groups of clusters, islands) at the submicrometer level. The cohesive forces, which maintain these assemblies as principal elements of the membranes, originate from within a microdomain structure, where lipid-lipid, protein-protein, and protein-lipid interactions, as well as sub- and supramembrane (cytoskeletal, extracellular matrix, other cell) effectors, many of them genetically predestined, play equally important roles. The concept of fluidity in the original model now is interpreted as permissiveness of the architecture to continuous, dynamic restructuring of the molecular- and higher-level clusters according to the needs of the cell and as evoked by the environment.

Genetic algorithms in computer aided design

Abstract: Design is a complex engineering activity, in which computers are more and more involved. The design task can often be seen as an optimization problem in which the parameters or the structure describing the best quality design are sought. Genetic algorithms constitute a class of search algorithms especially suited to solving complex optimization problems. In addition to parameter optimization, genetic algorithms are also suggested for solving problems in creative design, such as combining components in a novel, creative way. Genetic algorithms transpose the notions of evolution in Nature to computers and imitate natural evolution. Basically, they find solution(s) to a problem by maintaining a population of possible solutions according to the ‘survival of the fittest’ principle. We present here the main features of genetic algorithms and several ways in which they can solve difficult design problems. We briefly introduce the basic notions of genetic algorithms, namely, representation, genetic operators, fitness evaluation, and selection. We discuss several advanced genetic algorithms that have proved to be efficient in solving difficult design problems. We then give an overview of applications of genetic algorithms to different domains of engineering design.

GARCH processes: structure and estimation

Abstract: We study the structure of a GARCH$(p,q)$ sequence. We show that the conditional variance can be written as an infinite sum of the squares of the previous observations and that the representation is unique. We prove the consistency and asymptotic normality of the quasi-maximum likelihood estimator of the parameters of the GARCH$(p,q)$ sequence under mild conditions.

PSORT-B: Improving protein subcellular localization prediction for Gram-negative bacteria.

Abstract: Automated prediction of bacterial protein subcellular localization is an important tool for genome annotation and drug discovery. PSORT has been one of the most widelyused computational methods for such bacterial protein analysis; however, it has not been updated since it was introduced in 1991. In addition, neither PSORT nor anyof the other computational methods available make predictions for all five of the localization sites characteristic of Gram-negative bacteria. Here we present PSORT-B, an updated version of PSORT for Gram-negative bacteria, which is available as a web-based application at http://www.psort.org. PSORT-B examines a given protein sequence for amino acid composition, similarityto proteins of known localization, presence of a signal peptide, transmembrane alpha-helices and motifs corresponding to specific localizations. A probabilistic method integrates these analyses, returning a list of five possible localization sites with associated probabilityscores. PSORT-B, designed to favor high precision (specificity) over high recall (sensitivity), attained an overall precision of 97% and recall of 75% in 5-fold cross-validation tests, using a dataset we developed of 1443 proteins of experimentallyknown localization. This dataset, the largest of its kind, is freelyavailable, along with the PSORT-B source code (under GNU General Public License).

A new classification scheme of science fields and subfields designed for scientometric evaluation purposes

Abstract: A two-level hierarchic system of fields and subfields of the sciences, social sciences and arts & humanities is proposed. The system was specifically designed for scientometric (evaluation) purposes with the ultimate goal of classifying every single document into a well-defined category. This goal was achieved using a three-step iterative process. The basic concepts and some preliminary results are presented.

Expression and function of Toll-like receptors 2 and 4 in human keratinocytes.

Abstract: Keratinocytes have the ability to kill pathogenic fungi and bacteria by producing antimicrobial substances. Recent studies suggest that microbial components use signaling molecules of the human Toll-like receptor (TLR) family to transduce signals in various cells. Here we provide evidence that keratinocytes express both TLR2 and TLR4 at the mRNA and protein levels, and show that TLR2 and TLR4 are present in the normal human epidermis in vivo and that their expression is regulated by microbial components. The expression of myeloid differentiation protein gene (MyD88), which is involved in the signaling pathway of many TLR, was also demonstrated in keratinocytes. LPS + IFN-gamma increased the expression of TLR2 and TLR4 50- and 5-fold respectively. Treatment of keratinocytes with Candida albicans, mannan, Mycobacterium tuberculosis or LPS with IFN-gamma resulted in the activation and nuclear translocation of NF-kappaB. Inhibition of NF-kappaB blocked the Candida-killing activity of keratinocytes, suggesting that the antimicrobial effect of keratinocytes requires NF-kappaB activation. LPS + IFN-gamma, C. albicans (4 Candida/KC), peptidoglycan (1 micro g/ml) or M. tuberculosis extract significantly increased IL-8 gene expression after 3 h of treatment (P < 0.05). The increases over the 0-h level were 15-, 8-, 10.8- and 7-fold, respectively. The microbial compound-induced increase in IL-8 gene expression could be inhibited by anti-TLR2 and anti-TLR4 neutralizing antibodies, suggesting that TLRs are involved in the pathogen-induced expression of this pro-inflammatory cytokine. Our findings stress the importance of the role of keratinocytes as a component of innate immunity.

Identified sources and targets of slow inhibition in the neocortex.

Abstract: There are two types of inhibitory postsynaptic potentials in the cerebral cortex. Fast inhibition is mediated by ionotropic gamma-aminobutyric acid type A (GABA(A)) receptors, and slow inhibition is due to metabotropic GABA(B) receptors. Several neuron classes elicit inhibitory postsynaptic potentials through GABA(A) receptors, but possible distinct sources of slow inhibition remain unknown. We identified a class of GABAergic interneurons, the neurogliaform cells, that, in contrast to other GABA-releasing cells, elicited combined GABA(A) and GABA(B) receptor-mediated responses with single action potentials and that predominantly targeted the dendritic spines of pyramidal neurons. Slow inhibition evoked by a distinct interneuron in spatially restricted postsynaptic compartments could locally and selectively modulate cortical excitability.

Revealed comparative advantage and competitiveness in Hungarian agri-food sectors

Abstract: We examine the competitiveness of Hungarian agriculture and food processing, in relation to that of the EU, based on four indices of revealed comparative advantage, using highly disaggregate data for the period 1992 to 1998. Consistency tests suggest that the indices are less satisfactory as cardinal measures, but are useful in identifying the demarcation between comparative advantage and comparative disadvantage. Hungary is shown to have a comparative advantage in a range of agri-food products, including animals and meat. This complements the findings of those studies that have used price and cost based approaches in identifying competitiveness in cereals and crops. Results indicate that the RCA indices, when interpreted as a binary measure, have remained surprisingly stable during the period of transition, although there is evidence of a weakening in the level of comparative advantage as revealed in the Balassa index.

Light-dependent induction of proline biosynthesis by abscisic acid and salt stress is inhibited by brassinosteroid in Arabidopsis

Abstract: Osmotic stress-induced accumulation of proline, an important protective osmolyte in higher plants, is dependent on the expression of delta1-pyrroline-5-carboxylate synthase (P5CS) and proline dehydrogenase (PDH) enzymes that catalyze the rate-limiting steps of proline biosynthesis and degradation, respectively. Proline metabolism is modulated by differential regulation of organ specific expression of PDH and duplicated P5CS genes in Arabidopsis. Stimulation of proline synthesis by abscisic acid (ABA) and salt stress correlates with a striking activation of P5CS1 expression. By contrast, P5CS2 is only weakly induced, whereas PDH is inhibited to different extent by ABA and salt stress in shoots and roots of light-grown plants. Proline accumulation and light-dependent induction of PSCS1 by ABA and salt stress is inhibited in dark-adapted plants. During dark adaptation P5CS2 is also down-regulated, whereas PDH expression is significantly enhanced in shoots. The inhibitory effect of dark adaptation on PSCS1 is mimicked by the steroid hormone brassinolide. However, brassinolide fails to stimulate PDH, and inhibits P5CS2 only in shoots. Proline accumulation and induction of P5CS1 transcription are simultaneously enhanced in the ABA-hypersensitive prl1 and brassinosteroid-deficient det2 mutants, whereas P5CS2 shows enhanced induction by ABA and salt only in the det2 mutant. In comparison, the prl1 mutation reduces the basal level of PDH expression, whereas the det2 mutation enhances the inhibition of PDH by ABA. Regulation of P5CS1 expression thus appears to play a principal role in controlling proline accumulation stimulated by ABA and salt stress in Arabidopsis.

The Developmental Roots of Borderline Personality Disorder in Early Attachment Relationships: A Theory and Some Evidence

Abstract: The paper suggests a way of understanding borderline personality disorder in terms of the failure of a secure base. We begin with an account of optimal self-development in a secure attachment context, highlighting the importance of the caregiver's ability to help the small child think about his own and others' minds. This optimal self-development is crucial in developing the child's capacity for mentalization, which can enhance his resilience in the face of later trauma. We discuss the impact of attachment trauma in later development, arguing that the extent of this impact depends on how well early attachment relationships facilitated the capacity for mentalization. We identify some of the consequences for the representations of the internal world of a failure of mentalization that may follow trauma in individuals made vulnerable by genetic predisposition or disorganized early attachment. We link these features to the clinical presentation associated with borderline personality organization. Finally, some...

Analysis of Ras-induced overproliferation in Drosophila hemocytes.

Abstract: We use the Drosophila melanogaster larval hematopoietic system as an in vivo model for the genetic and functional genomic analysis of oncogenic cell overproliferation. Ras regulates cell proliferation and differentiation in multicellular eukaryotes. To further elucidate the role of activated Ras in cell overproliferation, we generated a collagen promoter-Gal4 strain to overexpress Ras V12 in Drosophila hemocytes. Activated Ras causes a dramatic increase in the number of circulating larval hemocytes (blood cells), which is caused by cellular overproliferation. This phenotype is mediated by the Raf/MAPK pathway. The mutant hemocytes retain the ability to phagocytose bacteria as well as to differentiate into lamellocytes. Microarray analysis of hemocytes overexpressing Ras V12 vs. Ras + identified 279 transcripts that are differentially expressed threefold or more in hemocytes expressing activated Ras. This work demonstrates that it will be feasible to combine genetic and functional genomic approaches in the Drosophila hematopoietic system to systematically identify oncogene-specific downstream targets.

Intrinsically unstructured proteins evolve by repeat expansion.

Abstract: The proportion of the genome encoding intrinsically unstructured proteins increases with the complexity of organisms, which demands specific mechanism(s) for generating novel genetic material of this sort. Here it is suggested that one such mechanism is the expansion of internal repeat regions, i.e., coding micro- and minisatellites. An analysis of 126 known unstructured sequences shows the preponderance of repeats: the percentage of proteins with tandemly repeated short segments is much higher in this class (39%) than earlier reported for all Swiss-Prot (14%), yeast (18%) or human (28%) proteins. Furthermore, prime examples, such as salivary proline-rich proteins, titin, eukaryotic RNA polymerase II, the prion protein and several others, demonstrate that the repetitive segments carry fundamental function in these proteins. In addition, their repeat numbers show functionally significant interspecies variation and polymorphism, which underlines that these regions have been shaped by intense evolutionary activity. In all, the major point of this paper is that the genetic instability of repetitive regions combined with the structurally and functionally permissive nature of unstructured proteins has powered the extension and possible functional expansion of this newly recognized protein class.

Characterization of the 820-nm transmission signal paralleling the chlorophyll a fluorescence rise (OJIP) in pea leaves

Abstract: Monitoring transmission changes at 820 nm, a measure of the redox states of plastocyanin (PC) and P700, is a good complementary technique for chlorophyll (chl) a fluorescence induction measurements. A thorough characterization of the properties of the 820-nm transmission kinetics during the first second after a dark-to-light transition is provided here for pea (Pisum sativum L.) leaves. The data indicate that plastocyanin in a dark-adapted leaf is in the reduced state. Three photosystem I (PSI)-related components, PC, P700 and ferredoxin, can contribute to the 820-nm transmission signal. The contribution of ferredoxin, however, is only approximately 5%, thus, it can be neglected for further analysis. Here, we show that by monitoring the sequential oxidation of PC and P700 during a far-red pulse and analysing the re-reduction kinetics it is possible to assign the three re-reduction components to PC (τ = 7-14 s) and P700 (τ = 35-55 ms and 1.2-1.6 s). Our data indicate that the faster re-reduction phase (τ =35-55 ms) may represent a recombination reaction between P700+ and the acceptor side of PSI. This information made it possible to show that the ratio between the potential contributions of PC : P700 is 50 : 50 in pea and Camellia leaves and 40 : 60 in sugar beet leaves.

Directed and elliptic flow of charged pions and protons in Pb + Pb collisions at 40A and 158A GeV

Abstract: Directed and elliptic flow measurements for charged pions and protons are reported as a function of transverse momentum, rapidity, and centrality for 40A and 158A GeV Pb+Pb collisions, as recorded by the NA49 detector. Both the standard method of correlating particles with an event plane and the cumulant method of studying multiparticle correlations are used. In the standard method the directed flow is corrected for conservation of momentum. In the cumulant method elliptic flow is reconstructed from genuine four-, six-, and eight-particle correlations, showing the first unequivocal evidence for collective motion in A+A collisions at SPS energies.

NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.

Abstract: The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.

Central role for Rho in TGF-β1-induced α-smooth muscle actin expression during epithelial-mesenchymal transition

Abstract: New research suggests that, during tubulointerstitial fibrosis, α-smooth muscle actin (SMA)-expressing mesenchymal cells might derive from the tubular epithelium via epithelial-mesenchymal transiti...