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Showing papers by "University of Fribourg published in 2001"


Journal ArticleDOI
15 Nov 2001-Nature
TL;DR: Recent developments in the search for innovative materials with high hydrogen-storage capacity are presented.
Abstract: Mobility — the transport of people and goods — is a socioeconomic reality that will surely increase in the coming years. It should be safe, economic and reasonably clean. Little energy needs to be expended to overcome potential energy changes, but a great deal is lost through friction (for cars about 10 kWh per 100 km) and low-efficiency energy conversion. Vehicles can be run either by connecting them to a continuous supply of energy or by storing energy on board. Hydrogen would be ideal as a synthetic fuel because it is lightweight, highly abundant and its oxidation product (water) is environmentally benign, but storage remains a problem. Here we present recent developments in the search for innovative materials with high hydrogen-storage capacity.

7,414 citations


Journal ArticleDOI
05 Jul 2001-Nature
TL;DR: The data indicate that the use of analytical tests derived from formal behavioural learning theory provides a powerful approach for studying the role of single neurons in learning.
Abstract: According to contemporary learning theories, the discrepancy, or error, between the actual and predicted reward determines whether learning occurs when a stimulus is paired with a reward. The role of prediction errors is directly demonstrated by the observation that learning is blocked when the stimulus is paired with a fully predicted reward. By using this blocking procedure, we show that the responses of dopamine neurons to conditioned stimuli was governed differentially by the occurrence of reward prediction errors rather than stimulus‐reward associations alone, as was the learning of behavioural reactions. Both behavioural and neuronal learning occurred predominantly when dopamine neurons registered a reward prediction error at the time of the reward. Our data indicate that the use of analytical tests derived from formal behavioural learning theory provides a powerful approach for studying the role of single neurons in learning. Classic theories assume that predictive learning occurs whenever a stimulus is paired with a reward or punishment 1,2 . However, more recent analyses of associative learning argue that simple temporal contiguity between a stimulus and a reinforcer is not sufficient for learning and that a discrepancy between the reinforcer that is predicted by a stimulus and the actual reinforcer is also required 3‐6 . This discrepancy can be characterized as a ‘prediction error’ 7 . Presentations of surprising or unpredicted reinforcers generate positive prediction errors, and thereby support learning, whereas omissions of predicted reinforcers generate negative prediction errors and lead to reduction or extinction of learned behaviour. Expected reinforcers do not generate prediction errors and therefore fail to support further learning even when the stimulus is consistently paired with the reinforcer. Modelling studies have shown that neuronal messages encoding prediction errors can act as explicit teaching signals for modifying the synaptic connections that underlie associative learning 8‐17 .

972 citations


Journal ArticleDOI
14 Jun 2001-Nature
TL;DR: The results support the concept of a jamming phase diagram for attractive colloidal particles, providing a unifying link between the glass transition, gelation and aggregation.
Abstract: A wide variety of systems, including granular media, colloidal suspensions and molecular systems, exhibit non-equilibrium transitions from a fluid-like to a solid-like state, characterized solely by the sudden arrest of their dynamics. Crowding or jamming of the constituent particles traps them kinetically, precluding further exploration of the phase space1. The disordered fluid-like structure remains essentially unchanged at the transition. The jammed solid can be refluidized by thermalization, through temperature or vibration, or by an applied stress. The generality of the jamming transition led to the proposal2 of a unifying description, based on a jamming phase diagram. It was further postulated that attractive interactions might have the same effect in jamming the system as a confining pressure, and thus could be incorporated into the generalized description. Here we study experimentally the fluid-to-solid transition of weakly attractive colloidal particles, which undergo markedly similar gelation behaviour with increasing concentration and decreasing thermalization or stress. Our results support the concept of a jamming phase diagram for attractive colloidal particles, providing a unifying link between the glass transition3, gelation4,5 and aggregation6,7,8.

827 citations


Journal ArticleDOI
08 Nov 2001-Nature
TL;DR: It is demonstrated that projection neurons are prespecified by lineage and birth order to form synapses with specific incoming ORN axons, and therefore to carry specific olfactory information, which could be used to hardwire the fly's Olfactory system, enabling stereotyped behavioural responses to odorants.
Abstract: In Drosophila and mice, olfactory receptor neurons (ORNs) expressing the same receptors have convergent axonal projections to specific glomerular targets in the antennal lobe/olfactory bulb, creating an odour map in this first olfactory structure of the central nervous system1,2,3. Projection neurons of the Drosophila antennal lobe send dendrites into glomeruli and axons to higher brain centres4, thereby transferring this odour map further into the brain. Here we use the MARCM method5 to perform a systematic clonal analysis of projection neurons, allowing us to correlate lineage and birth time of projection neurons with their glomerular choice. We demonstrate that projection neurons are prespecified by lineage and birth order to form synapses with specific incoming ORN axons, and therefore to carry specific olfactory information. This prespecification could be used to hardwire the fly's olfactory system, enabling stereotyped behavioural responses to odorants. Developmental studies lead us to hypothesize that recognition molecules ensure reciprocally specific connections of ORNs and projection neurons. These studies also imply a previously unanticipated role for precise dendritic targeting by postsynaptic neurons in determining connection specificity.

410 citations



Journal ArticleDOI
TL;DR: The authors conclude that the mammalian Per genes are not only light-responsive components of the circadian oscillator but also are involved in resetting of thecircadian clock.
Abstract: Mammalian Per1 and Per2 genes are involved in the mechanism of the circadian clock and are inducible by light. A light pulse can evoke a change in the onset of wheel-running activity in mice by shifting the onset of activity to earlier times (phase advance) or later times (phase delays) thereby advancing or delay- ing the clock (clock resetting). To assess the role of mouse Per (mPer) genes in cir- cadian clock resetting, mice carrying mutant mPer1 or mPer2 genes were tested for responses to a light pulse at ZT 14 and ZT 22, respectively. The authors found that mPer1 mutants did not advance and mPer2 mutants did not delay the clock. They conclude that the mammalian Per genes are not only light-responsive com- ponents of the circadian oscillator but also are involved in resetting of the circa- dian clock.

390 citations


Journal ArticleDOI
TL;DR: The findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training, and fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O(2) uptake or maximal power output.
Abstract: This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O2 uptake (8.3–13.1%) and maximal power output (11.4–20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the α-subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1α736, a splice variant of HIF-1α newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1α. Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in h...

382 citations


Journal ArticleDOI
TL;DR: The dopamine reward prediction error signal may cooperate with these reward perception signals during the learning and performance of behavioral reactions to motivating environmental stimuli.
Abstract: Dopamine projections from the midbrain to the striatum and frontal cortex are involved in behavioral reactions controlled by rewards, as inferred from deficits in parkinsonism, schizophrenia, and drug addiction. Recent experiments have shown that dopamine neurons are not directly modulated in relation to movements. Rather, they appear to code the rewarding aspects of environmental stimuli. They show short, phasic increases of activity following primary food and liquid rewards ("unconditioned stimuli") and conditioned, reward-predicting stimuli of visual, auditory, and somatosensory modalities. They also display smaller activation-depression sequences after stimuli resembling rewards and after novel or particularly intense stimuli. Rewards are only reported as far as they occur differently than predicted. According to learning theories, a "prediction error" message may constitute a powerful teaching signal for behavior and learning. The phasic reward message is different from the more tonic enabling function of dopamine that is deficient in Parkinson's disease, indicating that dopamine neurons subserve different functions at different time scales. Neurons in other brain structures, such as the striatum, orbitofrontal cortex, and amygdala, code the quality, quantity, and preference of rewards. The dopamine reward prediction error signal may cooperate with these reward perception signals during the learning and performance of behavioral reactions to motivating environmental stimuli.

331 citations


Journal ArticleDOI
TL;DR: Evidence is presented that the protective effect of BABA is due to a potentiation of natural defense mechanisms against biotic and abiotic stresses and a mutational approach based on BABA-induced female sterility in Arabidopsis is described.
Abstract: Thehe broad sprectrum protective effect of the non-protein amino acid β-aminobutyric acid (BABA) against numerous plant diseases has been well-documented in the literature. Here, we present an overview of BABA-induced protection in various pathosystems. Contriidictory reports concerning the mechanism of action underlying this type of protection incited us to take advantage of Arabidopsis/pathogen interactions as model systems to investigate the action of BABA at the genetic and molecular level. We present evidence that the protective effect of BABA is due to a potentiation of natural defense mechanisms against biotic and abiotic stresses. In order to dissect the pathways involved in potentiation by BABA describe the use of a mutational approach based on BABA-induced female sterility in Arabidopsis.

321 citations


Journal ArticleDOI
TL;DR: It is suggested that glucosinolate-derived antimicrobial ITCs can play a role in the protection of Arabidopsis against particular pathogens.
Abstract: Crude aqueous extracts from Arabidopsis leaves were subjected to chromatographic separations, after which the different fractions were monitored for antimicrobial activity using the fungus Neurospora crassa as a test organism. Two major fractions were obtained that appeared to have the same abundance in leaves from untreated plants versus leaves from plants challenge inoculated with the fungus Alternaria brassicicola. One of both major antimicrobial fractions was purified to homogeneity and identified by 1H nuclear magnetic resonance, gas chromatography/electron impact mass spectrometry, and gas chromatography/chemical ionization mass spectrometry as 4-methylsulphinylbutyl isothiocyanate (ITC). This compound has previously been described as a product of myrosinase-mediated breakdown of glucoraphanin, the predominant glucosinolate in Arabidopsis leaves. 4-Methylsulphinylbutyl ITC was found to be inhibitory to a wide range of fungi and bacteria, producing 50% growth inhibition in vitro at concentrations of 28 microM for the most sensitive organism tested (Pseudomonas syringae). A previously identified glucosinolate biosynthesis mutant, gsm1-1, was found to be largely deficient in either of the two major antimicrobial compounds, including 4-methylsulphinylbutyl ITC. The resistance of gsm1-1 was compared with that of wild-type plants after challenge with the fungi A. brassicicola, Plectosphaerella cucumerina, Botrytis cinerea, Fusarium oxysporum, or Peronospora parasitica, or the bacteria Erwinia carotovora or P. syringae. Of the tested pathogens, only F. oxysporum was found to be significantly more aggressive on gsm1-1 than on wild-type plants. Taken together, our data suggest that glucosinolate-derived antimicrobial ITCs can play a role in the protection of Arabidopsis against particular pathogens.

317 citations


Journal ArticleDOI
TL;DR: BA protected mutants defective in the jasmonate and ethylene pathways, but was inactive in plants impaired in the systemic acquired resistance transduction pathway, suggesting that SA-dependent signaling is down-regulated after infection by B. cinerea.
Abstract: The non-protein amino acid β-aminobutyric acid (BABA) protects numerous plants against various pathogens. Protection of Arabidopsis plants against virulent pathogens involves the potentiation of pathogen-specific defense responses. To extend the analysis of the mode of action of BABA to necrotrophs we evaluated the effect of this chemical on Arabidopsis plants infected with the gray mold fungus Botrytis cinerea . BABA-treated Arabidopsis were found to be less sensitive to two different strains of this pathogen. BABA protected mutants defective in the jasmonate and ethylene pathways, but was inactive in plants impaired in the systemic acquired resistance transduction pathway. Treatments with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S -methyl ester, a functional analog of salicylic acid (SA), also markedly reduced the level of infection. Moreover, BABA potentiated mRNA accumulation of the SA-associated PR-1, but not the jasmonate/ethylene-dependent PDF1.2 gene. Thus, besides jasmonate/ethylene-dependent defense responses, SA-dependent signaling also contributes to restrict B. cinerea infection in Arabidopsis. Our results also suggest that SA-dependent signaling is down-regulated after infection by B. cinerea . The observed up-regulation of the PDF1.2 gene in mutants defective in the SA-dependent signaling pathway points to a cross-talk between SA- and jasmonate/ethylene-dependent signaling pathways during pathogen ingress.

Journal ArticleDOI
TL;DR: It is shown that microsomes or detergent extracts from lag1Δlac1ΓΔ double mutants lack an activity transferring C26 fatty acids from C26‐coenzyme A onto dihydrosphingosine or phytosphingoine.
Abstract: Lag1p and Lac1p are two highly homologous membrane proteins of the endoplasmic reticulum (ER). When both genes are deleted, cells cannot transport glycosylphosphatidylinositol (GPI)-anchored proteins from the ER to the Golgi at a normal rate. Here we show that microsomes or detergent extracts from lag1Δlac1Δ double mutants lack an activity transferring C26 fatty acids from C26-coenzyme A onto dihydrosphingosine or phytosphingosine. As a consequence, in intact cells, the normal ceramides and inositolphosphorylceramides are drastically reduced. lag1Δlac1Δ cells compensate for the lack of normal sphingolipids by making increased amounts of C26 fatty acids, which become incorporated into glycerophospholipids. They also contain 20- to 25-fold more free long chain bases than wild type and accumulate very large amounts of abnormally polar ceramides. They make small amounts of abnormal mild base-resistant inositolphospholipids. The lipid remodelling of GPI-anchored proteins is severely compromised in lag1Δlac1Δ double mutants since only few and mostly abnormal ceramides are incorporated into the GPI anchors. The participation of Lag1p and Lac1p in ceramide synthesis may explain their role in determining longevity.

Journal ArticleDOI
TL;DR: The data suggest that the expectation of an upcoming liquid reward may influence a fraction of task-related neurons in the anterior striatum, and apparently the information about the expected reward is incorporated into the neuronal activity related to the behavioral reaction leading to the reward.
Abstract: This study investigated how different expected rewards influence behavior-related neuronal activity in the anterior striatum. In a spatial delayed-response task, monkeys reached for a left or right target and obtained a small quantity of one of two juices (apple, grenadine, orange, lemon, black currant, or raspberry). In each trial, an initial instruction picture indicated the behavioral target and predicted the reward. Nonmovement trials served as controls for movement relationships. Consistent preferences in special reward choice trials and differences in anticipatory licks, performance errors, and reaction times indicated that animals differentially expected the rewards predicted by the instructions. About 600 of >2,500 neurons in anterior parts of caudate nucleus, putamen, and ventral striatum showed five forms of task-related activations, comprising responses to instructions, spatial or nonspatial activations during the preparation or execution of the movement, and activations preceding or following the rewards. About one-third of the neurons showed different levels of task-related activity depending on which liquid reward was predicted at trial end. Activations were either higher or lower for rewards that were preferred by the animals as compared with nonpreferred rewards. These data suggest that the expectation of an upcoming liquid reward may influence a fraction of task-related neurons in the anterior striatum. Apparently the information about the expected reward is incorporated into the neuronal activity related to the behavioral reaction leading to the reward. The results of this study are in general agreement with an account of goal-directed behavior according to which the outcome should be represented already at the time at which the behavior toward the outcome is performed.

Journal ArticleDOI
TL;DR: Observations indicate that nuclear translocation of GAPDH may play a role in apoptosis and oxidative stress, probably related to the activity ofGAPDH as a DNA repair enzyme or as a nuclear carrier for pro-apoptotic molecules.
Abstract: Recent studies indicating a role of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in apoptosis or oxidative stress has been reported. Using confocal laser-scanning microscopy, we have investigated the cellular distribution of GAPDH in central nervous system (CNS)-derived cells (neuroblastoma mNB41A3), in non-CNS derived cells (R6 fibroblast) and in an apoptosis-resistant Bcl2 overexpressing cell line (R6-Bcl2). Induction of apoptosis by staurosporine or MG132 and oxidative stress by H(2)O(2) or FeCN enhanced the nuclear translocation of endogenous GAPDH in all cell types, as detected by immunocytochemistry. In apoptotic cells, GAPDH expression is three times higher than in non-apoptotic cells. Consistent with a role for GAPDH in apoptosis, overexpression of a GAPDH-green fluorescent protein (GAPDH-GFP) hybrid increased nuclear import of GAPDH-GFP into transfected cells and the number of apoptotic cells, and made them more sensitive to agents that induce apoptosis. Bcl2 overexpression prevents nuclear translocation of GAPDH and apoptosis in untransfected cells, but not in transfected cells that overexpress GAPDH-GFP. Our observations indicate that nuclear translocation of GAPDH may play a role in apoptosis and oxidative stress, probably related to the activity of GAPDH as a DNA repair enzyme or as a nuclear carrier for pro-apoptotic molecules.

Journal ArticleDOI
TL;DR: It is argued that the direct PN-to-lateral protocerebrum pathway is necessary and sufficient to process these experience-independent behaviors in fruit flies and suggests a role of volatile attractive female pheromones in Drosophila.
Abstract: We have studied the function of the major central olfactory pathway in fruit flies. Key elements of this pathway, the projection neurons (PNs), connect the antennal lobes with the lateral protocerebrum both directly and indirectly, the latter via the mushroom bodies (MBs). Transgenic expression of tetanus toxin in the majority of PNs and few MB neurons leads to defects in odor detection and male courtship. Considering behavioral data from flies lacking MBs, our results argue that the direct PN-to-lateral protocerebrum pathway is necessary and sufficient to process these experience-independent behaviors. Moreover, the involvement of an olfactory pathway in male courtship suggests a role of volatile attractive female pheromones in Drosophila.

Journal ArticleDOI
TL;DR: It is demonstrated that the arm to leg coordination observed in the walking human is also present during other human locomotor activities and the characteristics of this coordination correspond to those of a system of two coupled oscillators like that underlying quadruped locomotion.
Abstract: In walking humans, arm to leg coordination is a well established phenomenon. The origin of this coordination, however, remains a matter for debate. It could derive from the intrinsic organisation of the human CNS, but it could also consist of a movement induced epiphenomenon. In order to establish which of these alternatives applies, we recorded arm and leg movements as well as their muscle activities during walking, creeping on all fours and swimming. The relationship between arm and leg cycle frequency observed under these various conditions was then investigated. We found that during walking, creeping on all fours or swimming, arm and leg movements remain frequency locked with a fixed relationship of 1/1, 2/1, 3/1, 4/1 or 5/1. When movements of the legs are slowed by flippers, the frequency relationship may skip to a different value, but the coordination is preserved. Furthermore, minimising the mechanical interactions between the limbs does not abolish coordination. These findings demonstrate that the arm to leg coordination observed in the walking human is also present during other human locomotor activities. The characteristics of this coordination correspond to those of a system of two coupled oscillators like that underlying quadruped locomotion.

Journal ArticleDOI
TL;DR: The results are in accordance with an explanation of the face-inversion effect in which the disruption of configural facial information plays the critical role in memory for faces, and in which configural information corresponds to spatial information that is processed in a way which is sensitive to local properties of the facial features involved.
Abstract: When faces are turned upside down, recognition is known to be severely disrupted. This effect is thought to be due to disruption of configural processing. Recently, Leder and Bruce (2000, Quarterly Journal of Experimental Psychology A 53 513-536) argued that configural information in face processing consists at least partly of locally processed relations between facial elements. In three experiments we investigated whether a local relational feature (the interocular distance) is processed differently in upside-down versus upright faces. In experiment 1 participants decided in which of two sequentially presented photographic faces the interocular distance was larger. The decision was more difficult in upside-down presentation. Three different conditions were used in experiment 2 to investigate whether this deficit depends upon parts of the face beyond the eyes themselves; displays showed the eye region alone, the eyes and nose, or the eyes and nose and mouth. The availability of additional features did not interact with the inversion effect which was observed strongly even when the eyes were shown in isolation. In experiment 3 all eyes were turned upside down in the inverted face condition as in the Thatcher illusion (Thompson, 1980 Perception 9 483-484). In this case no inversion effect was found. These results are in accordance with an explanation of the face-inversion effect in which the disruption of configural facial information plays the critical role in memory for faces, and in which configural information corresponds to spatial information that is processed in a way which is sensitive to local properties of the facial features involved.

Journal ArticleDOI
TL;DR: The reactions occurring locally in the inducer leaf, the systemic signal and reactions in the upper leaf will be briefly reviewed here, with a special emphasis on the role played by salicylic acid in this process.
Abstract: Plants can induce defense reactions to a broad range of pathogens as a result of prior exposure to pathogens, various chemicals or physical stress. Induced resistance is expressed locally, at the site of the infection or systemically, at sites remotely located from the initial infection. The reactions occurring locally in the inducer leaf, the systemic signal and reactions in the upper leaf will be briefly reviewed here, with a special emphasis on the role played by salicylic acid in this process.

Journal ArticleDOI
TL;DR: The present paper traces first, from a historical perspective, the landmark events in the field of thermogenesis that led to the identification of these genes encoding candidate UCP, and addresses the controversies and on-going debate about their physiological importance in adaptive thermogenesis, in lipid oxidation or in oxidative stress.
Abstract: During the past few years, there have been two major developments, if not revolutions, in the field of energy balance and weight regulation. The first at the molecular level, which was catalysed by developments in DNA screening technology together with the mapping of the human genome, has been the tremendous advances made in the identification of molecules that play a role in the control of food intake and metabolic rate. The second, at the systemic level, which centered upon the use of modern technologies or more robust analytical techniques for assessing human energy expenditure in response to starvation and overfeeding, has been the publication of several papers providing strong evidence that adaptive thermogenesis plays a much more important role in the regulation of body weight and body composition than previously thought. Within these same few years, several new members of the mitochondrial carrier protein family have been identified in a variety of tissues and organs. All apparently possess uncoupling properties in genetically-modified systems, with two of them (uncoupling protein (UCP) 2 and UCP3) being expressed in adipose tissues and skeletal muscles, which are generally recognised as important sites for variations in thermogenesis and/or in substrate oxidation. Considered as breakthrough discoveries, the cloning of these genes has generated considerable optimism for rapid advances in our molecular understanding of adaptive thermogenesis, and for the identification of new targets for pharmacological management of obesity and cachexia. The present paper traces first, from a historical perspective, the landmark events in the field of thermogenesis that led to the identification of these genes encoding candidate UCP, and then addresses the controversies and on-going debate about their physiological importance in adaptive thermogenesis, in lipid oxidation or in oxidative stress. The general conclusion is that UCP2 and UCP3 may have distinct primary functions, with UCP3 implicated in regulating the flux of lipid substrates across the mitochondria and UCP2 in the control of mitochondrial generation of reactive oxygen species. The distinct functions of these two UCP1 homologues have been incorporated in a conceptual model to illustrate how UCP2 and UCP3 may act in concert in the overall regulation of lipid oxidation concomitant to the prevention of lipid-induced oxidative damage.

Journal ArticleDOI
TL;DR: It is suggested that AtSNAP33, the first SNAP25 homologue characterized in plants, is involved in diverse membrane fusion processes, including cell plate formation, and that At SNAP33 function in cytokinesis may be replaced partially by other SNAP 25 homologues.
Abstract: Cytokinesis requires membrane fusion during cleavage-furrow ingression in animals and cell plate formation in plants. In Arabidopsis, the Sec1 homologue KEULE (KEU) and the cytokinesis-specific syntaxin KNOLLE (KN) cooperate to promote vesicle fusion in the cell division plane. Here, we characterize AtSNAP33, an Arabidopsis homologue of the t-SNARE SNAP25, that was identified as a KN interactor in a yeast two-hybrid screen. AtSNAP33 is a ubiquitously expressed membrane-associated protein that accumulated at the plasma membrane and during cell division colocalized with KN at the forming cell plate. A T-DNA insertion in the AtSNAP33 gene caused loss of AtSNAP33 function, resulting in a lethal dwarf phenotype. atsnap33 plantlets gradually developed large necrotic lesions on cotyledons and rosette leaves, resembling pathogen-induced cellular responses, and eventually died before flowering. In addition, mutant seedlings displayed cytokinetic defects, and atsnap33 in combination with the cytokinesis mutant keu was embryo lethal. Analysis of the Arabidopsis genome revealed two further SNAP25-like proteins that also interacted with KN in the yeast two-hybrid assay. Our results suggest that AtSNAP33, the first SNAP25 homologue characterized in plants, is involved in diverse membrane fusion processes, including cell plate formation, and that AtSNAP33 function in cytokinesis may be replaced partially by other SNAP25 homologues.

Journal ArticleDOI
TL;DR: Resistance of Arabidopsis against P. porri appears to depend on unknown defence mechanisms that are under the control of PAD2, which is similar to that seen in agronomically important diseases caused by Phytophthora species.
Abstract: 1These two authors have contributed equally to the work. Summary Arabidopsis accessions were screened with isolates of Phytophthora porri originally isolated from other crucifer species. The described Arabidopsis‐Phytophthora pathosystem shows the characteristics of a facultative biotrophic interaction similar to that seen in agronomically important diseases caused by Phytophthora species. In susceptible accessions, extensive colonization of the host tissue occurred and sexual and asexual spores were formed. In incompatible combinations, the plants reacted with a hypersensitive response (HR) and the formation of papillae at the sites of attempted penetration. Defence pathway mutants such as jar1 (jasmonic acid-insensitive), etr1 (ethylene receptor mutant) and ein2 (ethylene-insensitive) remained resistant towards P. porri. However, pad2, a mutant with reduced production of the phytoalexin camalexin, was hyper-susceptible. The accumulation of salicylic acid (SA) and PR1 protein was strongly reduced in pad2. Surprisingly, this lack of SA accumulation does not appear to be the cause of the hyper-susceptibility because interference with SA signalling in nahG plants or sid2 or npr1 mutants had only a minor effect on resistance. In addition, the functional SA analogue benzothiadiazol (BTH) did not induce resistance in susceptible plants including pad2. Similarly, the complete blockage of camalexin biosynthesis in pad3 did not cause susceptibility. Resistance of Arabidopsis against P. porri appears to depend on unknown defence mechanisms that are under the control of PAD2.

Journal ArticleDOI
TL;DR: This review intends to integrate recent data from the Drosophila olfactory system into an up‐to‐date account of the neuronal basis of olfaction, and finds surprising parallels between the Olfactory systems of flies and mammals, and thus underline the usefulness of the fruitfly as an ofactory model system.
Abstract: This review intends to integrate recent data from the Drosophila olfactory system into an up-to-date account of the neuronal basis of olfaction. It focuses on (1) an electron microscopic study that mapped a large proportion of fruitfly olfactory sensilla, (2) large-scale electrophysiological recordings that allowed the classification of the odor response spectra of a complete set of sensilla, (3) the identification and expression patterns of candidate odorant receptors in the olfactory tissues, (4) central projections of neurons expressing a given odorant receptor, (5) an improved glomerular map of the olfactory center, and (6) attempts to exploit the larval olfactory system as a model of reduced cellular complexity. These studies find surprising parallels between the olfactory systems of flies and mammals, and thus underline the usefulness of the fruitfly as an olfactory model system. Both in Drosophila and in mammals, odorant receptor neurons appear to express only one type of receptor. Neurons expressing a given receptor are scattered in the olfactory tissues but their afferents converge onto a few target glomeruli only. This suggests that in both phyla, the periphery is represented in the brain as a chemotopic map. The major difference between mammals and fruitflies refers to the numbers of receptors, neurons, and glomeruli, which are largely reduced in the latter, and particularly in larvae. Yet, if activated in a combinatorial fashion, even this small set of elements could allow discrimination between a vast array of odorants.

Journal ArticleDOI
TL;DR: The results of animal and human studies suggest that dopamine and dopamine-related regions are associated with the integration of motivational information and movement execution and show a similar pattern of reward-related activation in nicotine and opiate addicts.

Journal ArticleDOI
TL;DR: The main finding of this study is that in previously untrained people, training in hypoxia while living at low altitude increases performance in normoxia to the same extent as training innormoxia, but leads to larger increases of aerobic performance variables when measured under hypoxic conditions.
Abstract: This study was undertaken to test the hypothesis that endurance training in hypoxia is superior to training of the same intensity in normoxia. To avoid adaptation to hypoxia, the subjects lived under normoxic conditions when not training. A secondary objective of this study was to compare the effect of high- vs. moderate-intensity training on aerobic performance variables. Thirty-three men without prior endurance training underwent a cycle ergometer training of 6 weeks, 5 d/week, 30 minutes/d. The subjects were assigned to 4 groups, N-high, N-low, H-high and H-low based on the training criteria normoxia (N; corresponding to a training altitude of 600 m), vs. hypoxia (H; training altitude 3850 m) and intensity (high; corresponding to 80% and low: corresponding to 67% of VO2max). VO2max measured in normoxia increased between 8.5 to 11.1%, independent of training altitude or intensity. VO2max measured in hypoxia increased between 2.9 and 7.2%. Hypoxia training resulted in significantly larger increases than normoxia training. Maximal power that subjects could maintain over a thirty-minute period (measured in normoxia or hypoxia) increased from 12.3 - 26.8% independent of training altitude. However, subjects training at high intensity increased performance more than subjects training at a low intensity. Muscle volume of the knee-extensors as measured by magnetic resonance imaging increased significantly in the H-high group only (+ 5.0%). Mitochondrial volume density measured by EM-morphometry in biopsy samples of m. vastus lat. increased significantly in all groups with the highest increase seen in the H-high group (+ 59%). Capillary length density increased significantly in the H-high group only (+ 17.2%). The main finding of this study is that in previously untrained people, training in hypoxia while living at low altitude increases performance in normoxia to the same extent as training in normoxia, but leads to larger increases of aerobic performance variables when measured under hypoxic conditions. Training intensity had no effect on the gain of VO2max. On the level of skeletal muscle tissue, the combination of hypoxia with high training intensity constitutes the most effective stimulus for increasing muscle oxidative capacity.

Journal ArticleDOI
TL;DR: It is demonstrated that murine mast cell responses are exacerbated in vitro and in vivo by autocrine signals, and require functional PI3Kγ, which relays inflammatory signals through various GPCRs, and is thus central to mast cell function.
Abstract: Chronic inflammation and allergy involve the activation of tissue-resident cells and, later on, the invasion of effector cells. We have previously shown that the loss of phosphoinositide 3-kinase (PI3K) gamma impairs chemokine-dependent migration of neutrophils and macrophages both in vitro and in vivo. On the other hand, PI3K gamma is not required either during phagocytic processes or in the activation of bactericidal activities like granule secretion and particle-mediated respiratory burst in neutrophils. Tissue mast cells are key regulators in allergy and inflammation and release histamine upon clustering of their IgE receptors. We have demonstrated that murine mast cell responses are exacerbated in vitro and in vivo by autocrine signals, and require functional PI3K gamma. Adenosine, acting through the A(3) adenosine receptor, as well as other agonists of G(alpha i)-coupled receptors, transiently increased PtdIns(3,4,5) P (3) exclusively via PI3K gamma. PI3K gamma-derived PtdIns(3,4,5) P (3) was instrumental for initiation of a sustained influx of external Ca(2+) and degranulation. Mice that lacked PI3K gamma did not form oedema when challenged by passive systemic anaphylaxis. PI3K gamma thus relays inflammatory signals through various GPCRs, and is thus central to mast cell function. Taken together, this suggests that pharmaceutical targeting of PI3K gamma might alleviate inflammation at both early and late stages of the allergic response.

Journal ArticleDOI
TL;DR: The presence of infected domestic carnivores can increase E. multilocularis exposure risk in humans, and comparative statistical analyses of seroprevalence and clinical incidence showed an increase in Em2-seropreavalence from 1986 and 1996-97 but no increase in clinical incidence of alveolar hydatid disease.
Abstract: We investigated a focus of highly endemic Echinococcus multilocularis infection to assess persistence of high endemicity in rural rodents, explore potential for parasite transmission to domestic carnivores, and assess (serologically) putative exposure versus infection frequency in inhabitants of the region. From spring 1993 to spring 1998, the prevalence of E. multilocularis in rodents was 9% to 39% for Arvicola terrestris and 10% to 21% for Microtus arvalis. From June 1996 to October 1997, 6 (7%) of 86 feral dogs and 1 of 33 cats living close to the region tested positive for intestinal E. multilocularis infection. Testing included egg detection by coproscopy, antigen detection by enzyme-linked immunosorbent assay (ELISA), and specific parasite DNA amplification by polymerase chain reaction. Thus, the presence of infected domestic carnivores can increase E. multilocularis exposure risk in humans. A seroepidemiologic survey of 2,943 blood donors in the area used specific Em2-ELISA. Comparative statistical analyses of seroprevalence and clinical incidence showed an increase in Em2-seroprevalence from 1986 and 1996-97 but no increase in clinical incidence of alveolar hydatid disease.

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TL;DR: In this paper, a Minority Game based model of a financial market where adaptive agents (the speculators) interact with deterministic agents (called producers) is presented, and transitions between equilibrium and out of equilibrium behavior are observed when the relative number of speculators to the complexity of information or to the number of producers are changed.
Abstract: We present and study a Minority Game based model of a financial market where adaptive agents—the speculators—interact with deterministic agents—called producers. Speculators trade only if they detect predictable patterns which grant them a positive gain. Indeed the average number of active speculators grows with the amount of information that producers inject into the market. Transitions between equilibrium and out of equilibrium behavior are observed when the relative number of speculators to the complexity of information or to the number of producers are changed. When the system is out of equilibrium, stylized facts arise, such as fat tailed distribution of returns and volatility clustering. Without speculators, the price follows a random walk; this implies that stylized facts arise because of the presence of speculators. Furthermore, if speculators abandon price taking behavior, stylized facts disappear.

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TL;DR: It is proposed that Rad50, an SMC‐like protein, promotes the use of the sister chromatid as the template for homologous recombinational repair, and functions in the same pathway for the repair of MMS‐induced damage as Rad21, the homologue of the Saccharomyces cerevisiae Scc1 cohesin protein.
Abstract: To study the role of Rad50 in the DNA damage response, we cloned and deleted the Schizosaccharo myces pombe RAD50 homologue The deletion is sensitive to a range of DNA-damaging agents and shows dynamic epistatic interactions with other recombination?repair genes We show that Rad50 is necessary for recombinational repair of the DNA lesion at the mating-type locus and that rad50 shows slow DNA replication We also find that Rad50 is not required for slowing down S phase in response to hydroxy urea or methyl methanesulfonate (MMS) treatment Interestingly, in rad50 cells, the recombination frequency between two homologous chromosomes is increased at the expense of sister chromatid recombination We propose that Rad50, an SMC-like protein, promotes the use of the sister chromatid as the template for homologous recombinational repair In support of this, we found that Rad50 functions in the same pathway for the repair of MMS-induced damage as Rad21, the homologue of the Saccharomyces cerevisiae Scc1 cohesin protein We speculate that Rad50 interacts with the cohesin complex during S phase to assist repair and possibly re-initiation of replication after replication fork collapse

Journal ArticleDOI
TL;DR: Different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers, even if a short-term effect of smoking prior to the experiment cannot be excluded.
Abstract: Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.

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TL;DR: It is shown that amphetamine may also excite dopamine neurons through modulation of glutamate neurotransmission, and may enhance phasic release of dopamine, which is important in the neural processing of reward.
Abstract: Amphetamine is a highly addictive psychostimulant that promotes the release of the catecholamines dopamine and norepinephrine. Amphetamine-induced release of dopamine in the midbrain inhibits the activity of dopamine neurons through activation of D2 dopamine autoreceptors. Here we show that amphetamine may also excite dopamine neurons through modulation of glutamate neurotransmission. Amphetamine potently inhibits metabotropic glutamate receptor (mGluR)-mediated IPSPs in dopamine neurons, but has no effect on ionotropic glutamate receptor-mediated EPSCs. Amphetamine desensitizes the mGluR-mediated hyperpolarization through release of dopamine, activation of postsynaptic alpha1 adrenergic receptors, and suppression of InsP3-induced calcium release from internal stores. By selectively suppressing the inhibitory component of glutamate-mediated transmission, amphetamine may promote burst firing of dopamine neurons. Through this mechanism, amphetamine may enhance phasic release of dopamine, which is important in the neural processing of reward.